Clinicopathological and prognostic significance of MUC4 expression in cancers: evidence from meta-analysis.

Mucin4 (MUC4) is a secreted glycoprotein. Numerous studies had indicated that MUC4 was an attractive prognostic tumor biomarker. However, the results of different studies have been inconsistent. So we conducted this meta-analysis to explore the association between MUC4 expression and cancer prognosis. A systematically comprehensive search was performed through PubMed, EMBASE and CNKI (Chinese National Knowledge Infrastructure). Prognostic value of MUC4 expression in malignancy patients was evaluated by pooled hazard ratios (HRs) and their 95% confidence intervals (CIs). Meanwhile, pooled odds ratio (OR) with 95% CI was appropriate for the association between MUC4 expression and clinicopathological parameters. Eighteen studies including 1,933 patients were enrolled in this meta-analysis. Significant association was found between elevated MUC4 expression and poorer overall survival (OS) with pooled hazard ratio (HR) of 1.87 [95% confidence interval (CI): 1.58-2.23, P<0.001]. Significant associations were also detected in biliary tract carcinoma (HR: 2.41, 95% CI: 1.69-3.42, P<0.001), pancreatic cancer (HR: 2.01, 95% CI: 1.42-2.86, P<0.001) and colorectal cancer (HR: 1.73, 95% CI: 1.17-2.54, P=0.006). Moreover, combined odds ratio (OR) of MUC4 indicated that MUC4 overexpression was associated with tumor stage, tumor invasion and lymph node metastasis. Our results demonstrated that MUC4 may be exploited as a novel prognostic biomarker for cancer patients.

Gestational thyroid reference intervals in antibody-negative Chinese women.

OBJECTIVES: The aim of this study is to establish gestation-specific reference intervals (GRIs) for thyroid function assays in pregnant Chinese women with ARCHITECT and compare them to other GRI studies. DESIGN AND METHOD: Thyroid antibody negative pregnant Chinese women were enrolled and followed to establish GRIs for thyroid function by use of the Abbott ARCHITECT i2000SR analyzer (N=1409). Samples from 360 non-pregnant Chinese women served as controls. RESULTS: GRIs of thyroid-stimulating hormone, free thyroxine and free triiodothyronine for first trimester pregnancies were 0.16-3.78mIU/L, 10.9-17.7pmol/L and 2.9-5.0pmol/L, respectively. GRIs for second trimester pregnancies were 0.34-3.51mIU/L, 9.3-15.2pmol/L and 2.9-4.6pmol/L. GRIs for third trimester pregnancies were 0.34-4.32mIU/L, 7.9-14.1pmol/L and 2.9-4.5pmol/L. CONCLUSIONS: Our thyroid GRIs were different from those in other Chinese studies generated on other analyzers, but were similar to a Swiss study using the same analyzer. These data should prove useful for the interpretation of thyroid function assays among pregnant women measured on the Abbott analyzer.

Novel real-time PCR assay for rapid prenatal diagnosis of Down syndrome: a prospective study of 563 amniocytes.

OBJECTIVE: To explore the possibilities of a novel real-time PCR assay for rapid prenatal diagnosis of Down syndrome in clinical settings. DESIGN AND METHODS: This duplex real-time PCR assay is based on relative quantification of DSCR4 gene on chromosome 21 by using RABIF gene on chromosome 1 as a reference. For each sample, the differences in threshold cycles between DSCR4 and RABIF genes (Delta Ct, DeltaCt) were detected, and a calibrated DeltaCt value (DeltaDeltaCt, DeltaCt (sample)-DeltaCt (internal control)) was analyzed. Overall, 563 amniotic fluid samples from patients were blindly tested for fetal chromosome analysis and their DeltaDeltaCt values were evaluated according to the karyotyping results. RESULTS: Chromosome analysis revealed that 12 fetuses had trisomy 21 and 551 others were normal in chromosome 21. The DeltaDeltaCt values of trisomy 21 fetuses were significantly lower than those of normal ones (p-value<0.001) and no overlapping was shown: lower than -0.49 for trisomy 21 and above -0.30 for a normal one. CONCLUSIONS: DeltaDeltaCt value could be used as a direct diagnostic index in real-time PCR assay; this novel assay is applicable for rapid prenatal diagnosis of Down syndrome in clinical settings.

[Second trimester maternal serum screening for Down's syndrome in women of advanced maternal age: a multi-center prospective study].

OBJECTIVE: To evaluate the performance characteristics of the second trimester double test for the detection of fetal Down's syndrome (DS) in women of advanced maternal age (AMA). METHODS: We undertook a prospective nation-wide multi-centered study and chose alpha-fetoprotein (AFP) and free beta-subunit of human chorionic gonadotrophin (free beta-hCG) as the serum markers. Between May 2004 and September 2006, 12 centers participated in the collection and analysis of maternal serum AFP and free beta-hCG. Patients with an increased risk of DS (> or = 1/270) were offered genetic amniocentesis. Follow up of the outcome of all pregnancies was obtained. Patients were divided into two groups, the AMA group and the non-AMA group and the screening efficiency was evaluated in both groups. RESULTS: A total of 66 132 singleton pregnancies were included in the study, and there were 3610 (5.46%) AMA women. The median maternal age of AMA women was 36.8years (35 - 47 years). At a cut-off of 1/270, in the AMA group, the number of positive cases screened was 727 and 22 cases of fetal DS were detected; the number of negative cases screened was 2883, and no fetal DS was found. In the non-AMA group, the number of positive cases screened was 4743 and 69 cases of fetal DS were detected; the number of negative cases screened was 57 779, and 6 cases of fetal DS were diagnosed postnatally. In AMA group, the detection rate (DR), false positive rate (FPR) and odds of being affected given a positive result (OAPR) were 100%, 19.7% and 3.0% respectively. In the non-AMA group, the DR, FPR and OAPR were 92.0%, 7.5% and 1.5% respectively. CONCLUSION: The double-marker test using AFP and free beta-hCG is an effective screen strategy for second-trimester detection of Down syndrome in AMA women.

[Second trimester maternal serum screening for Down's syndrome in mainland China: a multi-center prospective study].

OBJECTIVE: To evaluate the performance characteristics of the second trimester double-marker test for the detection of fetal Down's syndrome in mainland China. METHODS: This prospective national multi-centered study used alpha-fetoprotein (AFP) and free beta-subunit of human chorionic gonadotrophin (free beta-hCG) as the serum markers. From May 2004 to September 2006, 11 centers participated in the collection and analysis of maternal serum AFP and free beta-hCG between 14 and 20(+6) weeks of pregnancy. The screening results were calculated using the standard algorithm based on the standard database provided with the analytic software. Patients with an increased risk of Down's syndrome pregnancy (> or = 1/270) were offered genetic amniocentesis. Outcomes of all pregnancies were obtained. RESULTS: A total of 66 132 singleton pregnancies were included in the study. The median maternal age was 27 years. At a cut-off of 1 in 270, the detection rate (DR) based on a Caucasian database was 72% corresponding to a false positive rate (FPR) of 5%, and the DR based on the Chinese database was raised to 76% corresponding to an FPR of 5%. CONCLUSION: The double-marker test using AFP and free beta-hCG is an effective screen strategy for second-trimester detection of fetal Down's syndrome in mainland China. Ethnic variance exists between the Caucasian and Chinese populations. The accuracy of screening is increased by the use of race-specific medians.

[Application of differential display-PCR technique in fluconazole-resistance gene expression of Candida].

OBJECTIVE: To investigate the application of differential display-2PCR(DD-PCR) in research on gene expression of Candida. METHODS: Resistance to fluconazole was induced in a Candida albicans isolate 435 from vagina by culturing in YEPD broth with increasing fluconazole concentration in vitro, and the resistant isolate 435-2 (MIC=128 microg/ml ) was obtained after 80 days of incubation. Comparisons between 435 and 435-2 either in fluconazole-containing medium or in drug-free medium were performed with the modified DD-PCR including amplification with long primers, silver staining, reverse dot blot and non-radiographic labeling techniques. RESULTS: Three differential displayed bands were found which showed high homology to alcohol dehydrogenase 1 (ADH1), TOP2 and CDR1, respectively. The up-regulating expression of ADH1 and CDR1 associated with fluconazole resistance was further identified by RT-PCR. CONCLUSION: The up-regulating expression of ADH1 and CDR1 was associated with fluconazole resistance in Candida albicans, ADH1 might be a candidate of novel fluconazole resistant gene.

[DNA and RNA random amplification polymorphism in 5-flurocytosine-resistant strains of Candida albicans from revul-vaginal candidasis].

OBJECTIVE: To investigate the DNA genome and RNA expression in 5-flurocytosine-resistant strains of Candida albicans from vaginal candidasis. METHODS: Sixteen strains of Candida albicans were selected from clinically diagnosed revul-vaginal candidasis. Eight 5-flurocytosine-sensitive isolates and 8 resistant isolates were examined by France Media FUNGUS sensitive test. DNA genome was detected with random amplification polymorph DNA. RNA expression was detected with random amplification polymorph RNA method. RESULTS: There were no distinct differences between 5-flurocytosine-sensitive and resistant Candida albicans in DNA genome, while RNA expression showed significant differences between 5-flurocytosine-resistant and sensitive strains. CONCLUSION: Clinical 5-flurocytosine-resistant strains of Candida albicans from revul-vaginal candidasis may be related to phenotype changes.

[Study on experimental induction of fluconazole resistance in Candida albicans].

To investigate the phenotype and genotype variation between the Fluconazole resistant C. albicans isolates and the corresponding susceptible ones, our research established a resistance-induction mode in vitro. Comparisons were done on drug resistance maintainability, metabolic profile and the doubling time in the logarithmic growth phase. Genotypes were determined by ERIC-PCR. The Fluconazole resistant isolates appeared in strain 435, A06, B07 and C01 from total 22 clinical Fluconazole susceptible isolates after being incubated for 45-80 days in YEPD broth with increasing Fluconazole concentration. The parent isolates had a same metabolic profile and a similar growth doubling time to their filial generation. The same ERIC-PCR profiles were also found between the susceptible parents and their resistant filial isolates. The resistant isolates maintained drug resistance for 24 days after growing on drug-free medium. It was supposed that candida albicans had a latent capacity to evolve resistance to azoles under a certain antifungal drug selective pressure, and the acquired resistance could maintain in drug-free media for a certain period. The resistant isolate with no adaptive cost may be prone to vogue among people. ERIC-PCR could be used in epidemiological study as a stable marker.