Circulating mRNA and microRNA profiling analysis in patients with ischemic stroke.

To provide insight into molecular diagnosis and individualized treatment of ischemic stroke (IS), several available datasets in IS were analyzed to identify the differentially expressed genes and microRNAs (miRNAs). Series matrix files from GSE22255 and GSE16561 (mRNA profiles), a well as GSE110993 (miRNA profile) were downloaded from the Gene Expression Omnibus database. System­level clustering was performed with GeneCluster 3.0 software, and gene annotation and pathway enrichment were performed with gene ontology analysis and Database for Annotation, Visualization and Integrated Discovery software. For a protein­protein interaction (PPI) network, Biological General Repository for Interaction Datasets and IntAct interaction information were integrated to determine the interaction of differentially expressed genes. The selected miRNA candidates were imported into the TargetScan, miRDB and miRecords databases for the prediction of target genes. The present study identified 128 upregulated and 231 downregulated genes in female stroke patients, and 604 upregulated and 337 downregulated genes in male stroke patients compared with sex­ and age­matched controls. The construction of a PPI network demonstrated that male stroke patients exhibited YWHAE, CUL3 and JUN as network center nodes, and in female patients CYLD, FOS and PIK3R1 interactions were the strongest. Notably, these interactions are mainly involved in immune inflammatory response, apoptosis and other biological pathways, such as blood coagulation. Female and male upregulated genes were cross­validated with another set of Illumina HumanRef­8 v3.0 expression beadchip (GSE16561). Functional item association networks, gene function networks and transcriptional regulatory networks were successfully constructed, and the relationships between miRNAs and target genes were successfully predicted. The present study identified a number of transcription factors, including DEFA1, PDK4, SDPR, TCN1 and MMP9, and miRNAs, including miRNA (miR)­21, miR­143/145, miR­125­5p and miR­122, which may serve important roles in the development of cerebral stroke and may be important molecular indicators for the treatment of IS.

A Preliminary Report of A Low-Dose Step-Up Regimen of Recombinant Human FSH for Young Women Undergoing Ovulation Induction with IUI.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of a recombinant human follicle stimulating hormone (r-FSH) low-dose step-up regimen for controlled ovarian hyperstimulation in patients undergoing ovulation induction (OI) with intrauterine insemination (IUI). MATERIALS AND METHODS: The study was conducted in the Department of Obstetrics and Gynecology, Far Eastern Memorial Hospital, New Taipei, Taiwan. In this prospective, observational study, consecutive infertile women (20-35 years) with regular menstrual cycles and a normal baseline FSH level were prospectively enrolled between January 2010 and September 2010. A starting dose of 112.5 IU/day r-FSH was administered on day 3 and increased by 37.5 IU/day every 2 days until a follicle ≥11 mm in diameter was present. Recombinant human chorionic gonadotropin (r-hCG) was administered when a follicle ≥18 mm was noted. Monifollicular development was defined as only one follicle with a diameter ≥16 mm. Clinical pregnancy was defined as a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs. RESULTS: A total of 29 women and 30 cycles were included. The mean daily dose of r-FSH to achieve a follicle of ≥11 mm in diameter was 131.3 ± 23.6 IU and the mean total dose was 1030.0 ± 383.2 IU. Approximately 41% of the cycles were monofollicular. Clinical pregnancy was observed in 9 (30.0%) cycles, and a fetal heart beat was observed in 7 (23.3%). There were no multiple pregnancies. Mild ovarian hyperstimulation syndrome, which was resolved with conservative management, was observed in 3 (10.0%) cycles. CONCLUSION: This r-FSH low-dose step-up regimen seems to be a feasible and practical method for OI in younger infertile women undergoing IUI.

The outcomes of intracytoplasmic sperm injection and laser assisted hatching in women undergoing in vitro fertilization are affected by the cause of infertility.

BACKGROUND: We sought to determine the association between factors that affected clini- cal pregnancy and live birth rates in patients who underwent in vitro fertilization (IVF) and received intracytoplasmic sperm injection (ICSI) and/or laser assisted hatching (LAH), or neither. MATERIALS AND METHODS: In this retrospective cohort study, the records of women who underwent IVF with or without ICSI and/or LAH at the Far Eastern Memorial Hospital, Taipei, Taiwan between January 2007 and December 2010 were reviewed. We divided patients into four groups: 1. those that did not receive ICSI or LAH, 2. those that received ICSI only, 3. those that received LAH only and 4. those that received both ICSI and LAH. Univariate and multivariate analyses were performed to determine factors associated with clinical pregnancy rate and live birth rate in each group. RESULTS: A total of 375 women were included in the analysis. Oocyte number (OR=1.07) affected the live birth rate in patients that did not receive either ICSI or LAH. Mater- nal age (OR=0.89) and embryo transfer (ET) number (OR=1.59) affected the rate in those that received ICSI only. Female infertility factors other than tubal affected the rate (OR=5.92) in patients that received both ICSI and LAH. No factors were found to affect the live birth rate in patients that received LAH only. CONCLUSION: Oocyte number, maternal age and ET number and female infertility fac- tors other than tubal affected the live birth rate in patients that did not receive ICSI or LAH, those that received ICSI only, and those that received both ICSI and LAH, respectively. No factors affected the live birth rate in patients that received LAH only. These data might assist in advising patients on the appropriateness of ICSI and LAH after failed IVF.

Factors associated with failure to achieve birth emphasizing a successful singleton at term following in vitro fertilization.

OBJECTIVE: To evaluate the factors that might affect birth emphasizing a successful singleton at term (BESST) outcomes in women undergoing in vitro fertilization. METHODS: A retrospective review of assisted reproduction cases from January 1, 2001, to July 31, 2005, at the Far Eastern Memorial Hospital, Taipei, Taiwan. Variables that were potentially associated with failure to achieve BESST were evaluated using univariate and multivariate logistic regression analysis. RESULTS: Successful embryo transfer occurred in 297 of the 323 cases of assisted reproduction. In total, 123 women became pregnant and were enrolled for analysis, of whom 94 had live births and 55 achieved BESST. Multivariate analysis indicated that the number of embryos transferred, the presence of ovarian hyperstimulation syndrome, female infertility factors (other than tubal factors), and embryo quality were associated with increased relative risk of BESST failure, with odds ratios of 1.02 (95% confidence interval [CI], 1.01-1.02), 1.21 (95% CI, 1.08-1.36), 1.41 (95% CI, 1.22-1.62), and 0.79 (95% CI, 0.68-0.91), respectively. CONCLUSION: The number of embryos transferred, the presence of ovarian hyperstimulation syndrome, female infertility factors other than tubal factors, and embryo quality correlate with the risk of failure to achieve BESST.

Acceleration to death from liver cancer in people with hepatitis B viral mutations detected in plasma by mass spectrometry.

Liver cancer is the leading cause of cancer death in many regions of the world. With the goal to discover biomarkers that reflect subsets of high-risk individuals and their prognosis, we nested our study in a male cohort of 5,581 hepatitis B surface antigen carriers in Qidong, People's Republic of China, who were recruited starting in 1989. By December 2003, 667 liver cancer cases were diagnosed in this group and plasma samples collected at the initial screening at enrollment were available in 515 cases who had succumbed to liver cancer. Hepatitis B virus (HBV) DNA could be isolated in 355 (69%) of these samples. In 14%, 15%, 19%, 31%, and 22%, screening took place at < or = 1.5, 1.51 to 3, 3.01 to 5, 5.01 to 9, and > 9 years before death, respectively; and 39% died at age below 45 years. The relation between mutations in HBV and time to death were determined by logistic regression for the odds of mutation and by survival analyses methods with age as the time scale. In 279 (79%) of these individuals, the samples contained a two-nucleotide 1762T/1764A HBV mutation. Sixteen samples lacking the 1762T/1764A mutation had novel mutations elsewhere in the 1761 to 1767 region of the HBV genome. There was a statistically significant difference (P = 0.012) for the high prevalence of the HBV mutations in the men who died from hepatocellular carcinoma under the age of 45 years relative to those who died after 55 years of age and HBV mutations accelerated death (relative hazard, 1.40; 95% confidence interval, 1.06-1.85) and that the effect was attenuated by age from 2.04 for age 35 years to 1.0 for age 65 years with the 90% confidence band being above 1 for ages < 50 years. These findings provide a conceptual framework to explain the acceleration of mortality in individuals infected with HBV.

Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People's Republic of China.

Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated foods, and are exposed to high levels of phenanthrene, a sentinel of hydrocarbon air toxics. Cruciferous vegetables, such as broccoli, contain anticarcinogens. Glucoraphanin, the principal glucosinolate in broccoli sprouts, can be hydrolyzed by gut microflora to sulforaphane, a potent inducer of carcinogen detoxication enzymes. In a randomized, placebo-controlled chemoprevention trial, we tested whether drinking hot water infusions of 3-day-old broccoli sprouts, containing defined concentrations of glucosinolates, could alter the disposition of aflatoxin and phenanthrene. Two hundred healthy adults drank infusions containing either 400 or < 3 micromol glucoraphanin nightly for 2 weeks. Adherence to the study protocol was outstanding; no problems with safety or tolerance were noted. Urinary levels of aflatoxin-N(7)-guanine were not different between the two intervention arms (P = 0.68). However, measurement of urinary levels of dithiocarbamates (sulforaphane metabolites) indicated striking interindividual differences in bioavailability. An inverse association was observed for excretion of dithiocarbamates and aflatoxin-DNA adducts (P = 0.002; R = 0.31) in individuals receiving broccoli sprout glucosinolates. Moreover, trans, anti-phenanthrene tetraol, a metabolite of the combustion product phenanthrene, was detected in urine of all participants and showed a robust inverse association with dithiocarbamate levels (P = 0.0001; R = 0.39), although again no overall difference between intervention arms was observed (P = 0.29). Understanding factors influencing glucosinolate hydrolysis and bioavailability will be required for optimal use of broccoli sprouts in human interventions.

Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas.

Hepatocellular carcinoma is one of the most common cancers worldwide. Infection with hepatitis B virus and exposure to aflatoxins in the diet act synergistically to amplify risk. From a public health perspective, hepatitis virus vaccination programs and efforts to both reduce aflatoxin exposures and to attenuate the toxicological consequences of unavoidable exposures should have major impacts on the global incidence of this disease. Experimentally, aflatoxin-induced hepatocarcinogenesis can be inhibited by over a score of different chemopreventive agents with multiple mechanisms of action. One agent, oltipraz, is a potent inducer of phase 2 enzymes involved in the detoxication of carcinogens including aflatoxin. A second agent, chlorophyllin, impedes the bioavailability of carcinogens by forming molecular complexes and enhances their elimination in the fecal stream. This review highlights the findings of recent randomized clinical trials with oltipraz and chlorophyllin conducted in individuals exposed to dietary aflatoxins and at high risk for development of liver cancer. Both chemopreventive agents modulated levels of aflatoxin biomarkers in the study participants in manners consonant with protection. Although pharmacological approaches establish proof of principle and help identify key molecular targets for interventions, food-based approaches that also use these molecular targets may be the most practical for widespread application in high-risk populations.

[Comparison of the yearly cycle cosine curve imitative parameters of the clinical features of liver cancer at different longitude and latitude].

OBJECTIVE: To explore whether there exists coincidence of the most appearing time of clinical features of liver cancer at different longitude and latitude, according to the law of field equation and the theory of warpage of space time by Einstein. METHODS: Three regions with different longitude and latitude were selected randomly and sampled. There were 36 items altogether, including 12 clinical items, which were used to imitate the yearly cycle cosine curve. The acorphases and the ratioes of amplitudes and means were compared to justifying whether they were in the same range. RESULTS: All the acorphases of 36 items appeared between -90.1degrees to -207.5 degrees (from april to july), existing in one third of the same range, in which 13 items occurred rhythmly (P<0.05). The image acorphases of liver cancer at the early and middle stage and gamma-glutamyl transpeptidase acorphase appeared between -98.5 degrees to -148.2 degrees (from april to may), in which 5 items occurred rhythmly (P<0.05). CONCLUSION: It is the same mode of the yearly biologcal cycle for liver cancer malignant growth within the most appearing time (from april to july). It will increase the detecting rate of liver cancer at the early and middle stage during this time (especially from april to may).

Strategies for chemoprevention of liver cancer.

Liver cancer is one of the most common cancers worldwide. Infection with hepatitis B virus and exposure to aflatoxins in the diet act synergistically to amplify risk. From a public health perspective, hepatitis virus vaccination programs and efforts to both reduce aflatoxin exposures and to attenuate the toxicological consequences of unavoidable exposures should have major impacts on the incidence of this disease. Experimentally, aflatoxin-induced hepatocarcinogenesis can be inhibited by over a score of different chemopreventive agents with multiple mechanisms of action. One agent, oltipraz, is a potent inducer of phase 2 enzymes involved in the detoxication of carcinogens including aflatoxin. A second agent, chlorophyllin, impedes the bioavailability of carcinogens by forming molecular complexes and enhances their elimination in the fecal stream. This review highlights the findings of recent randomized clinical trials with oltipraz and chlorophyllin conducted in individuals exposed to dietary aflatoxins and at high risk for development of liver cancer. Both chemopreventive agents modulated levels of aflatoxin biomarkers in the study participants in manners consonant with protection.