Aberrant miRNA expression has been reported in endometriosis and miRNA gene polymorphisms have been linked to cancer. Because certain ovarian cancers arise from endometriosis, we genotyped seven ...cancer-related miRNA single nucleotide polymorphisms (MiRSNPs) to investigate their possible roles in endometriosis. Genetic variants in MIR196A2 (rs11614913) and MIR100 (rs1834306) were found to be associated with endometriosis development and related clinical phenotypes, such as infertility and pain. Downstream analysis of the MIR196A2 risk allele revealed upregulation of rRNA editing and protein synthesis genes, suggesting hyper-activation of ribosome biogenesis as a driving force for endometriosis progression. Clinical studies confirmed higher levels of small nucleolar RNAs and ribosomal proteins in atypical endometriosis lesions, and this was more pronounced in the associated ovarian clear cell carcinomas. Treating ovarian clear cells with CX5461, an RNA polymerase I inhibitor, suppressed cell growth and mobility followed by cell cycle arrest at G2/M stage and apoptosis. Our study thus uncovered a novel tumorigenesis pathway triggered by the cancer-related MIR196A2 risk allele during endometriosis development and progression. We suggest that anti-RNA polymerase I therapy may be efficacious for treating endometriosis and associated malignancies.
BACKGROUND: A lipid emulsion composed of soybean oil (long-chain triglycerides, LCT), medium-chain triglycerides (MCT) and n-3 poly-unsaturated fatty acids (PUFAs) was evaluated for immune-modulation ...efficacy, safety, and tolerance in patients undergoing major surgery for gastric and colorectal cancer. METHODS: In a prospective, randomized, double-blind study, 99 patients with gastric and colorectal cancer receiving elective surgery were recruited and randomly assigned to either the study group, receiving the n-3 PUFAs enriched intravenous fat emulsion (IVFE), or the control group, receiving a lipid emulsion comprised of soybean oil and MCTs (0.8 – 1.5 g · kg⁻¹ · day⁻¹) as part of total parenteral nutrition (TPN) regimen from surgery (day -1) up to post-operative day 7. Safety and efficacy parameters were assessed on day -1 and post-operative visits on day 1, 3, and 7. Adverse events were documented daily and compared between the groups. RESULTS: Pro-inflammatory markers, laboratory parameters, and adverse events did not differ prominently between the 2 groups, with the exception of net changes (day 7 minus day -1) of free fatty acids (FFAs), triglyceride, and high-density lipoprotein (HDL). Net decrease of FFAs was remarkably higher in the study group, while the net increase of triglyceride and decrease of HDL was significantly lower. CONCLUSIONS: The n-3 PUFA-enriched IVFE showed improvements in lipid metabolism. In respect of efficacy, safety and tolerance both IVFE were comparable. In patients with severe stress, there is an inflammation-attenuating effect of n-3 PUFAs. Further, adequately powered clinical trials will be necessary to address this question in postsurgical GI cancer patients. TRIAL REGISTRATION: US ClinicalTrials.gov NCT00798447 .
Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP.
We conducted genome-wide analysis among 18 422 East ...Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a
<5.0×10
and 2.5×10
, respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel
variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1
=5.03×10
, stage-2
=8.64×10
, joint
=2.63×10
) and mean arterial pressure (stage-1
=3.59×10
, stage-2
=2.35×10
, joint
=2.64×10
). Three previously reported BP loci (
,
, and
) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of
with LTA systolic BP (stage-1
=8.55×10
, stage-2
=1.62×10
, joint
=3.28×10
) and mean arterial pressure (stage-1
=9.19×10
, stage-2
=9.69×10
, joint
=2.15×10
) phenotypes. Fourteen genes (
,
,
,
,
,
,
,
,
-
,
,
, and
at 10q24.32;
at 12q21.33; and
at 11p15.1) implicated by previous genome-wide association study meta-analyses were also identified. Among the loci identified by the previous genome-wide association study meta-analysis of LTA BP, we transethnically replicated associations of the
marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes (
=1.27×10
and 3.30×10
, respectively).
We identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the
locus for LTA BP among East Asians.
To investigate the 2-year outcomes of the natural history of retinopathy of prematurity (ROP) in Taiwan.
A prospective study was conducted at two tertiary medical centers. Premature infants were ...screened and examined for ROP. The postmenstrual ages of developing each stage of ROP and the associated risk factors were recorded.
A total of 698 infants were included. The incidences of ROP and treatment-requiring ROP in all patients with ROP were 29.7% and 37.2%. When only including patients with birth weight of 1,250 g or less, the incidences were 62.2% and 39.1%, respectively. In patients with ROP with birth weight over 1,250 g, 25% of them developed treatment-requiring ROP. The median postmenstrual ages for the development of Stage 1, Stage 2, and Type 1 ROP were 33.0, 34.0, and 34.7 weeks, respectively. Gestational age at birth and birth weight were the most important factors associated with treatment-requiring ROP (hazard ratios of 0.3 and 0.6).
Our hospital-based study reveals an earlier postmenstrual age of developing ROP in this Asian population than in the Early Treatment for ROP study. Infants with birth weight over 1,250 g could still develop treatment-requiring ROP. Suboptimal oxygen control, different genetic dispositions among different races, inconsistencies in ROP diagnosis, and earlier screening might account for such a phenomenon.
Background. The prevalence of sexual dysfunction among male haemodialysis patients is high. Sexual dysfunction is composed of both physiological and psychological factors. However, the role of ...pyschological depression is still obscure. Methods. A multicentre cross-sectional study of 411 male haemodialysis patients was conducted to define the determinants of sexual dysfunction. Mid-week pre-dialytic biochemical and haematological parameters were obtained. All patients were required to complete three questionnaires by themselves: (i) the International Index of Erectile Function (IIEF, Chinese version); (ii) the Beck Depression Inventory (BDI, Chinese version) and (iii) the 36-item Short Form Health Survey Questionnaire (SF-36, Taiwan Standard Version 1.0). Results. In total, 154 male patients completed the IIEF questionnaire. Their mean age was 50.2 ± 10.7 years. A linear multivariable regression analysis demonstrated advanced age, diabetes and the presence of depressive symptoms to be independently associated with sexual dysfunction. Subjects with sexual dysfunction had significantly lower quality of life scores. Conclusions. The presence of depressive symptoms, highly prevalent in haemodialysis patients, is an independent factor of sexual dysfunction in male haemodialysis patients. In a comprehensive approach to the management of sexual dysfunction, a thorough evaluation of psychological depression must be included.
Abstract Background Sex and sodium/calcium regulation play critical roles in cardiac electrophysiology and atrial arrhythmogenesis. We investigated whether sodium and calcium contributed to sex ...differences in atrial electrophysiology. Methods Whole-cell patch clamp techniques and the indo-1 fluorometric ratio technique were used to investigate the ionic current and intracellular calcium in single isolated male and female rabbit myocytes from the left atrium posterior wall (LAPW) and right atrium (RA). Results Female LAPW ( n = 95) and RA ( n = 49) myocytes had larger cell widths (15.1 ± 0.4 vs. 13.8 ± 0.4 μm, p < 0.05; 14.9 ± 0.6 vs. 13.5 ± 0.4 μm, p < 0.05) than male LAPW ( n = 142) and RA ( n = 57) myocytes. Male LAPW myocytes ( n = 26) had a higher incidence (57 vs. 16%, p < 0.05) of delayed afterdepolarizations (DADs) than female LAPW myocytes ( n = 24) but there were similar incidences (20 vs. 20%, p > 0.05) of DADs in male and female RA myocytes. The late sodium current, calcium transients, and sarcoplasmic reticulum calcium contents were larger in male than female LAPW myocytes but were similar in male and female RA myocytes. However, the ICa-L and nickel-sensitive sodium/calcium exchanger currents were similar between two groups. Different from those in female myocytes, ouabain (10 μM) only induced repeated atrial beats (0 to 45%, p < 0.05) in male myocytes ( n = 11). Moreover, ranolazine (3 μM) perfusion (4.5 ± 0.6 vs. 1 min, p < 0.05) was required to decrease the amplitude of DADs in male but not female LAPW myocytes. Conclusions Increased late sodium currents and calcium contents may contribute to higher arrhythmogenesis in male LAPW myocytes.
With the recent development of molecular markers, strategies for identifying patients with colorectal cancer (CRC) having a high risk of postoperative early relapse (within 1 y) and relapse have been ...improved. We previously constructed a multigene biochip with 19 candidate genes. The objective of the present study was to optimize a multigene biochip for detecting the risk of postoperative early relapse and relapse in patients with CRC.
We included 357 patients with stage I-III CRC who underwent curative resection at a single institution between June 2010 and May 2015. During each follow-up, a postoperative surveillance strategy including the National Comprehensive Cancer Network recommendations and a multigene biochip was used. A statistical algorithm was developed to select candidate biomarkers for an optimal combination.
After a 30.9-mo median follow-up, 67 patients (18.8%) had postoperative relapse, of whom 25 (7.0%) relapsed within 1 y after operation and accounted for 37.3% of all relapsed patients. Of the 19 circulating biomarkers, ELAVL4, PTTG1, BIRC5, PDE6D, CHRNB1, MMP13, and PSG2, which presented significant predictive validity, were selected for combination. The expression of the seven-biomarker biochip resulted in area under the receiver operating characteristic curve values of 0.854 (95% confidence interval: 0.756-0.952) for early relapse and 0.884 (95% confidence interval: 0.830-0.939) for relapse. Moreover, the sensitivity, specificity, and predictive accuracy levels were 84.0%, 83.1%, and 83.2% for early relapse and 76.1%, 91.0%, and 88.2% for relapse (P = 0.415, 0.006, and 0.054, respectively). The median lead times before the detection of postoperative early relapse and relapse were 3.8 and 10.4 mo, respectively.
From 19 circulating biomarkers, we optimized seven contemporary circulating biomarkers. The prediction model used for the early and accurate identification of Taiwanese patients with CRC having a high risk of postoperative early relapse and relapse seems to be feasible and comparable.
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