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Biomedical subjects

Lian Zhang

Publications and source records attributed to Lian Zhang.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Correlation of polymorphisms of UDP-glucuronosyltransferase 1A7 gene to genetic susceptibility of lung cancer].

BACKGROUND & OBJECTIVE: UDP-glucuronosyltransferase 1A7 (UGT1A7) plays an important role in detoxification through catalyzing combination of glucuronic acid and tobacco carcinogens, including benzo [alpha] pyrene, nitrosamine, and heterocyclic amine PhIP, therefore, inactivates the carcinogens. This study was to examine the correlation of polymorphisms of UGT1A7 gene to genetic susceptibility of lung cancer. METHODS: Polymorphisms of UGT1A7 gene at 12-131 and 208 sites in peripheral lymph cells of 312 patients and 317 age- and sex-matched controls were detected by polymerase chain reaction-denaturized high performance liquid chromatography (PCR-DHPLC) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP); the correlation of these polymorphisms to genetic susceptibility of lung cancer was analyzed. RESULTS: Compared with the UGT1A7*1/*1 genotype carriers, the UGT1A7*3/*1 genotype carriers had a 1.80-fold increased risk of lung adenocarcinoma [adjusted odds ratio (OR), 1.80; 95% confidence interval (CI), 1.03-3.12], the UGT1A7*3 genotype carriers had a 1.59-fold increased risk of lung adenocarcinoma (adjusted OR, 1.59; 95% CI, 0.96-2.63). The UGT1A7 polymorphisms had no correlation with risk of lung squamous cell carcinoma. CONCLUSION: UGT1A7 gene polymorphisms may increase the genetic susceptibility of lung adenocarcinoma in Chinese.

Adenocarcinoma↗
PubMed2004

Genetic polymorphisms of interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor {alpha} and risk of gastric cancer in a Chinese population.

Helicobacter pylori infection and the cytokine-mediated inflammatory responses play important roles in gastric cancer pathogenesis. This case control study was conducted to assess the association between genetic polymorphisms in interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor alpha (TNFalpha), which are involved in H.pylori infection, and risk of gastric cancer. Genotypes were determined by PCR-based denaturing high-performance liquid chromatography analysis and direct DNA sequencing in 250 incident cases with gastric cancer and 300 controls recruited in Northern China. Serum levels of anti-H.pylori IgG and IgA were measured by enzyme-linked immunosorbent assay to indicate H.pylori infection. We found that the risk of gastric cancer was significantly elevated in subjects with the IL-8-251 AA [adjusted odds ratio (OR) 2.02; 95% confidence interval (CI) 1.27-3.21] or IL-10-1082 G (OR 2.02; 95% CI 1.24-3.29) or TNFalpha-308 AG (OR 1.81; 95% CI 1.04-3.14) genotype. An elevated risk of gastric cancer was observed in subjects with H.pylori infection and the IL-8-251 AA genotype (OR 2.54; 95% CI 1.38-4.72) or IL-10-1082 G carriers (OR 2.62; 95% CI 1.42-4.93). An increased OR was also suggested for IL-1B-31 and TNFalpha-238, but confidence intervals included the null value. There was no evidence of increased risk for any of the other polymorphisms evaluated. These findings suggest that genetic polymorphisms in IL-8, IL-10 and TNFalpha may play important roles in developing gastric cancer in the Chinese population.

Adult↗
PubMed2004

CDH1 germline mutation in hereditary gastric carcinoma.

This paper provides a bird's-eye view both in preclinical and clinical aspects of E-cadherin germline gene (CDH1) in gastric cancer patients and their families. E-cadherin, a product of CDH1 gene, belonging to the functionally related trans-membrane glycoprotein family, is responsible for the Ca(2+)-dependent cell-cell adhesion mechanism and contributes to dissociation followed by acquisition of cell motility, which usually occurs in the first step of cancer invasion and metastasis. CDH1 gene germline mutation is common in many types of carcinoma, and occurs very frequent in hereditary gastric carcinoma (HGC) patients and their families. Recently, more and more researches support that E-cadherin plays an important role in the differentiation, growth and invasion of HGC. So it is of great value to clarify its mechanisms both for understanding HGC pathogenesis and for clinical therapy, especially in China, where there are a high risk population of gastric cancer and a high HGC incidence rate. In this paper, recent researches on CDH1 gene mutation, especially its role in tumor genesis and progress of HGC, are reviewed, and advances in evaluation of its mutation status for HGC diagnosis, therapy and prognosis, are also discussed briefly.

Cadherins↗
PubMed2004

Detection of frameshift mutations of RIZ in gastric cancers with microsatellite instability.

AIM: To study the frameshift mutations of the retinoblastoma protein-interacting zinc finger gene RIZ in gastric cancer with microsatellite instability, and to identify two coding polyadenosine tracts of RIZ. METHODS: Frameshift mutations at (A)8 and (A)9 tracts of RIZ were detected in 70 human gastric cancer (HGC) specimens by DHPLC and DNA sequencing. Microsatellite instability (MSI) status was assessed by two mononucleotide markers, BAT26 and BAT25, by means of denaturing high-performance liquid chromatography (DHPLC). RESULTS: In 70 HGC samples, 8 (11.4%) were found positive for instabilities at BAT26 and BAT25. In 7 of the 8 cases with instabilities at both BAT26 and BAT25 (MSI-H), 1 was unstable at BAT26 but stable at BAT25. Frameshift mutations were identified in 4 (57.1%) of the 7 samples with MSI-H in the (A)9 tract of RIZ without mutations in the (A)8 tract. In contrast, frameshift mutations were found in neither of the polyadenosine tracts in 63 samples of MSI-L or MSI stable tumors. Pro704 LOH detection in 4 cases with frameshift mutations did not find LOH in these cases. CONCLUSION: Frameshift mutations of RIZ may play an important role in gastric cancers with MSI.

DNA-Binding Proteins↗
PubMed2004

Functional allelic heterogeneity and pleiotropy of a repeat polymorphism in tyrosine hydroxylase: prediction of catecholamines and response to stress in twins.

Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, has a common tetranucleotide repeat polymorphism, (TCAT)(n). We asked whether variation at (TCAT)(n) may influence the autonomic nervous system and its response to environmental stress. To understand the role of heredity in such traits, we turned to a human twin study design. Both biochemical and physiological autonomic traits displayed substantial heritability (h(2)), up to h(2) = 56.8 +/- 7.5% (P < 0.0001) for norepinephrine secretion, and h(2) = 61 +/- 6% (P < 0.001) for heart rate. Common (TCAT)(n) alleles, particularly (TCAT)(6) and (TCAT)(10i), predicted such traits (including catecholamine secretion, as well as basal and poststress heart rate) in allele copy number dose-dependent fashion, although in directionally opposite ways, indicating functional allelic heterogeneity. (TCAT)(n) diploid genotypes (e.g., [TCAT](6)/[TCAT](10i)) predicted the same physiological traits but with increased explanatory power for trait variation (in contrast to allele copy number). Multivariate ANOVA documented genetic pleiotropy: joint effects of the (TCAT)(10i) allele on both biochemical (norepinephrine) and physiological (heart rate) traits. (TCAT)(6) allele frequencies were lower in normotensive twins at genetic risk of hypertension, consistent with an effect to protect against later development of hypertension, and suggesting that the traits predicted by these variants in still-normotensive subjects are early, heritable, "intermediate phenotypes" in the pathogenetic scheme for later development of sustained hypertension. We conclude that common allelic variation within the tyrosine hydroxylase locus exerts a powerful, heritable effect on autonomic control of the circulation and that such variation may have implications in later development of cardiovascular disease traits such as hypertension.

Adenine↗
PubMed2004

Methylation of p16 CpG islands associated with malignant transformation of gastric dysplasia in a population-based study.

PURPOSE: Inactivation of p16 by aberrant methylation of CpG islands is a frequent event in carcinomas and precancerous lesions of various organs, including the stomach. The aim of this study is to investigate the relationship between p16 methylation and malignant transformation of human gastric dysplasia (DYS) based on follow-up endoscopic screening in a high-risk population. EXPERIMENTAL DESIGN: Genomic DNA samples were extracted from paraffin blocks of gastric mucosal biopsies that were histopathologically diagnosed as low-grade DYS from patients who developed gastric carcinomas [GCs (n = 21)] and those that did not do so (n = 21) during 5 years of follow-up. The methylation status of p16 CpG islands of each sample was detected by methylation-specific PCR, denatured high-performance liquid chromatography, and sequencing. RESULTS: Aberrant p16 methylation was observed in 5 of 21 samples of DYS that progressed to GC but in 0 of 21 samples that did not progress to GC (P = 0.048, two-sided). Sequencing results confirmed that all CpG sites were methylated in the analyzed sequence from these five p16-methylated cases. Furthermore, p16 methylation was also observed in the five subsequent GCs. Unmethylated p16 CpG islands were detected in all of the samples without p16 methylation. CONCLUSIONS: Our findings suggest p16 methylation is correlated with the malignant transformation of gastric DYS, and p16 methylation might be a useful biomarker for prediction of malignant potential of gastric DYS.

Adult↗
PubMed2004

Alteration of the ATM gene occurs in gastric cancer cell lines and primary tumors associated with cellular response to DNA damage.

Ataxia telangiectasia mutated (ATM) is the gene mutated in the genetic disorder ataxia telangiectasia (AT), the symptoms of which include sensitivity to radiation and an increased risk of cancer. ATM is a kinase involved in activating the appropriate damage-response pathway, leading to either cell-cycle arrest or apoptosis, and is therefore a key checkpoint molecule in regulating cell-cycle response to DNA damage and responsible for maintenance of genome integrity. However, little is known about the association of ATM mutations with human gastric cancer (HGC). In order to determine the mutation and mRNA expression changes of the ATM gene in HGC, we performed analyses by denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and RT-PCR technique on 13 human gastric tumor cell lines and 30 cases of fresh tumor specimens matched normal tissue. We compared the potential effect of the ATM gene mutation and cell behavior including cell-cycle arrest and induction of apoptosis in the tumor cell lines MGC803 and BGC823 with and without ionizing radiation (IR) exposure. Our data show that frequent variations were observed at 10 exons and 2 cDNA fragments which covered 8 other exons of the ATM gene as 5 out of 13 on the cell lines (38.5%) and 2 out of 30 cases in the tissue specimens (6.7%). All point mutations were confirmed as base substitutions (5982T-C; 6620A-G; 8684G-G/A; 9389C-G) and deletions (1079delC) by use of DNA sequencing. Among the mutations, one was reported previously in breast cancer, the other five have not yet been reported. The expression of ATM was significantly lower in five cell lines (MGC803; MKN45; SGC7901; GES and SUN-1) than in two others (BGC823 and RF48). G2/M cell-cycle arrest and apoptosis were observed in ATM-deficient MGC803 cells challenged with IR. A transient up-regulation of p53 occurred 1h post-IR in BGC823 cells but not in MGC803 cells. Our findings suggest that ATM mutations might be a pathogenic factor for an increased risk of gastric cancer, and the dysfunction of ATM may lead to a hypersensitivity to ionizing radiation in gastric cancer cells, possibly by a p53-dependent pathway.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2004

Methylmalonic acid in amniotic fluid and maternal urine as a marker for neural tube defects.

To evaluate the implication of methymalonic acid (MMA) in the early diagnosis of neural tube defects (NTD), a quantitative assay for MMA was established by using gas chromatography-mass spectrometry with stable isotope of MMA as an internal standard. Amniotic fluid and maternal urine MMA concentration, maternal serum folate, red blood cell folate and vitamin B12 levels were measured in the middle term of NTD-affected and normal pregnancies. Amniotic fluid and maternal urine MMA concentrations in the middle term of NTD affected pregnancies (1.4 +/- 0.9 micromol/L, and 22.1 +/- 12.6 nmol/micromol creatinine) were significantly higher than that of normal pregnancies (1.0 +/- 0. 4 micromol/L, and 2.5 +/- 1.1 nmol/micromol creatinine). There was no significant difference between normal and NTD pregnancies for serum folate, red blood cell folate and vitamin B12 levels. The results suggested that MMAs in amniotic fluid and maternal urine are sensitive markers for early diagnosis of NTD. Vitamin B12 is an active cofactor involved in the remethylation of homocycteine and its deficiency is an independent risk factor for NTD. MMA is a specific and sensitive marker for intracellular vitamin B12 deficiency. This study suggests that it is necessary to monitor the vitamin B12 deficiency and advocates vitamin B12 supplementation with folate prevention program.

Adult↗
PubMed2004

Efficacy of intramuscular matrine in the treatment of chronic hepatitis B.

BACKGROUND: Hepatitis B virus (HBV) infection, a global public health problem, is the leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. There are more than 350 million HBV carriers in the world and up to one million die annually due to hepatitis B associated liver disease. So far no optimal treatment is available for patients with chronic hepatitis B. In the paper we investigated the efficacy of intramuscular matrine in the treatment of chronic hepatitis B. METHODS: One hundred and twenty patients with chronic hepatitis B were randomly divided into matrine treatment group (n=60) and control group (n=60). The patients of the matrine group were given intramuscularly with matrine (an alkaloid extracted from a traditional Chinese herb Radix Sophorae Flavescentis by Guangzhou Ming Xing Pharmaceutical Factory, Guangzhou, China) of 100 mg daily for 90 days in addition to conventional liver-protective drugs including glucurone, inosine, compound vitamin B and caryophyllin. The control group received conventional liver-protective drugs alone. Clinical manifestations and laboratory parameters including liver biochemistry and serum hepatitis B virus markers were monitored before and after treatment in the two groups. RESULTS: Significant differences were seen between the two groups in terms of improvement of clinical symptoms and signs, recovery of liver functions, and serum conversion from hepatitis Be antigen to HBe antibody and from positive to negative serum HBV DNA (P<0.05-0.01). The result of the matrine group was more marked than that of the control group. Serious side-effects were not observed except mild pain at the site of injection of matrine in a few patients. CONCLUSION: These results indicate that intramuscular matrine may be an economical, efficacious, safe drug for the treatment of chronic hepatitis B.

Adult↗
PubMed2004

[Studies of the relationship of HLA polymorphisms and the infection of H. pylori in the population of Linqu in Shandong Province].

In order to analyze the relationship of HLA polymorphisms and the infection of H. pylori in the population of Linqu County in Shandong Province, polymerase chain reaction with sequence-specific primers(PCR-SSP) was used to determine the alleles of HLA type I and II in 90 Hp-positive persons and 49 Hp-negative controls. The results showed that among the 68 alleles of HLA type I ,4 alleles were found significantly different between Hp-positive and Hp-negative population,while no significant difference was found among the 22 alleles of HLA type UI. Hp-positive persons had a lower allele frequency of A* 02 (OR=0.56, 95% CI=0.33 approximately 0. 94; P=0.029), B* 48 (OR=0.15, 95% CI=0.03 approximately 0.72; P=0. 007), CW* 08 (OR=0. 32, 95% CI=0.15 approximately 0.69; P=0. 003) and a higher allele frequency of CW* 15 (OR=5.11, 95% CI=0.63 approximately 40.90; P=0. 024) compared with Hp-negative controls. Our results indicated that the polymorphisms of HLA type I is involved in the genetic susceptibility of Hp infection in Linqu County,while the polymorphisms of HLA type I may have no relationship with the genetic susceptibility of Hp infection. It was shown that among the alleles of HLA type I , CW* 15 might be a susceptible gene of Hp infection while A * 02 ,B * 48 and CW* 08 might be protective genes.

Aged↗
PubMed2003

[Correlation between polymorphisms of interleukin-1beta and RN genes and risk of gastric carcinoma: a case-control study].

OBJECTIVE: To investigate the correlation between polymorphisms of interleukin-1beta and RN genes and risk of gastric carcinoma. METHODS: PCR and denaturing high-performance liquid chromatography (DHPLC) were used to analyze the IL-1beta-31 and -511 C/T polymorphisms and to genotype the IL-1RN penta-allelic variable number of tandem repeats (VNTR): of the DNA from the peripheral blood of 143 patients of gastric carcinoma, 97 from Linqu County, Shandong Province, and 46 cases from the specimen bank of Beijing Cancer Hospital, and 337 controls without gastric carcinoma from Linqu County, most of which suffered from other gastric diseases. RESULTS: IL-1-511 polymorphisms (carriers of IL-1beta-511T) were correlated with the increased risk of interstitial gastric carcinoma in both sexes (OR = 3.833, 95% CI: 2.282 approximately 6.439) and increased risk of diffuse gastric carcinoma in males (OR = 3.464, 95% CI: 1.394 approximately 8.608). The frequencies of IL-1beta-31 polymorphisms and IL-1IRN VNTR were not different between the gastric carcinoma group and the control group, IL-1beta-511 T carrier could be seen in the controls at different precancerous stages, for chronic atrophic gastritis (OR = 5.164, 95% CI: 2.661 approximately 10022), for interstitial metaplasia (OR = 5.093, 95% CI: 2.708 approximately 9.463), and for dysphasia (OR = 8.438, 95% CI: 3.939 approximately 18.073). CONCLUSION: IL-1beta-31 genotypes and. IL-2RN VNTR do not increase the risk of gastric carcinoma. The IL-1beta-511 T genotype increases the risk of gastric carcinoma in every precancerous stage.

Alleles↗
PubMed2003

The effects of bilirubin on evoked potentials and long-term potentiation in rat hippocampus in vivo.

Neonatal jaundice is a common condition that could potentially lead to severe neurotoxicity. In this electrophysiological study we observed the effects of a short-term bilirubin injection on evoked potentials (population spike, PS) and long-term potentiation (LTP) in the hippocampal CA3 region of Sprague Dawley rats in vivo. The animal received a bolus i.v. injection of either 60 mg/kg, or 30 mg/kg of bilirubin, or an equivalent volume of bilirubin-free vehicle in 5 min. The results showed that both bilirubin-treated groups had a dose-independent prolongation of peak latencies and decrease of slopes of the PS at all measured time points following injection (1, 3, 5, 10, 15, 30, 45, 60, 90, 120 min), while the amplitudes of the PS did not change significantly. The peak latency, slope, and the amplitude of PS stayed unchanged in the control group. Furthermore, while LTP could be induced by high-frequency stimulation in control animals, this phenomenon was absent in both bilirubin-treated groups. The amplitudes of the PS in the two treated groups after stimulation were also smaller than those of the control animals at every time points. These findings are in accordance with previous observations showing significant depressive effects of bilirubin on the nervous system. Our novel finding that short-term exposure to bilirubin can inhibit the induction of LTPs in the hippocampus, is compatible with the suggestion that neonatal hyperbilirubinemia can impact on learning and memory.

Animals↗
PubMed2003

High throughput detection of microsatellite instability by denaturing high-performance liquid chromatography.

Microsatellite instability (MSI) is a hallmark of the DNA replication error phenotype, due to the inactivation of mismatch repair genes. MSI has been implicated in colon and many other gastrointestinal cancers. MSI usually can be analyzed by PCR amplification of microsatellite markers followed by electrophoresis and detected using autoradiography or fluorescence techniques. We report here a novel method for high-throughput detection of MSI using denaturing high performance liquid chromatography (DHPLC). Amplification of two mononucleotide markers (BAT25 and BAT26) by polymerase chain reaction (PCR) is followed by DHPLC analysis to display alteration in the length of repetitive sequences. These two markers were tested in 84 colorectal cancer samples confirmed to be 44 MSI-H and 40 MSI-L or MSS, previously defined by multiple microsatellite markers and/or by immunohistochemical analyses of MLH1 and MSH2 proteins. Among 44 MSI-H samples, sequence variations in BAT26 and BAT25 were detected in 44 (100%) and 43 (98%), respectively, while no sequence variation in the two markers was detected in 40 MSI-L or MSS samples. A total of 96 gastric cancers and their matched normal tissues were then analyzed for MSI-H using this method. Sequence variations in BAT26 and BAT25 were detected in nine (9.4%) samples. Seven of the nine cases were shown unstable at both BAT26 and BAT25; one each was unstable at BAT26 or BAT25. These results were confirmed by autoradiography analyses. Together, our results demonstrate high sensitivity and specificity of DHPLC in the analysis of sequence variations in BAT25 and BAT26 to determine MSI status. This simple, efficient, and high-throughput approach will facilitate analysis of MSI in large sample sets of any cancers.

Chromatography, High Pressure Liquid↗
PubMed2003

Loss of striatal vesicular monoamine transporter protein (VMAT2) in human cocaine users.

OBJECTIVE: The hypothesis that human cocaine users lose vesicular monoamine transporter (VMAT2) protein was tested in striatal samples from cocaine users and age-, sex-, and postmortem interval-matched comparison subjects. METHOD: Striatal samples were retrieved at autopsy; immunoblot assays were then performed by using a highly specific VMAT2 antibody. Striatal radioligand binding to VMAT2 was assessed with dihydrotetrabenazine ([(3)H]DTBZ) and dopamine levels employing high-performance liquid chromatography. RESULTS: Cocaine users displayed a marked reduction in VMAT2 immunoreactivity as well as reduced [(3)H]DTBZ binding and dopamine levels. It did not appear that the reduction in VMAT2 immunoreactivity was related to ethanol use, but dopamine levels were lower in subjects with only ethanol diagnoses. Subjects suffering from cocaine-induced mood disorders displayed a greater loss of VMAT2 immunoreactivity that approached significance. CONCLUSIONS: Human cocaine users lose VMAT2 protein, which might reflect damage to striatal dopamine fibers. These neuronal changes could play a role in causing disordered mood and motivational processes in more severely dependent patients.

Adolescent↗
PubMed2003

Anti-Helicobacter pylori immunoglobulin G (IgG) and IgA antibody responses and the value of clinical presentations in diagnosis of H. pylori infection in patients with precancerous lesions.

AIM: To determine the prevalence of Helicobacter pylori (H. pylori) infection, the serum anti-H. pylori immunoglobulin G (IgG) and IgA antibody responses, and the value of clinical presentations in diagnosis of H. pylori infection in patients with gastric atrophy, intestinal metaplasia and dysplasia. METHODS: H. pylori infection was detected by histology in 209 patients with mild chronic atrophic gastritis (CAG, n=76), severe CAG (n=22), mild intestinal metaplasia (IM, n=22), severe IM (n=58), or dysplasia (DYS, n=31). Serum anti-H. pylori IgG and IgA were double sampled and evaluated by enzyme-linked immunoadsordent assays. 35 clinical presentations were observed and their relationship with H. pylori infection was analyzed by the k-means cluster method. RESULTS: Both IgG and IgA levels in H. pylori positive patients were significantly higher than those negative for H. pylori (P<0.001-0.01). The prevalence of H. pylori was highest in severe IM (84.5 %), and lowest in mild CAG (51.3 %) (P<0.01). They were similar in severe CAG (68.2 %), mild IM (72.7 %), and DYS (67.7 %). In H. pylori positive patients, the IgG levels in severe CAG were significantly higher than those in mild CAG (P<0.01). In H. pylori negative patients, both IgG and IgA levels increased remarkably in severe IM, compared to those in mild IM (P<0.01-0.05). H. pylori infection exhibited no association with patient's gender (62.1 % in males; 71.7 % in females) and age (r=0.0814, P=0.241). The diagnostic accuracy based on 35 clinical presentations was 65.7 %. It could be improved by 5.7 % when only the assemblage of digestive symptoms were engaged, or by 8.6 % when the pathogenic factors, general status and grossoscopy were combined. The diagnostic accuracy could be decreased when only the general symptoms were engaged, or when the pathogenic factors were accompanied with some common digestive symptoms. CONCLUSION: H. pylori infection is a major risk factor for the process from atrophy, IM to DYS of gastric mucosa. Serum IgG and IgA are good indicators to evaluate this progress with a certain arrearage. Investigation on the effective assemblages of clinical presentations may provide a better understanding in the pathogenesis, diagnosis and treatment for H. pylori infection.

Aged↗
PubMed2003

[Screening and evaluation of non-invasive diagnosis markers for compensated liver cirrhosis in patients with chronic hepatitis B].

OBJECTIVE: To evaluate the diagnostic value of liver fibrosis markers and ultrasonic examination for determining compensated liver cirrhosis in patients with chronic hepatitis B, and screen applicable non-invasive diagnostic marker for compensated liver cirrhosis. METHODS: Serum hyaluronic acid (HA), Type III procollagen (PCIII), laminin (LN) and Type IV collagen (CIV) were measured from 350 patients with chronic hepatitis B, who were also detected with liver biopsy and ultrasonography. To determine the cut-off value of every serum liver fibrosis marker for diagnosing compensated liver cirrhosis, data was analysed with clinical epidemiology methods. Then evaluated and compared all the markers. RESULTS: 85 out of 350 patients were diagnosed as compensated liver cirrhosis by liver biopsy, and 81 had liver cirrhosis images by ultrasonic examination. HA achieved the biggest area under the ROC curve. The cut-off values with best sensitivity and accuracy of HA, PCIII, LN and CIV were 154.35 microg/L, 198.44 microg/L, 137.58 microg/L and 100.80 microg/L respectively. The related diagnostic sensitivities of HA, PCIII, LN and CIV were 82.4%, 63.5%, 57.3% and 70.6%, specificities were 79.3%, 54.0%, 56.8%, 68.3%, and accuracies were 80.0%, 56.3%, 56.9%, 68.9%, respectively. Parallel tests could increase the diagnostic sensitivity, but decreased specificity and accuracy accordingly. Compared with other non-invasive diagnostic methods, HA was the best marker (mu > or =1.814, P<0.05). The level of HA at 119.17 microg/L was suitable for determining compensated cirrhosis, with a 87.1% sensitivity, 67.6% specificity, 72.3% accuracy, 46.25% positive predictive value and 94.7% negative predictive value. CONCLUSION: Among the non-invasive serum diagnostic markers for liver fibrosis and ultrasonic examination for cirrhosis image, HA is the best marker for diagnosing compensated liver cirrhosis.

Adolescent↗
PubMed2003

[Analysis of three lamivudine-resistant HBV mutants with the method of restriction enzyme digestion and its application].

OBJECTIVE: To investigate the prevalence of three lamivudine-resistant HBV mutants in lamivudine-treated Chinese patients. METHODS: Using three pairs of of HBV polymerase gene B and C domain fragments were amplified by PCR. The PCR products were then digested by restriction enzyme Nde I and Nla III. The digested products were analyzed by electrophoresis. With this method, the prevalence of the three lamivudine-resistant mutants in lamivudine-treated Chinese patients was investigated. RESULTS: After Nde I digestion of p24 and p29 amplified product, HBV wild type could be easily separated from YMDD mutant. At the same time, YIDD could be separated from YVDD mutant after Nla III digestion of p24 and p29 amplified product. By this method, the authors found that these eleven patients were infected with lamivudine-resistant mutants. Six of them were infected with M5501 mutant; five were infected with M550V mutant (one of them had both M550V and L526M mutations). CONCLUSION: The method of the present study was demonstrated to be an easy way to detect HBV lamivudine-resistant mutants and can be applied to clinical monitoring of lamivudine resistance.

Adolescent↗