[Show abstract][Hide abstract] ABSTRACT: Next-generation sequencing technology has provided a great opportunity for inferring human demographic history by investigating changes in the effective population size (Ne). In this report, we introduce a strategy for estimating Ne dynamics, allowing the exploration of large multi-locus SNP datasets. We applied this strategy to the Phase 1 Han Chinese samples from the 1000 Genomes Project. The Han Chinese population has undergone a continuous expansion since 25,000 years ago, at first slowly from about 7,300 to 9,800 (at the end of the last glacial maximum about 15,000 YBP), then more quickly to about 46,000 (at the beginning of the Neolithic about 8,000 YBP), and then even more quickly to reach a population size of about 140,000 (recently).
[Show abstract][Hide abstract] ABSTRACT: Two-thirds of patients in the United States with newly diagnosed lung cancer would not meet the current U.S. Preventive Services Task Force (USPSTF) screening criteria, which suggests a need for amendment of the definition of high risk. To provide evidence of additional high-risk subpopulations and estimated gains and losses from using different criteria for screening eligibility, we conducted a two-step study using three cohorts.
[Show abstract][Hide abstract] ABSTRACT: Inflammation drives asthma and atherosclerosis. Clinical studies suggest that asthmatic patients have a high risk of atherosclerosis. Yet this hypothesis remains uncertain, given that Th2 imbalance causes asthma whereas Th1 immunity promotes atherosclerosis. In this study, chronic allergic lung inflammation (ALI) was induced in mice by ovalbumin sensitization and challenge. Acute ALI was induced in mice by ovalbumin and aluminum sensitization and ovalbumin challenge. Atherosclerosis was produced in apolipoprotein E-deficient (Apoe–/–) mice with a Western diet. When chronic ALI and atherosclerosis were produced simultaneously, ALI increased atherosclerotic lesion size, lesion inflammatory cell content, elastin fragmentation, smooth muscle cell (SMC) loss, lesion cell proliferation, and apoptosis. Production of acute ALI before atherogenesis did not affect lesion size, but increased atherosclerotic lesion CD4+ T cells, lesion SMC loss, angiogenesis, and apoptosis. Production of acute ALI after atherogenesis also did not change atherosclerotic lesion area, but increased lesion elastin fragmentation, cell proliferation, and apoptosis. In mice with chronic ALI and diet-induced atherosclerosis, daily inhalation of a mast cell inhibitor or corticosteroid significantly reduced atherosclerotic lesion T-cell and mast cell contents, SMC loss, angiogenesis, and cell proliferation and apoptosis, although these drugs did not affect lesion area, compared with those that received vehicle treatment. In conclusion, both chronic and acute ALI promote atherogenesis or aortic lesion pathology, regardless whether ALI occurred before, after, or at the same time as atherogenesis. Anti-asthmatic medication can efficiently mitigate atherosclerotic lesion pathology.
[Show abstract][Hide abstract] ABSTRACT: Background:
K-trigger signals from light source or external Mach-Zehnder interferometer are commonly used in swept source optical coherence tomography (SS-OCT) to achieve interference signal sampling and resolution enhancement. But extra signal transmission time is required due to the increased complexity of interference system using k-trigger signals, resulting in a misalignment (a.k.a., time delay) between the k-trigger and the interference signals.
The objective of this paper is to propose a numerical technique to correct the time delay between these two signals.
The time delay is iterated in this technique and each iterated correction result is evaluated through calculating the full width at half maximum (FWHM) of peaks in time-domain. The precise alignment between the k-trigger and interference signals coincides with the minimum value of FWHM.
The experimental results show that the FWHM can be improved by up to 50% using this time delay correction technique.
The proposed technique assists to provide precise sample tomography, thus enhancing the way of understanding sample characteristic.
No preview · Article · Dec 2015 · Journal of X-Ray Science and Technology
[Show abstract][Hide abstract] ABSTRACT: Preclinical studies show that GABA exerts anti-diabetic effects in rodent models of type 1 diabetes. Because little is known about its absorption and effects in humans, we investigated the pharmacokinetics and pharmacodynamics of GABA in healthy volunteers. Twelve subjects were subjected to an open-labeled, three-period trial involving sequential oral administration of placebo, 2 g GABA once, and 2 g GABA three times/day for 7 days, with a 7-day washout between each period. GABA was rapidly absorbed (Tmax: 0.5 ~ 1 h) with the half-life (t1/2) of 5 h. No accumulation was observed after repeated oral GABA administration for 7 days. Remarkably, GABA significantly increased circulating insulin levels in the subjects under either fasting (1.6-fold, single dose; 2.0-fold, repeated dose; p < 0.01) or fed conditions (1.4-fold, single dose; 1.6-fold, repeated dose; p < 0.01). GABA also increased glucagon levels only under fasting conditions (1.3-fold, single dose, p < 0.05; 1.5-fold, repeated dose, p < 0.01). However, there were no significant differences in the insulin-to-glucagon ratio and no significant change in glucose levels in these healthy subjects during the study period. Importantly, GABA significantly decreased glycated albumin levels in the repeated dosing period. Subjects with repeated dosing showed an elevated incidence of minor adverse events in comparison to placebo or the single dosing period, most notably transient discomforts such as dizziness and sore throat. However, there were no serious adverse events observed throughout the study. Our data show that GABA is rapidly absorbed and tolerated in human beings; its endocrine effects, exemplified by increasing islet hormonal secretion, suggest potential therapeutic benefits for diabetes.
Full-text · Article · Nov 2015 · Frontiers in Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Objective:
Asthma and abdominal aortic aneurysms (AAA) both involve inflammation. Patients with asthma have an increased risk of developing AAA or experiencing aortic rupture. This study tests the development of one disease on the progression of the other.
Approach and results:
Ovalbumin sensitization and challenge in mice led to the development of allergic lung inflammation (ALI). Subcutaneous infusion of angiotensin II into mice produced AAA. Simultaneous production of ALI in AAA mice doubled abdominal aortic diameter and increased macrophage and mast cell content, arterial media smooth muscle cell loss, cell proliferation, and angiogenesis in AAA lesions. ALI also increased plasma IgE, reduced plasma interleukin-5, and increased bronchioalveolar total inflammatory cell and eosinophil accumulation. Intraperitoneal administration of an anti-IgE antibody suppressed AAA lesion formation and reduced lesion inflammation, plasma IgE, and bronchioalveolar inflammation. Pre-establishment of ALI also increased AAA lesion size, lesion accumulation of macrophages and mast cells, media smooth muscle cell loss, and plasma IgE, reduced plasma interleukin-5, interleukin-13, and transforming growth factor-β, and increased bronchioalveolar inflammation. Consequent production of ALI also doubled lesion size of pre-established AAA and increased lesion mast cell and T-cell accumulation, media smooth muscle cell loss, lesion cell proliferation and apoptosis, plasma IgE, and bronchioalveolar inflammation. In periaortic CaCl2 injury-induced AAA in mice, production of ALI also increased AAA formation, lesion inflammation, plasma IgE, and bronchioalveolar inflammatory cell accumulation.
This study suggests a pathological link between airway allergic disease and AAA. Production of one disease aggravates the progression of the other.
No preview · Article · Nov 2015 · Arteriosclerosis Thrombosis and Vascular Biology
[Show abstract][Hide abstract] ABSTRACT: Background:
In OCT system, the chromatic dispersion of sample decreases the resolution and increases the depth misplacement. The developed numerical dispersion compensation techniques usually do not consider the higher order dispersion and time-consuming.
We proposed a numerical compensation technique for correcting depth error and resolution deterioration in Fourier domain optical coherence tomography (FD-OCT).
Firstly, the rough depth of each scatter in multilayer sample is estimated through magnification curve. Then the depth of a scatter is iterated to minimum the residual of this scatter in the time domain. At last, the spectrum of the scatter is reconstructed and dispersion can be compensated with the tracked depth.
The results show that the depth error is corrected to less than resolution level and the resolution is corrected to nearly ideal.
The technique proposed can provide precise sample tomography, thus enhancing the understanding of sample character.
No preview · Article · Sep 2015 · Journal of X-Ray Science and Technology
[Show abstract][Hide abstract] ABSTRACT: Objective:
To investigate the efficacy of transcranial color Doppler ultrasound (TCCS) combined with microbubbles (MBs) and rt-PA (recombinant tissue plasminogen activator) for thrombolysis in vivo.
An arterial embolization model was established in Sprague-Dawley rats by retrograde placement of autologous thrombi into the common carotid artery followed by ligation of external carotid artery and temporary occlusion of the carotid artery and internal carotid artery by clamping. The animals were divided into 5 groups with 6 rats in each group: ① untreated control group, ② rt-PA group, ③ TCCS+MBs group, ④ TCCS+MBs+rt-PA group, ⑤ TCCS+MBs+1/2 rt-PA+group. Thrombolytic effects including recanalization rate and recanalization grade were evaluated with grayscale and color Doppler ultrasound post treatment. Examination of histological change in the involved vessel was performed at the end of the experiments.
Thrombolysis in terms of recanalization rate and recanalization grade was observed in the treated groups in a time-dependent manner, except the TCCS+MBs group. Addition of rt-PA remarkably enhanced the therapeutic lysis in TCCS+MBs group. However, no difference of therapeutic effects existed between TCCS+MBs+rt-PA group and TCCS+MBs+1/2 rt-PA group.
TCCS+MBs combined with rt-PA is a relatively effective approach for ischemic arterial thrombosis with an additive or synergistic effect.
No preview · Article · Sep 2015 · Thrombosis Research
[Show abstract][Hide abstract] ABSTRACT: This study aimed to investigate the validity and reliability of the Chinese parent version of the Autism Spectrum Rating Scale (ASRS, 6-18 years) for a general sample of Chinese children. The study involved assessing 1625 community-based subjects aged 6-12 years from four sites (Shanghai, Guangzhou, Changsha, and Harbin city) in China and 211 clinic-based participants aged 6-18 with a confirmed diagnosis of autism spectrum disorders (ASDs). The internal consistency (Cronbach's alpha) ranged from 0.585 to 0.929, and the test-retest reliability (interclass correlations) ranged from 0.542 to 0.749, indicating no significant difference between the two tests at an interval of 2-4 weeks. The construct validity was relatively excellent, and the concurrent validity with the Social Responsiveness Scale (SRS) (Pearson correlations) was 0.732 between the two total scores. Receiver operating characteristics (ROC) analyses showed excellent and comparable discriminant validity of the ASRS with respect to the SRS, with an area under the curve (AUC) of 0.9507 (95% CI: 0.93-0.97) versus 0.9703 (95% CI: 0.96-0.98), respectively. Our data suggested a cutoff ≥60 for the Chinese version of the ASRS, with good accuracy in screening autism symptoms (sensitivity=94.2%, specificity=77%). The Chinese parent version of the ASRS is therefore a reliable and valid tool for screening autistic symptoms in Chinese children in general.
[Show abstract][Hide abstract] ABSTRACT: Hypoxia inducible factors, including HIF1A and HIF2A, play central roles in response to high-altitude hypoxia and genetic variants of HIF1A or HIF2A were associated with high-altitude sickness or adaptation. However, it remains to determine whether they are associated with tolerance to different levels of high-altitude selection pressure among native Tibetans. We recruited 189 Tibetan subjects living at 2,700 meters (Low level of high altitude, LHA), 197 at 3,200 meters (Middle level of high altitude of high altitude, MHA), 249 at 3,700 meters (High level of high altitude, HHA) and 269 at 4,700 meters (Very high level of high altitude, VHA) and performed association analysis of twelve tSNPs (tagging SNPs) in HIF1A and HIF2A with high-altitude. We found (1) a increasing trend of HIF2A rs5621780-C(18.4%, 15.9%, 32.8% and 31.1%, respectively, in LHA, MHA, HHA and VHA)(P = 3.56E-9); (2) increasing trends of HIF2A rs6756667-A(68.7%, 73.4%, 79.9% and 89.6%), rs7589621- G(74.6%, 77.9%, 83.7%, and 92.1%) and rs1868092-A(64.1%, 67.3%, 75.1% and 84.4%) (P = 3.56E-9, 4.68E-16, 1.17E-13 and 7.09E-14, respectively); (3) a increasing trend of haplotype AG (68.7%, 73.1%, 79.9% and 89.6%) (P = 2.22E-7) which was constructed by rs6756667 and rs7589621; (4) a strong linear correlation between major alleles of rs6756667-A (R2 = 0.997, P = 0.002), rs7589621-G (R2 = 0.994, P = 0.003), rs1868092-A (R2 = 0.985, P = 0.008) and altitude by linear correlation test. The associations between HIF2A variants and different level of high altitude support that extremely high-altitude hypoxia challenge imposes selective effects on HIF2A variants among native Tibetans.
[Show abstract][Hide abstract] ABSTRACT: Author Summary
Phosphoglycerate kinase (PGK1) catalyzes the reversible phosphotransfer reaction from 1, 3-bisphosphoglycerate (1, 3-BPG) to ADP to form 3-phosphoglycerate (3-PG) and ATP. By controlling ATP and 3-PG levels, PGK1 plays an important role in coordinating energy production with biosynthesis and redox balance. In contrast to the extensive investigation of the transcriptional regulation of PGK1, little is known about its post-translational regulation. Here, we report that PGK1 is acetylated at lysine 220 (K220) and this acetylation inhibits PGK1 activity by disrupting the binding with its substrate, ADP. We have identified KAT9 and HDAC3 as the acetyltransferase and deacetylase, respectively, for PGK1. Moreover, we show there is molecular crosstalk between mTOR-mediated HDAC3 S424 phosphorylation and PGK1 K220 acetylation. Our study uncovers a previously unknown mechanism for the insulin and mTOR pathway in regulating glycolytic ATP production and cellular redox potential via HDAC3-mediated PGK1 deacetylation.
[Show abstract][Hide abstract] ABSTRACT: A strong association between smoking and SCLC is noted whereas the dose–response relationships are less clear. We demonstrate that cumulative smoking of the first 50 pack-years is associated with a sharper increase in SCLC risk. Moreover, although the relationship between smoking and COPD or COPD and SCLC is well-established, no study has investigated the causal pathway among smoking, COPD, and SCLC. Here we reveal the risks of smoking behaviors on SCLC which are partially mediated (up to 7.6%) through COPD. The findings warrant further experimental study to elucidate the mechanisms in this causal pathway.
[Show abstract][Hide abstract] ABSTRACT: Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus–pituitary–adrenal (HPA) axis function was completely recovered after pregnancy and delivery.
In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery.
The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus–pituitary–adrenal (HPA) axis function was completely recovered. The peak serum cotisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation.
Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary cooperation during the pregnancy of patients with hypopituitarism. This case indicates that the pituitary function may partially recover after pregnancy in panhypopituitarism patients.
[Show abstract][Hide abstract] ABSTRACT: Background:
It has been considered that the detection methods for circulating tumor cells (CTCs) based on epithelial cell adhesion molecule (EpCAM) underestimate the number of CTCs and may miss a metastatic subpopulation with cancer stem cell (CSC) properties. Therefore, we investigated EpCAM-positive and -negative CTCs in non-small cell lung cancer (NSCLC) patients at different stages, assessed the clinical value of these CTCs and explored their capacity in the following CSC model.
CTCs were enriched by the depletion of leukocytes with bi-antibodies using a magnetic bead separation technique and then identified by the expression of EpCAM and cytokeratin 7 and 8 using multi-parameter flow cytometry. We determined the distribution of CTCs classified by the expression of EpCAM in 46 NSCLC patients with stages I to IV, assessed the diagnostic value of these CTCs by longitudinal monitoring in 4 index patients during adjuvant therapy and characterized the stemness of these CTCs by the expression of CXCR4 and CD133 in 10 patients.
EpCAM-negative (E-) CTCs were detected to be significantly higher than EpCAM-positive (E+) CTCs in stage IV (p = 0.003). The patients with the percentage of E-CTCs more than 95% (r > 95%) were detected to be significantly increased from 13.3% in stage I-II to 61.1% in stage IV (p = 0.006). Kaplan-Meier analysis indicated that the patients with r > 95% had significantly shorter survival time than those with r ≤ 0.95 (p = 0.041). Longitudinal monitoring of CTCs indicated that the patients with a high percentage of E-CTCs in the blood were not responsive to either chemotherapy or targeted therapy. Further characterization of CTCs revealed that a stem-like subpopulation of CXCR4+CD133+ CTCs were detected to be significantly more prevalent in E-CTCs than that in E+CTCs (p = 0.005).
The enrichment of CTCs by the depletion of leukocytes with bi-antibodies is a valuable method for estimating the number of CTCs, which can be potentially applied in predicting the prognosis, monitoring the therapeutic effect of NSCLC patients and further analyzing the biology of CTCs.
[Show abstract][Hide abstract] ABSTRACT: Testing dependence/correlation of two variables is one of the fundamental tasks in statistics. In this work, we proposed a new way of testing nonlinear dependence between two continuous variables (X and Y).
We addressed this research question by using CANOVA (continuous analysis of variance, software available at https://sourceforge.net/projects/canova/ ). In the CANOVA framework, we first defined a neighborhood for each data point related to its X value, and then calculated the variance of the Y value within the neighborhood. Finally, we performed permutations to evaluate the significance of the observed values within the neighborhood variance. To evaluate the strength of CANOVA compared to six other methods, we performed extensive simulations to explore the relationship between methods and compared the false positive rates and statistical power using both simulated and real datasets (kidney cancer RNA-seq dataset).
We concluded that CANOVA is an efficient method for testing nonlinear correlation with several advantages in real data applications.
Full-text · Article · Aug 2015 · BMC Bioinformatics
[Show abstract][Hide abstract] ABSTRACT: Objectives:
The purpose was to evaluate whether BI-RADS (the Breast Imaging Recording and Data System) combined with UE (ultrasound elastography) could improve the differentiation and characterization of benign and malignant breast lesions by comparing with BI-RADS.
A total of 1080 patients with 1194 breast lesions were studied retrospectively at 8 different institutions from 3 geographic areas across China (North, South, and West) from June 2010 to March 2012. Each institutional ethic review board approved the study and all patients gave written informed consent. All the cases were examined by conventional US (ultrasonography) and UE prior to ultrasound-guided core biopsy. Performance of BI-RADS and BI-RADS combined with UE were compared in different size groups, age groups and area groups.
BI-RADS combined with UE cloud improve the accuracy by 13.2% compared to BI-RADS alone for all lesions, 23.2% for <10mm lesions, 13.3% for ≥10-20mm lesions, 6.3% for ≥20mm lesions, 18.4% for <50 years group, 1.7% for ≥50 years group, 13.7% for northern area group, 17.7% for southern area group and 4.4% for western area group.
The help which UE contributed to BI-RADS was greater for breast lesions <10mm and <50 years group.
No preview · Article · Aug 2015 · European journal of radiology
[Show abstract][Hide abstract] ABSTRACT: The numbering up of microchannel reactors definitely faces great challenge in uniformly distributing fluid flow in every channel, especially for multiphase systems. A model of stochastic differential equations (SDEs) is proposed based on the experimental data recorded by a long term optical measurement to well quantify the stochastic trajectories of gas bubbles and liquid slugs in parallel microchannels interconnected with two dichotomic distributors. The expectation and variance of each sub flow rate are derived explicitly from the SDEs associated with the Fokker-Planck equation and solved numerically. A bifurcation in the trajectory is found by using the original model, then a modification on interactions of feedback and crosstalk is introduced, the evolutions of sub flow rates calculated by the modified model match well with experimental results. The established methodology is helpful for characterizing the flow uniformity and numbering up the microchannel reactors of multiphase system. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Using environmental wastes to produce energy materials is extremely attractive for economic social development. Herein, sludge flocs (SF), a kind of environmental wastes which are difficult to be disposed, were used as carbon and nitrogen source for the preparation of N-doped mesocellular graphene foam (SF-NMGF) via a simple one-step pyrolysis. Originated from the special composition and structure of SF, the obtained SF-NMGF had large Brunauer-Emmett-Teller surface areas, graphitic frameworks surrounded by ultrathin nanosheets, foam-like mesopores with size centered at about 15 nm, and homogeneous nitrogen incorporation with high percentage (40.5 at%) of graphitic nitrogen. Owing to these unique properties, SF-NMGF showed excellent electrocatalytic activity with 4e as a metal-free catalyst for the oxygen reduction reaction (ORR). Specifically, the prepared SF-NMGF catalyst exhibited high diffusion-limited current, superior durability and better immunity towards methanol crossover for ORR in alkaline solution than a commercial 20 wt% Pt/C catalyst. More importantly, the synthesis of SF-NMGF can be scaled up with low cost, which will be beneficial for both the sludge handling and development of ORR materials.