The impact of PTEN deletion and ERG rearrangement on recurrence after treatment for prostate cancer: a systematic review and meta-analysis.

BACKGROUND: The specific association between PTEN deletion or ERG rearrangement and the recurrence of prostate cancer (PC) treated with radical prostatectomy (RP) or brachytherapy is still unelaborated. Therefore, we performed a comprehensive meta­analysis to understand the impact of these factors on cancer recurrence. METHODS: A comprehensive literature search was performed in November 2018 based on PUBMED, EMBASE and Web of science database. Hazard ratio (HR) for biochemical recurrence free (BRF) which was defined as a PSA greater than or equal to 0.4 ng/mL after RP or another therapy for any detectable PSA and recurrence-free survival (RFS) which defined the time from the beginning of treatment to the earliest occurrence of local recurrence, distant metastasis or death. Which were extracted from eligible studies. I2 value was used to assess the pooled heterogeneity. RESULT: A total of 6744 patients from 17 studies were included in this analysis Overall, The pooled results showed that PTEN loss predict pooled BRF (HR 1.79, 95% CI 1.49-2.16, P < 0.001) and RFS (HR 1.71, 95% CI 1.50-1.95, P < 0.001) in patients after radical prostatectomy or brachytherapy for prostate cancer. Subgroup analysis revealed that PTEN deletion significantly predicted poor BRF or RFS in heterozygous studies group (HR 1.70, 95% CI 1.31-2.21, P < 0.001). The PTEN deletion also significantly predicted poor BRF or PFS in homozygous studies (HR 2.54, 95% CI 1.89-3.17, P < 0.001). And we had found that there was no significant association between ERG rearrangement and cancer recurrence regardless of PTEN loss or not. In addition, we concluded that Gleason score > 6 significantly predicted the poor BRF or RFS in studies, especially in Gleason score = 4 + 3 (HR 3.16, 95% CI 2.08-4.80, P < 0.01). CONCLUSION: This study presented that PTEN deletion significantly reduce time of BRF or RFS, especially based on homozygous deletion. And we also found ERG rearrangement in tumor cell could not significantly predict BRF or RFS.

The incidence proportion of erectile dysfunction in patients treated with cryotherapy for prostate cancer: a meta-analysis.

OBJECTIVES: With the maturity of cryotherapy for prostate cancer, the complications after operation are also decreasing, which can improve the prognosis of patients. However, erectile dysfunction (ED) is still one of the main complications after cryotherapy. Therefore, we performed a meta-analysis to evaluate the incidence of erectile dysfunction in patients after cryotherapy. MATERIALS AND METHODS: A comprehensive literature search was performed in August 2018. PUBMED and EMBASE databases were searched to collect studies reporting the incidence rate of ED after cryotherapy from 2002 to 2018. Two reviewers independently screened the literatures, extracted data and assessed the risk of bias of included studies. Pooled ratio and its 95% confidence intervals (95% CIs) were performed by Stata 12.1. RESULTS: Of the 157 articles identified on August 1st 2018, 23 studies which reported ED after cold ablative therapy were identified, however, only 12 used validated outcome measures and met inclusion criteria. A total of 12 studies were included in this meta-analysis. Overall, the results of this meta-analysis showed that the pooled incidence rate of ED was 0.27 (95% CI 0.26-0.28) which means that the incidence rate of ED after cryotherapy for prostate cancer was not high, but we still found that there are great heterogeneity between the 12 articles. By subgroup analysis, we found a statistically significant incidence rate of ED in primarily localized PCa which was 0.49 (95% CI 0.30-0.68), which is clearly lower than the incidence of recurrent prostate cancer after failed primary radiotherapy 0.61 (95% CI 0.43-0.79). CONCLUSION: ED is one of the major complications after cryotherapy for PCa. Furthermore, subgroup analysis revealed a higher incidence rate in PCa undergoing radiotherapy. Significantly, with the development of cryotherapy technology, the incidence of ED after cryotherapy for prostate cancer is decreasing. While we still need further researches to advance knowledge in this field.

CalliSpheres® drug-eluting beads (DEB) transarterial chemoembolization (TACE) is equally efficient and safe in liver cancer patients with different times of previous conventional TACE treatments: a result from CTILC study.

PURPOSE: To assess the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) in liver cancer patients with different times of previous conventional transarterial chemoembolization (cTACE) treatments. METHODS: 367 liver cancer patients about to receive DEB-TACE treatment were enrolled in this prospective cohort study. All patients were divided into no previous cTACE group (NPC group), 1-2 times previous cTACE group (PC group) and triple or above previous cTACE group (TPC group) according to the times of previous cTACE treatments. RESULTS: There was no difference in complete response (CR) (P = 0.671) and objective response rate (ORR) (P = 0.062) among three groups. Additionally, no difference in overall survival (OS) among groups (P = 0.899) was found. As to liver function, most liver function indexes were deteriorative at 1 week after DEB-TACE operation, but returned to baseline at 1-3 months after DEB-TACE operation in all three groups, while percentage of abnormal total bile acid (TBA) patients was higher in TPC group than NPC and PC groups at 1-3 month post-DEB-TACE (P = 0.018). As for safety profiles, the incidence of pain during DEB-TACE operation was lower in TPC group compared to NPC and PC groups (P = 0.005), while no difference of other adverse events was found during and 1 month post-DEB-TACE treatment among three groups. CONCLUSION: DEB-TACE treatment was equally efficient and tolerated in liver cancer patients with different times of previous cTACE treatments.

MiR-214 regulates oral cancer KB cell apoptosis through targeting RASSF5.

Ras association domain family member 5 (RASSF5), a member of the Ras association domain family, induces cell apoptosis by phosphorylating FOXO3a, which triggers target gene BIM (pro-apoptotic factor) activation. MiR-214 is overexpressed in oral cancer tissue, indicating its possible involvement in oral cancer pathogenesis. Bioinformatics analysis has revealed a complimentary sequence between miR-214 and the 3'-UTR of RASSF5 mRNA. However, whether miR-124 regulates RASSF5 in oral cancer remains poorly understood. We aimed to investigate the role of miR-214 in RASSF5 expression regulation in oral cancer. Tumor and paracarcinoma tissues were obtained from 48 oral cancer patients to examine miR-214 and RASSF5 expression. The relationship between miR-214 and RASSF5 was investigated by dual luciferase reporter gene assay. Oral cancer KB cells were cultured in vitro and divided into inhibitor NC, miR-214 inhibitor, Scramble-pMD18, RASSF5-pMD18, and miR-214 inhibitor + RASSF5-pMD18 groups. Caspase 3 activity, cell apoptosis, and total protein expression were measured by spectrophotometry, flow cytometry, and western blot, respectively. MiR-214 expression was significantly increased, while that of RASSF5 decreased in oral cancer tumor tissues compared to paracarcinoma tissues. Luciferase assay showed that miR-214 suppressed RASSF5 expression by targeting its 3'-UTR. Down-regulation of miR-214 and/or enhancement of RASSF5 expression markedly increased FOXO3a phosphorylation, BIM expression, caspase 3 activity, and apoptosis. In conclusion, miR-214 expression was elevated and RASSF5 was down-regulated in oral cancer. Moreover, miR-214 regulated KB cell apoptosis through targeted inhibition of RASSF5 expression, FOXO3a phosphorylation, and BIM expression, suggesting its possible application as a novel therapeutic oral cancer target.

Serum total bilirubin levels are negatively correlated with metabolic syndrome in aged Chinese women: a community-based study.

We evaluated serum total bilirubin levels as a predictor for metabolic syndrome (MetS) and investigated the relationship between serum total bilirubin levels and MetS prevalence. This cross-sectional study included 1728 participants over 65 years of age from Eastern China. Anthropometric data, lifestyle information, and previous medical history were collected. We then measured serum levels of fasting blood-glucose, total cholesterol, triglycerides, and total bilirubin, as well as alanine aminotransferase activity. The prevalence of MetS and each of its individual component were calculated per quartile of total bilirubin level. Logistic regression was used to assess the correlation between serum total bilirubin levels and MetS. Total bilirubin level in the women who did not have MetS was significantly higher than in those who had MetS (P<0.001). Serum total bilirubin quartiles were linearly and negatively correlated with MetS prevalence and hypertriglyceridemia (HTG) in females (P<0.005). Logistic regression showed that serum total bilirubin was an independent predictor of MetS for females (OR: 0.910, 95%CI: 0.863-0.960; P=0.001). The present study suggests that physiological levels of serum total bilirubin might be an independent risk factor for aged Chinese women, and the prevalence of MetS and HTG are negatively correlated to serum total bilirubin levels.

Growth Patterns of Two Chinese Native Goose Breeds

To study the development rules of Chinese native geese, two breeds, Shitou and Sichuan White geese were analyzed from 0 to 12 weeks of age. The growth curves were fitted with commonly used four kinds of nonlinear models (Logistic, Gompertz, Von Bertalanffy and Richards). The results showed that the growth curves were appropriately fitted with all four models but the Logistic and Richards both had the best fitting with growth curve (R2>0.99). Analyzing the fitting parameters of the Logistic and Richards, we found that male Shitou had the highest adult body weight while Sichuan White female had the lowest weight. In Shitou breed, Shape parameter Predicted with Richards model was corresponded with Gompertz curve, while in Sichuan breed it was in between Gompertz and Bertalanffy. Growth parameters predicted with Logistic model was much more closed to observed value as compared others. So overall logistic was the best model to analyze the growth curve in Chinese native goose and Shitou goose had excellent growth performance when compared to Sichuan White.

Growth Patterns of Two Chinese Native Goose Breeds

To study the development rules of Chinese native geese, two breeds, Shitou and Sichuan White geese were analyzed from 0 to 12 weeks of age. The growth curves were fitted with commonly used four kinds of nonlinear models (Logistic, Gompertz, Von Bertalanffy and Richards). The results showed that the growth curves were appropriately fitted with all four models but the Logistic and Richards both had the best fitting with growth curve (R2>0.99). Analyzing the fitting parameters of the Logistic and Richards, we found that male Shitou had the highest adult body weight while Sichuan White female had the lowest weight. In Shitou breed, Shape parameter Predicted with Richards model was corresponded with Gompertz curve, while in Sichuan breed it was in between Gompertz and Bertalanffy. Growth parameters predicted with Logistic model was much more closed to observed value as compared others. So overall logistic was the best model to analyze the growth curve in Chinese native goose and Shitou goose had excellent growth performance when compared to Sichuan White.(AU)

Association analysis of IGF-I gene expression with growth and reproductive traits in Jinghai yellow chickens.

The insulin-like growth factor, IGF-I, plays an important role in the development of growth and reproductive traits. Single-strand conformation polymorphism analysis was used to detect and analyze polymorphisms and expression profiles of the IGF-I gene and its association with growth and reproductive traits of Jinghai yellow chickens. A point mutation g.295T>C was detected in the IGF-I gene with three genotypes CC, CT, and TT. The CT and TT genotypes were found to be significantly (P < 0.05) superior to the CC genotype in 8-, 10-, 12-, 14-, and 16-week-age weight of chickens (for growth traits) and in body weight at first egg-laying (for reproductive traits). Comparison of the expression level between males and females showed similarity in their expression curves, with females showing relatively higher IGF-I expression than males in all studied tissues. A similar IGF-I expression pattern was observed in the breast and leg muscles of both males and females, with the leg muscle showing relative higher IGF-I expression than the breast muscle. Our results indicate that, g.295T>C mutation in the IGF-I gene affects certain growth and reproductive traits, and it could be used to provide a theoretical basis as well as marker-assisted selection to upgrade the development of Jinghai yellow chickens in future.

Detection of QTLs controlling fast kernel dehydration in maize (Zea mays L.).

In order to understand the effect of grain moisture of inbred lines at the silking and physiological maturity stages on kernel dehydration rate, 59 maize inbred lines from six subgroups were selected. Grain moisture was measured and QTLs associated with kernel dehydration were mapped. A rapid dehydration evaluation and association analysis revealed eight inbred lines with faster dehydration rate, including Yuanwu 02, K36, Zhonger/O2, Lo1125, Han 49, Qi 319, Hua 160, and PH4CV. A single sequence repeat analysis using 85 pairs detected five QTLs with phenotypic variation contribution ≥10% in the permanent F2 generation populations Zheng 58 x S1776 and Chang 7-2 x K1131, which had LOD threshold values ≥ 3 in both 2013 and 2014. The chromosome region of qFkdr7b had not previously been reported and is preliminarily identified as a new major QTL. A false positive field verification of grain dehydration rate of 53 inbred lines indicated that the screening result of the rapid dehydration inbred lines by specific amplification with marker Phi114 was most similar to the field assessment result, followed by markers Phi127 and Phi029. The rapid dehydration lines selected based on primer Phi114 amplification were also similar to the field dehydration rate and can thus be used for molecular marker-assisted selection. A significant effort is needed to improve stress resistance and shorten the growth period via fast kernel dehydration in intermediate materials of the inbred lines K36, Zhonger/ O2, Lo1125, Han 49, Hua 160, and PH4CV, and further using the selected lines for new combinations.

Short Communication Development of microsatellite markers and genetic diversity analysis for Pelodiscus sinensis.

Pelodiscus sinensis is a common freshwater soft-shell turtle found in China, and is an important aquaculture species. In this study, 20 polymorphic microsatellite primers were developed from the transcriptome. The genetic diversity of three populations of P. sinensis was evaluated, using 72 individuals. The number of alleles per locus ranged from 3 to 26. The observed and expected heterozygosities varied from 0.208 to 0.958, and from 0.302 to 0.963, respectively. The polymorphic information content varied from 0.283 to 0.953. No significant linkage disequilibrium was detected. These markers will be useful for future population genetic studies and molecular breeding of P. sinensis.

Rapid and sensitive LC-MS/MS method for the determination of auraptene in rat plasma and its application in a pharmacokinetic and bioavailability study in rats.

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of auraptene, a constituent isolated from Fructus aurantii with potential to combat Alzheimer's disease, in rat plasma. Rat plasma samples were pretreated by protein precipitation with methanol. The analytes were separated by a Waters Sun Fire C18 column (50 mm x 2 mm, 5 µm) and eluted with 1:1000 methanol and formic acid/water (v/v) mobile phase with a flow rate of 0.5 mL/min. Multiple reaction monitoring was used to monitor the transition of the deprotonated auraptene molecule with an m/z of 299.3 [M+H](+), to the product ion with an m/z of 162.9 [M+H](+). Progesterone, with an m/z of 315.2→ 96.9 was used as an internal standard. The limits of detection and of quantification of auraptene in the rat plasma were 1 and 5 ng/mL, respectively. The method was linear in the concentration range of 20- 2000 ng/mL with coefficient correlation of 0.9956. After auraptene (100 mg/kg, p.o.) administration, the maximum plasma concentration and the time taken to reach maximum concentration were 1719.5 ± 384.3 g/mL and 108.0 ± 25.3 min, respectively. The elimination half-life was 108.0 ± 25.3 for auraptene (100 mg/kg, p.o.) and 3.0 ± 0 min for auraptene (2 mg/kg, i.v.). The oral bioavailability was about 8.5%.

Serum levels of PSA, ALP, ICTP, and BSP in prostate cancer patients and the significance of ROC curve in the diagnosis of prostate cancer bone metastases.

Bone metastasis is a common complication in prostate cancer patients that can cause bone pain and pathological fracture. This study tested serum levels of prostate specific antigen (PSA), alkaline phosphatase (ALP), bone sialoprotein (BSP), collagen type I pyridine crosslinking peptide (ICTP) in prostate cancer patients and the significance of the receiver operator characteristic (ROC) curve in the diagnosis of prostate cancer bone metastases. Eighty-three prostate cancer patients were enrolled including 42 in the bone metastases group and 41 in the non-bone metastases group. Serum levels of BSP, ALP, ICTP, and PSA were highest in the bone metastases group followed by the non-bone metastases group, hyperplasia group, and then the control group (P < 0.05). Based on Gleason score, serum levels were highest in the poorly differentiated group followed by moderately differentiated and well-differentiated groups (P < 0.05). ROC curve analysis revealed that the diagnostic efficiency of the biomarkers in turn was BSP, PSA, ICTP, and ALP. The sensitivity of BSP, ALP, ICTP, and PSA in the diagnosis of prostate cancer bone metastases were 80.95, 57.14, 69.05, 71.43%, respectively, and the specificity of the same markers were 72.80, 64.80, 76.80, and 88.80%, respectively. Combined detection of the four markers improved sensitivity to 97.62% and the negative-predictive value increased to 97.60%. PSA + BSP showed the best efficiency when combining two markers. In conclusion, serum levels of BSP, ALP, ICTP, and PSA increased in patients with bone metastases, and combined detection of all markers could improve the positive-predictive value.

Identification of altered pathways in Down syndrome-associated congenital heart defects using an individualized pathway aberrance score.

The aim of this study was to identify disrupted pathways related to Down syndrome (DS), and DS-associated congenital heart defects (DS-CHD). The gene expression profile and pathway data of 10 human DS patients and 5 control samples in E-GEOD-1789 were recruited and analyzed by the individualized pathway aberrance score (iPAS) method, consisting of the data processing, gene-level statistics, pathway-level statistics, and significant measurement steps. The pre-processing step identified 12,493 genes and 1022 pathways (4269 genes). The pathway significant analysis identified eight pathways (adjusted P value <0.1) that differed between the disease and control samples. The cross-presentation of particulate exogenous antigen (phagosomes) and methionine salvage pathways showed the most significant differences among these. The gene expression levels of key pathway genes, such as CYBB and ADI1, were higher in disease samples than in normal controls. Based on our results, we predicted that the cross-presentation of particulate exogenous antigens (phagosomes) and the methionine salvage pathway could be good indicators of DS-CHD.

Evaluation of the semen swim-up method for bovine sperm RNA extraction.

Isolation of high-quality RNA is important for assessing sperm gene expression, and semen purification methods may affect the integrity of the isolated RNA. This study evaluated the effectiveness of the sperm swim-up method for seminal RNA isolation. Frozen semen samples in straws from three bulls of proven fertility were purified by the swim-up method. RNA extraction was carried out using the E.Z.N.A.(TM) Total RNA kit II, with non-swim-up sperm as a control. Total sperm RNA was analyzed by UV spectrophotometry, reverse transcription polymerase chain reaction (RT-PCR), and agarose gel electrophoresis, and expression of the sex-determining region on the Y chromosome (SRY), leptin (LEP), and ribosomal protein subunit 23 (RPS23) genes, were determined. 18S RNA was used as a positive control. Fewer somatic cells were found in sperm swim-up samples than in the non-swim-up counterparts (0 x 10(3) vs 17.33 ± 2.52 x 10(3) sperm, P < 0.05). In addition, high-quality RNA was obtained in about 2 h, with no significant difference between groups. Interestingly, the yields of RNA fragments containing ≥200 nucleotides were significantly reduced in sperm swim-up samples (0.92 ± 0.41 x 10(7) sperm) compared with the non-swim-up samples (1.36 ± 0.33 x 10(7) sperm, P < 0.05). After RT-PCR, clear bands representing SRY, LEP, and RPS23 in sperm cDNA were observed on agarose gel electrophoresis. Finally, no bands corresponding to 18S RNA were found in RNA samples from the sperm swim-up group. Our findings suggest that small amounts of sperm RNA can be efficiently extracted from frozen straw semen samples using the swim-up technique.

Isolation and characterization of the Chrysanthemum nitrate transporter CmNRT1.

In this study, the nitrate transporter gene CmNRT1 was isolated from the chrysanthemum variety 'Nannongxuefeng'. The full-length cDNA contains an open reading frame of 1761 bp encoding 587 residues. Using qRT-PCR, we found that CmNRT1 was induced by 10 mM NO3(-) in roots and shoots. Two Arabidopsis thaliana transgenic plants expressing CmNRT1 were selected for functional analyses. Root (15)N influx in wild-type and transgenic A. thaliana lines under 10 or 0.2 mM (15)NO3 was tested. Our results indicate that CmNRT1 encodes a constitutive component for a low-affinity transporter.

Genome-wide identification and evolutionary analysis of nucleotide-binding site-encoding resistance genes in Lotus japonicus (Fabaceae).

Nucleotide-binding site (NBS) disease resistance genes play a crucial role in plant defense responses against pathogens and insect pests. Many NBS-encoding genes have been detected in Lotus japonicus, an important forage crop in many parts of the world. However, most NBS genes identified so far in L. japonicus were only partial sequences. We identified 45 full-length NBS-encoding genes in the L. japonicus genome, and analyzed gene duplications, motifs, and the molecular phylogeny to further understand the NBS gene family. We found that gene duplication events rarely occur in L. japonicus NBS-encoding (LjNBS) genes. In addition, LjNBS genes were subjected to selection pressure, and codon usage bias was evident. We tested for purifying selection (specifically in the CC-NBS-LRR and TIR-NBS-LRR groups), and found strong purifying selection in the TIR-domain-containing sequences, indicating that the CC-NBS-LRR group is more likely to undergo expansion than the TIR-NBS-LRR group. Moreover, our results showed that both selection and mutation contributed to LjNBS codon usage bias, but mutational bias was the major influence on codon usage.

Cytotoxicity of 1-dodecyl-3-methylimidazolium bromide on HepG2 cells.

We evaluated the cytotoxicity of 1-dodecyl-3-methylimidazo-lium bromide ([C12mim][Br]) on HepG2 cells and its influence on plasma membrane permeability. The results showed that [C12mim][Br] inhibited HepG2 cell growth and decreased cell viability in a concentration-depen-dent manner. The results also revealed that [C12mim][Br] exposure induced apoptosis in [C12mim][Br]-treated HepG2 cells. In addition, the results showed that [C12mim][Br] increased membrane permeability in HepG2 cells. These results suggest that plasma membrane permeability may be responsible for apoptosis induced by [C12mim][Br] in HepG2 cells.

PPARα signal pathway gene expression is associated with fatty acid content in yak and cattle longissimus dorsi muscle.

Intramuscular fatty acid (FA) is related to meat qualities such as juiciness, tenderness, palatability, and shear force. PPARα plays an important role in lipid metabolism in the liver and skeletal muscle. This study investigated FA composition in yaks and cattle, in order to ascertain whether a correlation between PPARα signal pathway genes as candidate genes and meat FA composition in yaks and cattle exists. Statistical analyses revealed that levels of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) in yaks were significantly higher than those in cattle (P < 0.01), whereas saturated fatty acid (SFA) levels were significantly lower than those in cattle (P < 0.05). The mRNA expression levels of FABP4 (P < 0.05), SCP2 (P < 0.05), and APOA1 (P < 0.01) in yaks were significantly lower than those in cattle. However, LPL expression in yaks was significantly higher than that in cattle (P < 0.05). In yaks, the expression levels of FABP3 (P < 0.05) and LPL (P < 0.01) were negatively correlated with MUFA, and those of FABP4 and SCD were positively correlated with PUFA (P < 0.01). In cattle, the mRNA level of PLTP was positively correlated with SFA (P < 0.05), and LPL was positively correlated with MUFA (P < 0.05). These results suggest that these genes may participate in the regulation and control of intramuscular FA metabolism in yaks, so they could be used as candidate markers to improve yak meat quality.

New compound heterozygous mutations of p. Thr101Ilefs 2 and p. Thr306Ale in a child from a Chinese family with 17α-hydroxylase/17, 20-lyase deficiency.

We determined whether a child with 17α-hydroxylase/17, 20-lyase deficiency possessed the sex-determining region (SRY) gene, and examined the mutations present in the CYP17A1 gene that led to 17α-hydroxylase/17, 20-lyase deficiency. In the child, karyotype analysis was performed and polymerase chain reaction analysis and electrophoretic techniques were used to identify the SRY gene. A total of 50 normal individuals were included as a control group. Polymerase chain reaction and DNA sequencing were used to identify CYP17A1 gene mutations in all samples. The karyotype of the child was 46, XY, which was inconsistent with her social sex, SRY was positive, and a compound heterozygous mutation p. Thr101Ilefs*2 in exon 2 and p. Thr306Ale in exon 5 were identified in the CYP17A1 gene. These mutations were inherited from her parents. In the 20 normal individuals, these mutations were not identified. In the child, sex reversal may have been caused by CYP17A1 mutations. The compound heterozygous mutation of p. Thr101Ilefs*2 and p. Thr306Ale is a new gene mutation of 17α-hydroxylase/17, 20-lyase deficiency.