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Evidence has suggested the potential of tumor-educated platelets as a biomarker trove for cancer diagnostics, but the difficulty in isolation limits its application. Since most of the circulating RNAs are derived from platelets, the change of RNA profile in platelets may lead to altered RNA expression in serum. Here, we identified a panel of platelet-associated long non-coding RNAs (lncRNAs) and evaluated its diagnostic capacity in serum of colorectal cancer (CRC) patients. Four lncRNAs, LNCAROD, SNHG20, LINC00534, and TSPOAP-AS1, were upregulated in both platelets and serum of CRC patients. A binary logistic model derived from them has validated area under roc curve of 0.78 indicating great performance. Furthermore, the expression levels of LNCAROD and TSPOAP-AS1 were correlated with cancer staging and tumor location. Together, our results add novel lncRNA biomarkers to the list of blood tests for CRC diagnostics and provide molecular evidence for the cross-talk between CRC platelets and serum.

Background Nicotinamide N-methyltransferase (NNMT) is overexpressed in various human tumors and involved in the development and progression of several carcinomas. In breast cancer, NNMT was found to be overexpressed in several cell lines. However, the clinical relevance of NNMT in breast cancer is not yet clear. Methods NNMT expression in breast carcinoma was examined by immunohistochemistry, and then, its relationship with patient clinicopathological characteristics was analyzed. The effects of NNMT on chemoresistance in breast cancer cells were assessed by cell viability, colony formation, and apoptosis assay. The NNMT, SIRT1, p53, and acetyl-p53 proteins, which are involved in NNMT-related chemoresistance, were examined by Western blotting. The SIRT1 mRNA was examined by real-time PCR, and its activity was measured by using the SIRT1 deacetylase fluorometric reagent kit. Results NNMT expression was significantly higher (53.9%) in breast carcinoma than in paracancerous tissues (10.0%) and breast hyperplasia (13.3%). A high level of NNMT expression correlated with poor survival and chemotherapy response in breast cancer patients who received chemotherapy. Ectopic overexpression of NNMT significantly inhibited the apoptotic cell death and suppression of colony formation induced by adriamycin and paclitaxel. Mechanistic studies revealed that NNMT overexpression increased SIRT1 expression and promoted its activity. Either inhibition of SIRT1 by EX527 or knockdown of SIRT1 by siRNA could reverse NNMT-mediated resistance to adriamycin and paclitaxel, which suggests that SIRT1 plays a critical role in NNMT-related chemoresistance in breast cancer. Conclusions The results of this study demonstrate a novel correlation between the NNMT expression level and patient survival, suggesting that NNMT has the potential to become a new prognostic biomarker to predict the treatment outcomes of the clinical chemotherapy in breast cancer. Moreover, targeting NNMT or downstream SIRT1 may represent a new therapeutic approach to improve the efficacy of breast cancer chemotherapy. Electronic supplementary material The online version of this article (10.1186/s13058-019-1150-z) contains supplementary material, which is available to authorized users.

Aim: To investigate the value of galectin-3 in the diagnosis of acute coronary syndrome (ACS) and the assessment of coronary artery lesions. Methodology: This study recruited 157 patients with coronary artery disease where 102 and 55 of them were subsequently grouped as ACS and non-ACS, respectively. The severity of coronary artery lesions was evaluated by Gensini score and the number of vessels involved. Results: Receiver operator characteristics analyses of galectin-3 yielded an area under the curve of 0.679 in diagnosing ACS. The galectin-3 levels were correlated with Gensini score and the number of vessels involved. Conclusion: Our study demonstrated that galectin-3 is an effective auxiliary biomarker for the diagnosis of ACS and assessment of coronary artery lesions.

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NOXA, a BH3-only proapoptotic protein involved in regulating cell death decisions, is highly expressed but short-lived in colorectal cancer (CRC). Neddylated cullin-5 (CUL5)-mediated ubiquitination and degradation of NOXA is crucial to prevent its overaccumulation and maintain an appropriate action time. However, how this process is manipulated by CRC cells commonly exposed to oxidative stress remain unknown. The peroxiredoxin PRDX1, a conceivable antioxidant overexpressed in CRC tissues, has been shown to inhibit apoptosis and TRAF6 ubiquitin-ligase activity. In this study, we found that PRDX1 inhibits CRC cell apoptosis by downregulating NOXA. Mechanistically, PRDX1 promotes NOXA ubiquitination and degradation, which completely depend on CUL5 neddylation. Further studies have demonstrated that PRDX1 oligomers bind with both the Nedd8-conjugating enzyme UBE2F and CUL5 and that this tricomplex is critical for CUL5 neddylation, since silencing PRDX1 or inhibiting PRDX1 oligomerization greatly dampens CUL5 neddylation and NOXA degradation. An increase in reactive oxygen species (ROS) is not only a hallmark of cancer cells but also the leading driving force for PRDX1 oligomerization. As shown in our study, although ROS play a role in upregulating NOXA mRNA transcription, ROS scavenging in CRC cells by N-acetyl-L-cysteine (NAC) can significantly reduce CUL5 neddylation and extend the NOXA protein half-life. Therefore, in CRC, PRDX1 plays a key role in maintaining intracellular homeostasis under conditions of high metabolic activity by reinforcing UBE2F-CUL5-mediated degradation of NOXA, which is also evidenced in the resistance of CRC cells to etoposide treatment. Based on these findings, targeting PRDX1 could be an effective strategy to overcome the resistance of CRC to DNA damage-inducing chemotherapeutics.

This paper proposes a sustainable management and decision-making model for COVID-19 control in schools, which makes improvements to current policies and strategies. It is not a case study of any specific school or country. The term one-size-fits-all has two meanings: being blind to the pandemic, and conducting inflexible and harsh policies. The former strategy leads to more casualties and does potential harm to children. Conversely, under long-lasting strict policies, people feel exhausted. Therefore, some administrators pretend that they are working hard for COVID-19 control, and people pretend to follow pandemic control rules. The proposed model helps to alleviate these problems and improve management efficiency. A customized queue model is introduced to control social gatherings. An indoor–outdoor tracking system is established. Based on tracing data, we can assess people’s infection risk, and allocate medical resources more effectively in case of emergency. We consider both social and technical feasibility. Test results demonstrate the improvements and effectiveness of the model. In conclusion, the model has patched up certain one-size-fits-all strategies to balance pandemic control and normal life.

Laboratory analysis of trace metals using inductively coupled plasma (ICP) spectroscopy is not cost effective, and the complex spatial distribution of soil trace metals makes their spatial analysis and prediction problematic. Thus, for the health risk assessment of exposure to trace metals in soils, portable X-ray fluorescence (PXRF) spectroscopy was used to replace ICP spectroscopy for metal analysis, and robust geostatistical methods were used to identify spatial outliers in trace metal concentrations and to map trace metal distributions. A case study was carried out around an industrial area in Nanjing, China. The results showed that PXRF spectroscopy provided results for trace metal (Cu, Ni, Pb and Zn) levels comparable to ICP spectroscopy. The results of the health risk assessment showed that Ni posed a higher non-carcinogenic risk than Cu, Pb and Zn, indicating a higher priority of concern than the other elements. Sampling locations associated with adverse health effects were identified as ‘hotspots’, and high-risk areas were delineated from risk maps. These ‘hotspots’ and high-risk areas were in close proximity to and downwind from petrochemical plants, indicating the dominant role of industrial activities as the major sources of trace metals in soils. The approach used in this study could be adopted as a cost-effective methodology for screening ‘hotspots’ and priority areas of concern for cost-efficient health risk management.

Mesenchymal stem cells (MSCs) have been demonstrated to be anti-inflammatory against various immune disorders through several factors, including indoleamine 2,3-dioxygenase (IDO) and TNF-stimulated gene 6 (TSG-6). However, little is known about the necessity for both of these key immunosuppressive factors. Here we employed the mouse lipopolysaccharide (LPS)-induced acute lung injury (ALI) model, and found that IDO is necessary to achieve the effect of human umbilical cord-derived MSC (hUC-MSC)-based treatment on ALI. Notably, when IDO was deleted or inhibited, the expression of TSG-6 was decreased. This specific IDO-mediated regulation of TSG-6 expression was found to be exerted through its metabolite, kynurenic acid (KYNA), as inhibition of KYNA production led to decreased TSG-6 expression. Importantly, KYNA pretreatment of human MSCs enhanced their therapeutic effect on ALI. Mechanistically, KYNA activates aryl hydrocarbon receptor (AhR), which directly binds to the TSG-6 promoter to enhance TSG-6 expression. Therefore, our study has uncovered a novel link between IDO and TSG-6, and demonstrates that a metabolite of IDO controls the TSG-6-mediated anti-inflammatory therapeutic effects of human MSCs.

Wenjing Ruan,1 Minliang Wu,2 Liuhong Shi,1 Fengying Li,3 Liangliang Dong,1 Yuanhua Qiu,1 Xiaohong Wu,1 Kejing Ying1 1Department of Respiratory Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 2Department of Laboratory, The Second Affiliated Hospital of Zhejiang University, School of Medicine, 3Department of Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, China Objective: The purpose of this study was to explore the insulin-like growth factor binding protein 7 (IGFBP7) level in the serum of chronic obstructive pulmonary disease (COPD) patients during acute exacerbation (AE).Methods: The study population consisted of 47 AECOPD patients, including 25 patients enrolled between January 2011 and February 2011 (the first group) and 22 patients enrolled from December 2011 to August 2012 (the second group) and 29 healthy controls. Chemiluminescence–linked immunoassay was used to detect serum IGFBP7 levels. For the second group patients, IGFBP7 and C-reactive protein (CRP) levels were measured both on the admission day and on the discharge day.Results: Among the first group AECOPD patients, serum IGFBP7 levels were significantly ­elevated in AECOPD patients in the intensive care unit (ICU; 52.92±16.32 ng/mL), and in ­hospitalized AECOPD patients not in ICU (40.66±13.9), compared to healthy subjects (30.3±7.09ng/mL; P

The aim of the present study was to explore whether Chinese learners could implicitly learn the semantic preferences of novel English words. In training, participants learned four novel verbs and were exposed to a set of verb-noun phrases that included these new words. What the participants were not told was that the use of the verbs depended on the concreteness of the nouns (i.e., the semantic preference rule). In testing, participants were required to choose between two possible verbs (one of which violated the semantic preference rule) for nouns that never occurred in training. The results showed that participants acquired unconscious knowledge of semantic preferences under incidental learning conditions, as measured by verbal reports and structural knowledge attributions. Our results provide further evidence for implicit learning of semantic preferences, suggesting that implicit learning is an important mechanism in the acquisition of L2 collocations.

Supplemental Digital Content is available in the text, To introduce the use of a new surgical approach named single-incision bilateral inguinal herniorrhaphy (SBIH) in pediatric surgical population. This was a STROBE-compliant retrospective cohort study using data from 101 patients who had undergone bilateral inguinal herniorrhaphy in our institution. Children with bilateral inguinal hernias without contraindications for surgery, ranging in age from 6 months to 12 years, were included. Fifty-six children with bilateral inguinal hernias underwent SBIH (SBIH group) and 45 patients underwent laparoscopic bilateral inguinal herniorrhaphy (LBIH) (LBIH group). Differences in operative time, postoperative pain, recurrence, and complications between the 2 groups were analyzed. Patient satisfaction with cosmetic result was also investigated using questionnaires. There were no statistically significant differences in operative time (P = .2257), postoperative pain (P = .0607), recurrence (P = .8756), and complications (P = .7467) between the 2 groups. Interestingly, the operation time of girls in SBIH group was significantly shorter than that of the boys in this group (P

ObjectivesOur aim was to assess the release level of heparin-binding protein (HBP) in sepsis and septic shock under theThird International Consensus Definitions for Sepsis and Septic Shock(Sepsis-3).DesignProspective cohort study.SettingA general teaching hospital in China.ParticipantsAdult infected patients with suspected sepsis and people who underwent physical examination were included. According to the health status and severity of illness, the research subjects were divided into healthy, local infection, sepsis non-shock and septic shock under Sepsis-3 definitions.Main outcome measuresPlasma levels of HBP, procalcitonin (PCT), C reactive protein (CRP) and complete blood count were detected in all subjects. Single-factor analysis of variance was used to compare the biomarker levels of multiple groups. A receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of each marker.ResultsHBP levels were significantly higher in patients with sepsis non-shock than in those with local infections (median 49.7ng/mL vs 11.8 ng/mL, pConclusionsA high level of HBP in plasma is associated with sepsis, which might be a useful diagnostic marker in patients with suspected sepsis.

Nicotinamide N-methyltransferase (NNMT), which converts nicotinamide to 1-methylnicotinamide (1-MNA), is overexpressed in a variety of human cancers and serves as a potential anti-cancer target. In this study, we investigated the effect of NNMT on 5-fluorouracil (5-FU) sensitivity of colorectal cancer (CRC) cells, and the underlying mechanisms. Our results show that down-regulation of NNMT in CRC HT-29 cells diminishes 5-FU resistance, while over expression of NNMT in SW480 cells enhances it. NNMT reduces reactive oxygen species (ROS) production induced by 5-FU by increasing 1-MNA in CRC cells. The reduction in ROS leads to inactivation of the ASK1-p38 mitogen-activated protein kinase (MAPK) pathway, which reduces 5-FU-induced apoptosis. In vivo, NNMT attenuates 5-FU-induced inhibition of CRC tumor growth in nude mice. These observations suggest that NNMT and the 1-MNA it produces inhibit the ASK1-p38 MAPK pathway, resulting in increased CRC cell resistance to 5-FU.

Background Urinary tract infections (UTIs) are the second most frequently encountered nosocomial infectious diseases, and they greatly increase the cost of medical care and prolong the duration of hospital stays. Aim We aimed to evaluate the performance of the Sysmex UF-1000i analyser for the rapid prediction of UTIs in hospitalized patients with or without indwelling catheters at a comprehensive teaching hospital that encounters complex disease types. Methods Urine specimens ( n = 1016) were cultured and examined for WBC, RBC, bacteria (BACT) and yeast-like cell (YLC) count using the Sysmex UF-1000i. The results were compared with the urine culture results. Receiver operating characteristic curve analysis was applied to determine BACT and YLC cutoff values for bacterial and fungal UTIs independently. The diagnostic ability of the UF-1000i was also compared for patients with and without indwelling catheters. Findings A cutoff value of 38.7/μL was acceptable for ruling out bacterial UTIs. In this setting, we achieved a sensitivity of 90%, a negative predictive value of 94.5%, a false negative rate of 2.85% (29 cases), and avoided culturing in 52% of the samples. The BACT count presented a larger area under the curve for patients with indwelling catheters than for those without (0.939 vs. 0.861); however, no significant difference in the diagnostic ability of the two curves was found. Conclusion The Sysmex UF-1000i analyser could be a reliable method for excluding bacterial UTIs in hospitalized patients with or without urinary catheters and could help clinicians determine whether antibiotic therapy is necessary.

The aim of this study was to establish a method for predicting heavy metal concentrations in PM1 (aerosol particles with an aerodynamic diameter ≤ 1.0 μm) based on back propagation artificial neural network (BP-ANN) and support vector machine (SVM) methods. The annual average PM1 concentration was 26.31 μg/m3 (range: 7.00–73.40 μg/m3). The concentrations of most metals were higher in winter and lower in autumn and summer. Mn and Ni had the highest noncarcinogenic risk, and Cr the highest carcinogenic risk. The hazard index was below safe limit, and the integrated carcinogenic risk was less than precautionary value. There were no obvious differences in the simulation performances of BP-ANN and SVM models. However, in both models many elements had better simulation effects when input variables were atmospheric pollutants (SO2, NO2, CO, O3 and PM2.5) rather than PM1 and meteorological factors (temperature, relative humidity, atmospheric pressure and wind speed). Models performed better for Pb, Tl and Zn, as evidenced by training R and test R values consistently >0.85, whereas their performances for Ti and V were relatively poor. Predicted results by the fully trained models showed atmospheric heavy metal pollution was heavier in December and January and lighter in August and July of 2019. For the period covering the COVID-19 outbreak in China, from January to March 2020, most of the predicted element concentrations were lower than in 2018 and 2019, and the concentrations of nearly all metals were lowest during the nationwide implementation of countermeasures taken against the pandemic., Graphical abstract Image 1, Highlights • No noncarcinogenic or carcinogenic risk resulted from inhalation of metals in PM1. • Many metals had better simulation effects when atmospheric pollutants as inputs. • BP-ANN and SVM models both performed better for Pb, Tl and Zn than for Ti and V. • Predicted metal contents were lower during COVID-19 outbreak than in 2018 or 2019.

Recent investigations revealed that macrophages could be trained with an altered responsiveness, raising the possibility of combating autoimmune diseases by imparting anti-inflammatory capabilities to these cells. While investigating the effect of mesenchymal stem cells on experimental autoimmune encephalomyelitis (EAE), we found a critical role of insulin-like growth factor 2 (IGF-2) in training macrophages to become anti-inflammatory during their maturation. IGF-2 exerts its effects by preprogramming maturing macrophages to commit oxidative phosphorylation (OXPHOS). IGF-2-preprogrammed macrophages maintained the mitochondrial complex V activities even upon pro-inflammation stimulation, thus enabling an elevated programmed death-ligand 1 (PD-L1) expression. PD-L1 neutralization abolished the beneficial effect of IGF-2 on EAE. Furthermore, adoptive transfer of IGF-2-preprogrammed macrophages to EAE mice increased Tregs and alleviated the diseases. Our results demonstrate that shaping macrophage responsiveness by IGF-2 is effective in managing inflammatory diseases, and the OXPHOS commitment can be preset to determine the anti-inflammatory fate of macrophages.

Haze caused by high particulate matter loadings is an important environmental issue. PM2.5 was collected in Nanjing, China, during a severe haze-fog event and clear periods. The particulate-bound elements were chemically fractionated using sequential extractions. The average PM2.5 concentration was 3.4 times higher during haze-fog (96-518 μg/m(3)) than non-haze fog periods (49-142 μg/m(3)). Nearly all elements showed significantly higher concentrations during haze-fog than non-haze fog periods. Zn, As, Pb, Cd, Mo and Cu were considered to have higher bioavailability and enrichment degree in the atmosphere. Highly bioavailable fractions of elements were associated with high temperatures. The integrated carcinogenic risk for two possible scenarios to individuals exposed to metals was higher than the accepted criterion of 10(-6), whereas noncarcinogenic risk was lower than the safe level of 1. Residents of a city burdened with haze will incur health risks caused by exposure to airborne metals.

Two cAMP signaling compartments centered on adenylyl cyclase (AC) exist in human airway smooth muscle (HASM) cells, one containing β

Comprehensive bioinformatics analyses were performed to explore the key biomarkers in response to HIV infection of CD4

Nicotinamide N-methyltransferase (NNMT), an enzyme involved in the biotransformation and detoxification of many drugs and xenobiotic compounds, has been found to be overexpressed in several malignancies, including colorectal cancer. However, the biological function of NNMT and the related mechanisms in colorectal cancer have not been elucidated. In the present study, we investigated the effects of NNMT on tumorigenesis by overexpressing NNMT in the human colorectal cancer cells line SW480 which lacks constitutive NNMT expression, and downregulating NNMT expression in HT-29 cells, which exhibit high endogenous expression of NNMT. We found that NNMT significantly accelerates cell proliferation, enhances colony formation in vitro and tumorigenicity in mice; it also inhibits apoptosis, promotes cell cycle progression, increases ATP and 1-methylnicotinamide level and decreases ROS level. We also showed that 1-methylnicotinamide accelerates cell growth, inhibits apoptosis, promotes cell cycle progression, attenuates ROS production and increases ATP level. Our results indicate that NNMT enhances the capacity of tumorigenesis associated with the inhibition of cell apoptosis and the promotion of cell cycle progression in human colorectal cancer cells and the 1-methylnicotinamide increased by NNMT mediates the cellular effects of NNMT in cells. NNMT may play a vital role in energy balance and ROS induction.

Previous research has shown that perceptual information such as font size has an impact on learners' judgments of their own learning. The present study extended the font-size effect to examine the influence of font size on how people decide which items to study first. Across three experiments, we showed that participants preferred to first select items presented in a large font size (48 pt) more than items presented in a small font size (18 pt), and that this effect continued even when more diagnostic cues (difficulty and reward value of items) were presented, suggesting that perceptual cues can strongly influence control process involved in self-regulated learning. These results provide evidence that perceptual information plays a key role in higher cognition. Moreover, our results also suggest that control processes are influenced by multiple cues, including font size, difficulty of items, and the reward value of items.

Recent studies suggested that the ovarian cancers with negative excision repair cross-complementation group 1 enzyme (ERCC1) expression have a better response to platinum-based chemotherapy than those with positive ERCC1 expression. The objective of this study was to evaluate whether ERCC1 expression is associated with response to platinum-based chemotherapy in ovarian cancers. MEDLINE, PubMed, Web of Science and CNKI databases were used for searching studies relating to ERCC1 protein expression and response to platinum-based chemotherapy in ovarian cancers. Statistical analysis was based on the method for a fixed effects meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals for ERCC1 protein expression and response to platinumbased chemotherapy were generated. Publication bias was investigated with Begg’s test. Five studies involving 306 patients with ovarian cancer were included. Compared to patients with positive ERCC1 expression, those with negative ERCC1 expression had a better response to platinum-based chemotherapy. The pooled OR was 5.264 (95% CI: 2.928 – 9.464, P < 0.001) and publication bias was not found (P = 0.904). The result was similar in both in Asians and Caucasians (P < 0.001 and P = 0.028, respectively). ERCC1 protein expression status is significantly associated with response to platinum-based chemotherapy in ovarian cancers.

Mammalian mesenchymal stem cells (MSCs) have been shown to be strongly immunosuppressive in both animal disease models and human clinical trials. We have reported that the key molecule mediating immunosuppression by MSCs is species dependent: indoleamine 2,3-dioxygenase (IDO) in human and inducible nitric oxide synthase (iNOS) in mouse. In the present study, we isolated MSCs from several mammalian species, each of a different genus, and investigated the involvement of IDO and iNOS during MSC-mediated immunosuppression. The characterization of MSCs from different species was by adherence to tissue culture plastic, morphology, specific marker expression, and differentiation potential. On the basis of the inducibility of IDO and iNOS by inflammatory cytokines in MSCs, the tested mammalian species fall into two distinct groups: IDO utilizers and iNOS utilizers. MSCs from monkey, pig, and human employ IDO to suppress immune responses, whereas MSCs from mouse, rat, rabbit, and hamster utilize iNOS. Interestingly, based on the limited number of species tested, the iNOS-utilizing species all belong to the phylogenetic clade, Glires. Although the evolutionary significance of this divergence is not known, we believe that this study provides critical guidance for choosing appropriate animal models for preclinical studies of MSCs.

Previous research has shown that people can implicitly acquire mappings between word forms and literal meanings (Williams, 2004, 2005). We argue, from the metaphor-representation and embodiment perspectives, that people can unconsciously establish mappings between word forms and not only literal but also metaphorical meanings. Using Williams' (2005) paradigm, we found that transfer of form-meaning connections from a concrete domain (space) to an abstract domain (power) was achieved in a metaphor-consistent way without awareness. Our results support the view that unconscious knowledge can be flexibly deployed in an abstract way not previously explored in the implicit learning literature.

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Aims: To determine whether circulating multiple miRNAs can be used as novel biomarkers for the diagnosis in breast cancer, we performed a systematic review and meta-analysis. Materials & methods: After searching the databases of PubMed, EMBASE and Web of Science, we used the bivariate meta-analysis model to summarize the diagnostic indices and plot the summary receiver operator characteristic curve. Results: The summary estimates revealed that the pooled sensitivity was 88% (95% CI: 82–93%); specificity was 84% (95% CI: 74–91%); positive likelihood ratio was 4.69 (95% CI: 2.93–7.51); negative likelihood ratio was 0.15 (95% CI: 0.09–0.25); diagnostic odds ratio was 38.21 (95% CI: 13.41–108.85); and the area under the curve was 0.93 (95% CI: 0.90–0.95). Conclusion: These results suggested that circulating multiple miRNAs might serve as novel biomarkers for breast cancer, with a relatively high level of accuracy.

Visfatin was recently identified as an adipocytokine and has insulin mimetic properties, but its role in adolescents remains largely unknown. In this study, we examined the impact of adolescent obesity on circulating visfatin levels and the relationship between visfatin and anthropometric indices, insulin sensitivity, and blood lipids in Chinese adolescents (11-18 years). Serum visfatin, adiponectin, leptin, and blood lipids were measured in 76 non-obese and 72 obese adolescents. The medians of serum visfatin levels were significantly higher in obese subjects of 34.68ng/ml than in non-obese subjects of 28.67ng/ml (P=0.002). There were no significant correlations in the non-obese group between the serum visfatin concentration and the anthropometric indices or the lipid parameters. However, visfatin levels were negatively correlated with age, early insulin secretion index (EISI), Tanner stage, and positively correlated with HDL-c in the obese adolescents. These relationships, except that for EISI and Tanner stage, remained significant (P0.05) after adjusting for age, gender, and body mass index. Moreover, unlike adiponectin and leptin, visfatin concentration did not correlate with testosterone in non-obese and obese boys. In conclusion, visfatin levels may decrease with age and be related to the HDL metabolism in obese adolescents.

Long non-coding RNAs (lncRNAs) have been demonstrated to regulate metabolic tissue development and function, including adipogenesis, hepatic lipid metabolism, islet function and energy balance. However, the role of lncRNAs in gluconeogenesis remains completely unknown. Metformin reduces glucose output mainly via the inhibition of gluconeogenesis. In the present study, the lncRNA expression profile of primary mouse hepatocytes exposed to cyclic adenosine monophosphate (cAMP), a gluconeogenic stimulus, with or without metformin was analyzed by microarray. Among the 22,016 lncRNAs that were identified, 456 were upregulated and 409 were downregulated by cAMP (fold-change ≥2.0). Furthermore, the cAMP-induced upregulation of 189 lncRNAs and downregulation of 167 lncRNAs was attenuated by metformin. The expression levels of eight lncRNAs were validated by reverse transcription-quantitative polymerase chain reaction, and the results were consistent with those of the microarray analysis. Among them, two lncRNAs NR_027710 and ENSMUST00000138573, were identified to have an association with two protein coding genes, namely peroxisome proliferator-activated receptor-γ coactivator-1α, a critical transcriptional coactivator in gluconeogenesis, and G protein-coupled receptor 155, respectively. The two protein coding genes exhibited similar expression patterns to their associated lncRNAs. The findings of the present study suggest that lncRNAs are potentially involved in the regulation of gluconeogenesis.

Background Like adults, children need to allocate study time and endeavour optimally in order to enhance learning effectiveness. Aims The aim of this study was to investigate the development of shifting from habitual to agenda-based processes on study decisions. Sample The participants were 309 children in the second, fourth, and sixth grades. Methods We adopted the research paradigm proposed by Ariel and Dunlosky (2013, Mem. Cognit., 41, 416). In Experiment 1, the students selected items to study either with or without time constraint. In Experiment 2, the students were instructed to select all three items or one item to study per trial. Results The results of Experiment 1 showed that for sixth graders, the likelihood of selecting high-value items under the restricted-study-time condition was higher than that under the restricted-total-time condition; second and fourth graders failed to construct an agenda of prioritizing high-reward items for study in the restricted-study-time condition. In Experiment 2, when students were instructed to select one item to study per trial, high-value items were prioritized over items on the left of the array for sixth graders; on the contrary, second and fourth graders seemed to choose item for study arbitrary, although they tend to choose high-value items compared with their choice pattern in no-choice-limit condition. Conclusions The results indicate that children can shift towards agenda-based process when habitual responding cannot maximize reward, and there is an age-related improvement in shifting between grade 4 and grade 6.

This meta-analysis aimed to evaluate whether an association exists between the ERCC1 rs11615 (C>T) polymorphism and patient response to platinum-based chemotherapy and radiation-based chemotherapy. Publications were selected from PubMed and MEDLINE. A meta-analysis was conducted to determine the association between genetic polymorphisms and response to platinum-based chemotherapy and radiation-based chemotherapy by checking the odds ratios (ORs) and 95 % confidence intervals (CIs). In our overall analysis, the ERCC1 rs11615 (C>T) polymorphism was not associated with response to platinum-based chemotherapy in five comparison models. In the subgroup analyses by ethnicity, the ERCC1 rs11615 (C>T) polymorphism was shown to be significantly associated with objective response in Caucasian patients treated with platinum-based chemotherapy in the recessive model (TT vs. CT/CC: OR 0.696, 95 % CI 0.508–0.954, heterogeneity = 0.330), but the association was not observed in the Asian population. The C allele was significantly associated with better response to radiochemotherapy in the recessive model comparison (TT vs. CC/CT: OR 0.724, 95 % CI 0.585–0.869, heterogeneity = 0.008). Subgroup analysis by cancer type revealed that the C allele of ERCC1 rs11615 predicted a better response in esophageal cancers in two comparison models (T vs. C: OR 0.756, 95 % CI 0.648–0.880, heterogeneity = 0.653; TT vs. TC/CC: OR 0.457, 95 % CI 0.306–0.684, heterogeneity = 0.723). Stratified analysis by ethnicity showed a better response in Caucasians in allelic comparison model (T vs. C: OR 0.895, 95 % CI 0.819–0.977, heterogeneity = 0.095). Together, our results suggest that the ERCC1 rs11615 (C>T) polymorphism was associated with therapeutic response in Caucasian patients and C allele of ERCC1 rs11615 could represent a genetic molecular marker to predict better patient response to radiochemotherapy in recessive model. However, larger prospective randomized trials will be required.

Introduction Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are biomarkers for ovarian cancer. Their specificity and sensitivity are often limited during pregnancy as a result of great fluctuations. The risk of ovarian malignancy algorithm (ROMA) score, which combines CA125, HE4, and menopausal status, may improve diagnostic performance. There are no reports regarding the ROMA index in pregnant women. Therefore, the aim of our study was to establish appropriate reference intervals (RIs) for the ROMA index in pregnant Chinese women and compare them with those of CA125 and HE4 during pregnancy. Methods Serum concentrations of CA125 and HE4 were simultaneously measured in healthy pregnant women via electrochemiluminescence immunoassay (ECLIA). The ROMA index was calculated using premenopausal algorithms. Results The RIs for the ROMA index calculated by premenopausal algorithms were substantially closer to the normal range in the first 2 trimesters. For pregnant women, the great misclassifications identified in CA125 may be reversed by the use of ROMA index. Conclusions We established the RIs for HE4 and CA125, as well as the ROMA index, in pregnant women at different gestational periods. The ROMA index is suggested to be a more promising tumor marker for pregnant women diagnosed with malignance.

Background CA 19-9 is one of the most frequently used biomarkers for tumors. Methods We analyzed the influential factors of the Carbohydrate Antigen 19-9 (CA 19-9) levels in Chinese general population to better interpret the results of the CA 19-9 screening tests. 36,924 apparently healthy individuals and 1,335 patients with gastrointestinal (GI) tumors were involved in this study. Serum CA 19-9 levels were measured using a Roche Cobas E601. Results The serum CA 19-9 levels in apparently healthy individuals were correlated with age and gender. Its level was positively correlated with the age of males, while it showed a V-shape curve in female populations. This effect could be due to sex hormones, such as prolactin, which were found to have a negative effect on the level of CA 19-9 in the present study. Conclusions Our data indicates that gender and age could affect the CA19-9 serum level. We can set up different cut-off values according to the patient's gender and age, which can help us to get a more individualized representation in different populations.

People can implicitly learn a connection between linguistic forms and meanings, for example between specific determiners (e.g. this, that...) and the type of nouns to which they apply. Li et al (2013) recently found that transfer of form-meaning connections from a concrete domain (height) to an abstract domain (power) was achieved in a metaphor-consistent way without awareness, showing that unconscious knowledge can be abstract and flexibly deployed. The current study aims to determine whether people transfer knowledge of form-meaning connections not only from a concrete domain to an abstract one, but also vice versa, consistent with metaphor representation being bi-directional. With a similar paradigm as used by Li et al, participants learnt form- meaning connections of different domains (concrete vs. abstract) and then were tested on two kinds of generalizations (same and different domain generalization). As predicted, transfer of form-meaning connections occurred bidirectionally when structural knowledge was unconscious. Moreover, the present study also revealed that more transfer occurred between metaphorically related domains when judgment knowledge was conscious (intuition) rather than unconscious (guess). Conscious and unconscious judgment knowledge may have different functional properties.

BACKGROUND: To date, the available non-invasive remedies for primary aldosteronism are not satisfactory in clinical practice. The phosphoinositide 3-kinase (PI3Ks)/protein kinase B (PKB or AKT)/mammalian target of rapamycin (mTOR) signaling pathway is essential for tumorigenesis and metastasis in many types of human tumors, including renal cancer, adrenal carcinoma and pheochromocytoma. The possibility that this pathway is also necessary for the pathogenesis of primary aldosteronism has not yet been explored. To answer this question, we investigated the activity of the PI3K/AKT/mTOR signaling pathway in normal adrenal glands (NAGs), primary aldosteronism (PA) patients and NCI-H295R cells. METHODOLOGY/PRINCIPAL FINDINGS: Between January 2005 and December 2011, we retrospectively reviewed the records of 45 patients with PA. We compared clinical characteristics (age, gender and biochemical data) and the expression of phospho-AKT (p-AKT), phospho-mTOR (p-mTOR), phospho-S6 (p-S6) and vascular endothelial growth factor (VEGF) by immunohistochemical staining and western blotting, analyzing 30 aldosterone-producing adenomas (APAs), 15 idiopathic hyperaldosteronism (IHA) tissues and 12 NAGs following nephrectomy for renal tumors (control group). Compared with the control group, most of the PA patients presented with polydipsia, polyuria, resistant hypertension, profound hypokalemia, hyperaldosteronemia and decreased plasma renin activity. Compared with normal zona glomerulosa, the levels of p-AKT, p-mTOR, p-S6 and VEGF were significantly upregulated in APA and IHA. No significant differences were found between APA and IHA in the expression of these proteins. Additionally, positive correlations existed between the plasma aldosterone levels and the expression of p-AKT and p-mTOR. In vitro studies showed that mTOR inhibitor rapamycin could inhibit cell proliferation in NCI-H295R cells in a dose- and time-dependent manner. Furthermore, this inhibitor also decreased aldosterone secretion. CONCLUSIONS: Our data suggest that the PI3K/AKT/mTOR signaling pathway, which was overactivated in APA and IHA compared with normal zona glomerulosa, may mediate aldosterone hypersecretion and participate in the development of PA.

To investigate the ING1 gene mutation status in human laryngeal squamous cell carcinoma(LSCC), and the association of p33(ING1b) protein expression with p53 protein expression.DNA of LSCC tissue was extracted, and nucleotide of the second exon was amplified and sequenced to determine the chromosome status. The p23(ING1b) and p53 protein expression were detected by immunohistochemistry and the association between them were analyzed.No mutation was detected in ING1 gene, but a single polymorphism from GGG to AGG at codon 170 of ING1 gene was found in 2 of the 25 LSCC tissues. The immunohistochemical analysis showed that 4 had positive p33(ING1b) expression. No association was found between p33(ING1b) expression and LSCC clinical features, or between p53 and clinical features. However, significant difference was found between p33(ING1b) and p53 expression. p33(ING1b) tended to be negative in p53 expression positive tissue.ING1 gene mutation appears rare in LSCC. In normal physical condition, p33(ING1b) may play a synergistic effect with p53 protein.

Although a growing number of empirical studies have revealed that activating mate-related motives might exert a specific set of consequences for human cognition and behaviors, such as attention and memory, little is known about whether mate-related motives affect self-regulated learning. The present study examined the effects of mate-related motives (mate-search and mate-guarding) on study-time allocation to faces varying in attractiveness. In two experiments, participants in mate-related priming conditions (Experiment 1: mate-search; Experiment 2: mate-guarding) or control conditions studied 20 female faces (10 highly attractive, 10 less attractive) during a self-paced study task, and then were given a yes/no face recognition task. The finding of Experiment 1 showed that activating a mate-search motive led the male participants to allocate more time to highly attractive female faces (i.e., perceived potential mates) than to less attractive ones. In Experiment 2, female participants in the mate-guarding priming condition spent more time studying highly attractive female faces (i.e., perceived potential rivals) than less attractive ones, compared to participants in the control condition. These findings illustrate the highly specific consequences of mate-related motives on study-time allocation, and highlight the value of exploring human cognition and motivation within evolutionary and self-regulated learning frameworks.

To measure the serum highly sensitive C-reactive protein (hs-CRP) and adiponectin levels, assess insulin sensitivity index (SI) and acute insulin response (AIR) in normal control (NC) subjects, patients with impaired glucose tolerance (IGT) and newly diagnosed type 2 diabetes mellitus (DM), and further explore the possible correlation between hs-CRP and SI, AIR and adiponectin in IGT and newly diagnosed type 2 DM groups.Age and sex matched 28 normal subjects, 31 patients with IGT, and 31 patients with newly diagnosed type 2 DM were included in the study. SI and AIR were assessed by the reduced sample number of Bergman's minimal model method with intravenous glucose tolerance test in subjects of each group.Compared with NC group, serum hs-CRP was significantly increased in IGT and type 2 DM groups (p0.001), although there was no significant difference between the latter groups. Hs-CRP was negatively correlated with high density lipoprotein cholesterol (HDL-C), SI and adiponectin levels (p0.05 to p0.001), and positively correlated with systolic blood pressure (SBP), fasting plasma glucose (FPG), BMI, waist-to-hip ratio (WHR), postprandial 2h plasma glucose (2hPG), fasting serum insulin (FINS) and postprandial serum insulin (PSI) in IGT and newly diagnosed type 2 DM groups (p0.05 to p0.001). In general multivariate regression, only adiponectin was the significantly independent determinant for serum hs-CRP (regression coefficient -1.380; 95% CI -2.062 to 0.698, p0.001); meanwhile, TG, SI, hs-CRP, FINS, 2hPG and WHR were significantly independent determinants for serum adiponectin concentration (p0.05 to p0.001).Elevated serum hs-CRP may play a role in the development of insulin resistance syndrome and type 2 diabetes. This elevation is accompanied by the opposite changes of adiponectin.

The action of berberine was compared with metformin and troglitazone (TZD) with regard to the glucose-lowering action in vitro. HepG2 cell line, phenotypically similar to human hepatocytes, was used for glucose consumption (GC) studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. In moderate high glucose concentration (11.1 mmol/L), GC of HepG2 cells was increased by 32% to 60% (P

To investigate the effects of glucocorticoids and insulin on serum leptin level and its diurnal rhythmicity in patients with Cushing's syndrome and obesity as well as in normal subjects.Fifteen patients with Cushing's syndrome and 10 with obesity as well as 9 normal subjects were investigated, with their serum leptin, cortisol and insulin levels measured 6 times a day (8:00, 12:00, 16:00, 20:00, 24:00, 3:00).The diurnal rhythmicity of serum leptin was still preserved in all the three groups, with peak appearing at 24:00 approximately 3:00 and nadir at 8:00 approximately 12:00. However, the relative diurnal excursion was negatively correlated with body mass index (BMI). The peak positive effects of insulin on leptin secretion delayed by 4 to 8 hours.Glucocorticoids can increase serum leptin levels, but the changes of the diurnal rhythmicity of cortisol do not affect the diurnal rhythmicity of leptin. The relative diurnal excursion of leptin is negatively correlated with body fat, i.e, the fatter subjects usually have the blunter leptin diurnal rhythmicity. Insulin exerts an effect on leptin secretion in a delayed manner, indicating its role in maintaining the diurnal rhythmicity of serum leptin.