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The behavioral activation system (BAS) and the behavioral inhibition system (BIS) have been proposed to relate to stable traits that predict inter-individual differences in motivation. Prior reports point dopamine (DA) pathways, mainly including ventral tegmental area (VTA) and substantia nigra (SN), implicate in subserving reward-related functions associated with BAS and inhibitory functions related with BIS. However, as an important factor that affects DA releasing, it remains an open question whether the ovarian hormones may also be related to BIS/BAS. Here, to investigate effects of the estradiol (E2) and progesterone (PROG) on BIS/BAS and related DA pathways, we employed a BIS/BAS scale and the resting-state functional magnetic resonance imaging (fMRI) during the late follicular phase (FP) and the mid-luteal phase (LP). On the behavioral level, when women had high PROG levels, their E2 levels were found positively correlated with BIS scores, but those women whose PROG levels were low, their E2 levels were negative correlation with BIS scores. On the neural level, we demonstrated BAS was related with the VTA pathway, included brain reward regions of nucleus accumbens (NAc) and orbitofrontal cortex (OFC). Meanwhile, the BIS was correlated with the SN-dorsolateral prefrontal cortex (dlPFC) pathway. ROI-based resting-state functional connectivity (RSFC) analyses further revealed that, RSFC between the SN and dlPFC was modulated by ovarian hormones. With higher PROG levels, increased E2 levels among women were accompanied by stronger RSFC of the SN-dlPFC, but when PROG levels were low, E2 levels were negatively correlated with the SN-dlPFC RSFC. These findings revealed a combined enhancement effect of E2 and PROG on BIS, and the SN-dlPFC pathway was mainly involved in this process. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of carbon nanoparticles in identifying sentinel lymph nodes in early-stage cervical cancer. Methods: From January 2014 to January 2016, 40 patients with cervical cancer stage IA2–IIA, based on the International Federation of Gynecology and Obstetrics (FIGO) 2009 criteria, were included in this study. The normal cervix around the tumor was injected with a total of 1 mL of carbon nanoparticles (CNP)at 3 and 9 o'clock. All patients then underwent laparoscopic pelvic lymph node dissection and radical hysterectomy. The black-dyed sentinel lymph nodes were removed for routine pathological examination and immunohistochemical staining. Results: Among the 40 patients, 38 patients had at least one sentinel lymph node (SLN). The detection rate was 95% (38/40). One hundred seventy-three SLNs were detected with an average of 3.9 SLNs per side. 25 positive lymph nodes, which included 21 positive SLNs, were detected in 8 (20%) patients. Sentinel lymph nodes were localized in the obturator (47.97%), internal lilac (13.87%), external lilac (26.59%), parametrial (1.16%), and common iliac (8.67%) regions. The sensitivity of the SLN detection was 100% (5/5), the accuracy was 97.37% (37/38), and the negative predictive value was 100. 0% and the false negative rate was 0%. Conclusions: Sentinel lymph nodes can be used to accurately predict the pathological state of pelvic lymph nodes in early cervical cancer. The detection rates and accuracy of sentinel lymph node were high. Carbon nanoparticles can be used to trace the sentinel lymph node in early cervical cancer. [ABSTRACT FROM AUTHOR]

Spines or trichomes on the fruit of cucumbers enhance their commercial value in China. In addition, glabrous mutants exhibit resistance to aphids and therefore their use by growers can reduce pesticide residues. Previous studies have reported two glabrous mutant plants containing the genes, csgl1 and csgl2. In the present study, a new glabrous mutant, NCG157, was identified showing a gene interaction effect with csgl1 and csgl2. This mutant showed the glabrous character on stems, leaves, tendrils, receptacles and ovaries, and there were no spines or tumors on the fruit surface. Inheritance analysis showed that a single recessive gene, named csgl3, determined the glabrous trait. An F2 population derived from the cross of two inbred lines 9930 (a fresh market type from Northern China that exhibits trichomes) and NCG157 (an American processing type with glabrous surfaces) was used for genetic mapping of the csgl3 gene. By combining bulked segregant analysis (BAS) with molecular markers, 18 markers, including two simple sequence repeats (SSR), nine insertion deletions (InDel) and seven derived cleaved amplified polymorphism sequences (dCAPs), were identified to link to the csgl3 gene. All of the linked markers were used as anchor loci to locate the csgl3 gene on cucumber chromosome 6. The csgl3 gene was mapped between the dCAPs markers dCAPs-21 and dCAPs-19, at genetic distances of 0.05 cM and 0.15 cM, respectively. The physical distance of this region was 19.6 kb. Three markers, InDel-19, dCAPs-2 and dCAPs-11, co-segregated with csgl3. There were two candidate genes in the region, Csa6M514860 and Csa6M514870. Quantitative real-time PCR showed that the expression of Csa6M514870 was higher in the tissues of 9930 than that of NCG157, and this was consistent with their phenotypic characters. Csa6M514870 is therefore postulated to be the candidate gene for the development of trichomes in cucumber. This study will facilitate marker-assisted selection (MAS) of the smooth plant trait in cucumber breeding and provide for future cloning of csgl3. [ABSTRACT FROM AUTHOR]

The present study examined women's attentional bias toward ornamental objects in relation to their menstrual phase as well as to motivations of intersexual courtship or intrasexual competition. In Experiment 1, 33 healthy heterosexual women were tested in a bias-assessment visual cuing task twice: once on a high-fertility day (during the ovulatory phase) and once on a low-fertility day (during the luteal phase). They paid greater attention to pictures of ornamental objects than to pictures of non-ornamental objects near ovulation, but not during the luteal phase, suggesting an ornamental bias during the high-fertility phase. In Experiment 2, before the visual cuing task, 40 participants viewed 10 same-sex or opposite-sex facial photographs with either high or low attractiveness as priming tasks to activate the intrasexual competition or intersexual courtship motives. Results showed that women's ornamental bias was dependent on the interaction of menstrual phase and mating motive. Specifically, the ornamental bias was observed on the high-fertility day when the subjects were primed with high-attractive same-sex images (intrasexual competition) and was observed on the low-fertility day when they were primed with high-attractive opposite-sex photographs (intersexual courtship). In conclusion, the present findings confirm the hypothesis that, during the high-fertility phase, women have an attentional bias toward ornamental objects and further support the hypothesis that the ornamental bias is driven by intrasexual competition motivation near ovulation, but driven by intersexual courtship motivation during the luteal phase. [ABSTRACT FROM AUTHOR]

Attractiveness judgment in the context of mate preferences is thought to reflect an assessment of mate quality in relation to an absolute scale of genetic fitness and a relative scale of self-similarity. In this study, subjects judged the attractiveness and trustworthiness of faces in composite images that were manipulated to produce self-similar (self-resemblance) and dissimilar (other-resemblance) images. Males differentiated between self- and other-resemblance as well as among different degrees of self-resemblance in their attractiveness ratings; females did not. Specifically, in Experiment 1, using a morphing technique, we created previously unseen face images possessing different degrees (0%, 30%, 40%, or 50%) of incorporation of the subject's images (different degrees of self-resemblance) and found that males preferred images that were closer to average (0%) rather than more self-similar, whereas females showed no preference for any degree of self-similarity. In Experiment 2, we added a pro-social question about trustworthiness. We replicated the Experiment 1 attractiveness rating results and further found that males differentiated between self- and other-resemblance for the same degree of composites; women did not. Both males and females showed a similar preference for self-resemblances when judging trustworthiness. In conclusion, only males factored self-resemblance into their attractiveness ratings of opposite-sex individuals in a manner consistent with cues of reproductive fitness, although both sexes favored self-resemblance when judging trustworthiness. [ABSTRACT FROM AUTHOR]

We aimed to investigate the expressions of three Th17-associated cytokines, interleukin (IL)-17A, IL-6 and IL-23, in protein and mRNA levels and their correlations with ocular surface parameters in patients with dry eye disease (DED) through a small sample size case control study. A total of 45 female subjects were divided into Sjögren’s syndrome (SS) DED group, non-Sjögren’s syndrome (non-SS) DED group and control group. Ocular surface disease index (OSDI) was self-answered and clinical tests including tear-film breakup time (BUT), Schirmer I test, cornea fluorescein staining (CFS) were performed. The conjunctival mRNA expressions of these cytokines were investigated by real-time polymerase chain reaction (PCR) and the levels of protein in tears were measured by mutiplex bead analysis. The correlations between cytokines and ocular surface parameters were analyzed. Results show that the expressions of IL-17A and IL-6 in protein and mRNA levels were both significantly increased in the DED group (P<0.05), and also higher in SS group comparing to the non-SS group (P<0.05). Moreover, IL-17A and IL-6 correlated well with ocular surface parameters (all P<0.05, R values range from 0.5–0.8). Despite the expression of IL-23 was significantly increased in the DED group (P<0.05), there was no significant difference found between the expressions of IL-23 in SS group and non-SS group (P>0.05) and no correlation found between the IL-23 and any ocular surface parameter (P>0.05). These findings indicates that the three Th17-associated cytokines, IL-17A, IL-6 and IL-23, play roles in the pathogenesis of DED and the expressions of IL-17A and IL-6 in tears have potential to be diagnostic biomarkers for DED. [ABSTRACT FROM AUTHOR]

Background: Methylmalonic aciduria (MMA), a rare inherited disorder, is the most common organic aciduria in China, and prenatal diagnosis has contributed to its prevention. However, the prenatal diagnosis of MMA using cultured amniocytes or chorionic villi to detect gene mutations is exclusively applicable to families with a definite genetic diagnosis. To evaluate the reliability of mass spectrometry assays for the prenatal diagnosis of MMA, we conducted a retrospective study of our 10 years' experience. Materials and methods: This retrospective compare study reviewed the medical records for maternal and fetuses data for 287 mothers with a family history of MMA from June 2010 to December 2020. Methylmalonate and propionylcarnitine in cell-free amniotic fluid were measured using a stable isotope dilution method (GC/MS) and MS/MS-based method (LC/MS/MS). Total homocysteine (tHcy) was measured by fluorescence polarization immunoassay. Depending on the presence of disease-causing gene mutations in probands, gene studies on amniocytes from 222 pregnant women were performed. Results: For 222 fetuses of the families with definite genetic diagnosis, gene analyses were performed using cultured amniocytes. 52 fetuses were affected by MMA, whereas 170 were "unaffected". For GC/MS and LC/MS/MS, the specificity was 96.5% and 95.9%, sensitivity was 71.2% and 84.6%, respectively. The positive and negative predictive values were 86.0% and 91.6% and 86.3% and 95.3%, respectively. Propionylcarnitine/butyrylcarnitine ratio showed the highest accuracy and could thus serve as a sensitive indicator to identify those at a risk for MMA. When GC/MS and LC/MS/MS were performed in parallel, the specificity was 92.5% and sensitivity was 95.6%. When evaluating tHcy, the positive and negative predictive values were 95.0% and 96.1%, respectively. In 65 fetuses without family genetic diagnosis, 11 were finally confirmed to have MMA and 54 were "unaffected" by amniotic fluid biochemical assays. The 54 children showed normal urine organic acids and healthy development after birth. Conclusions: Amniotic fluid biochemical assays using GC/MS and LC/MS/MS in parallel increased the accuracy of prenatal diagnosis of MMA. Propionylcarnitine is a more reliable marker than methylmalonic acid in amniotic fluid. Further, tHcy is recommended for the prenatal diagnosis of combined MMA and homocysteinemia. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD), the most common chronic respiratory disease worldwide, not only leads to the decline of pulmonary function and quality of life consecutively, but also has become a major economic burden on individuals, families, and society in China. The purpose of this meta-analysis was to explore the risk factors for developing COPD in the Chinese population that resides in China and to provide a theoretical basis for the early prevention of COPD. Methods: A total of 2457 cross-sectional, case-control, and cohort studies published related to risk factors for COPD in China were searched. Based on the inclusion and exclusion criteria, 20 articles were selected. Stata 11.0 was used for meta-analysis. After merging the data, the pooled effect and 95% confidence intervals (CIs) were calculated to assess the association between risk factors and COPD. Heterogeneity between studies was assessed using I2 and Cochran's Q tests. Begg's test was used to assess publication bias. Results: Exposure to particulate matter less than 2.5 μm in diameter (PM2.5) (pooled effect = 1.73; 95%CI: 1.16~2.58; P <0.01), smoking history (pooled effect = 2.58; 95%CI: 2.00~3.32; P <0.01), passive smoking history (pooled effect = 1.39; 95%CI: 1.03~1.87; P = 0.03), male sex(pooled effect = 1.70; 95%CI: 1.31~2.22; P <0.01), body mass index (BMI) <18.5 kg/m2 (pooled effect = 1.73; 95%CI: 1.32~2.25; P <0.01), exposure to biomass burning emissions (pooled effect = 1.65; 95%CI: 1.32~2.06; P <0.01), childhood respiratory infections (pooled effect = 3.44; 95%CI: 1.33~8.90; P = 0.01), residence (pooled effect = 1.24; 95%CI: 1.09~1.42; P <0.01), and a family history of respiratory diseases (pooled effect = 2.04; 95%CI: 1.53~2.71; P <0.01) were risk factors for COPD in the Chinese population. Conclusion: Early prevention of COPD could be accomplished by quitting smoking, reducing exposure to air pollutants and biomass burning emissions, maintaining body mass index between 18.5 kg/m2 and 28 kg/m2, protecting children from respiratory infections, adopting active treatments to children with respiratory diseases, and conducting regular screening for those with family history of respiratory diseases. [ABSTRACT FROM AUTHOR]

3-hydroxyacyl-CoA dehydrogenase (HAD, EC 1.1.1.35) is a homodimeric enzyme localized in the mitochondrial matrix, which catalyzes the third step in fatty acid β-oxidation. The crystal structures of human HAD and subsequent complexes with cofactor/substrate enabled better understanding of HAD catalytic mechanism. However, numerous human diseases were found related to mutations at HAD dimerization interface that is away from the catalytic pocket. The role of HAD dimerization in its catalytic activity needs to be elucidated. Here, we solved the crystal structure of Caenorhabditis elegans HAD (cHAD) that is highly conserved to human HAD. Even though the cHAD mutants (R204A, Y209A and R204A/Y209A) with attenuated interactions on the dimerization interface still maintain a dimerization form, their enzymatic activities significantly decrease compared to that of the wild type. Such reduced activities are in consistency with the reduced ratios of the catalytic intermediate formation. Further molecular dynamics simulations results reveal that the alteration of the dimerization interface will increase the fluctuation of a distal region (a.a. 60–80) that plays an important role in the substrate binding. The increased fluctuation decreases the stability of the catalytic intermediate formation, and therefore the enzymatic activity is attenuated. Our study reveals the molecular mechanism about the essential role of the HAD dimerization interface in its catalytic activity via allosteric effects. [ABSTRACT FROM AUTHOR]

Aim: The long-term stress, anxiety and job burnout experienced by healthcare workers (HCWs) are important to consider as the novel coronavirus disease (COVID-19) pandemic stresses healthcare systems globally. The primary objective was to examine the changes in the proportion of HCWs reporting stress, anxiety, and job burnout over six months during the peak of the pandemic in Singapore. The secondary objective was to examine the extent that objective job characteristics, HCW-perceived job factors, and HCW personal resources were associated with stress, anxiety, and job burnout. Method: A sample of HCWs (doctors, nurses, allied health professionals, administrative and operations staff; N = 2744) was recruited via invitation to participate in an online survey from four tertiary hospitals. Data were gathered between March-August 2020, which included a 2-month lockdown period. HCWs completed monthly web-based self-reported assessments of stress (Perceived Stress Scale-4), anxiety (Generalized Anxiety Disorder-7), and job burnout (Physician Work Life Scale). Results: The majority of the sample consisted of female HCWs (81%) and nurses (60%). Using random-intercept logistic regression models, elevated perceived stress, anxiety and job burnout were reported by 33%, 13%, and 24% of the overall sample at baseline respectively. The proportion of HCWs reporting stress and job burnout increased by approximately 1·0% and 1·2% respectively per month. Anxiety did not significantly increase. Working long hours was associated with higher odds, while teamwork and feeling appreciated at work were associated with lower odds, of stress, anxiety, and job burnout. Conclusions: Perceived stress and job burnout showed a mild increase over six months, even after exiting the lockdown. Teamwork and feeling appreciated at work were protective and are targets for developing organizational interventions to mitigate expected poor outcomes among frontline HCWs. [ABSTRACT FROM AUTHOR]

The location-based services can provide users with the requested location information. But users also need to disclose their current location to the location-based service provider. Therefore, how to protect user's location privacy is a major concern. In this paper, we propose a heterogeneous deniable authenticated encryption scheme called HDAE for location-based services. The proposed scheme permits a sender in a public key infrastructure environment to transmit a message to a receiver in an identity-based environment. Our design utilizes a hybrid encryption method combing the tag-key encapsulation mechanism (tag-KEM) and the data encapsulation mechanism (DEM), which is well adopted for location-based services applications. We give how to design an HDAE scheme utilizing a heterogeneous deniable authenticated tag-KEM (HDATK) and a DEM. We also construct an HDATK scheme and provide security proof in the random oracle model. Comprehensive analysis shows that our scheme is efficient and secure. In addition, we give an application of the HDAE to a location-based services system. [ABSTRACT FROM AUTHOR]

A smart grid, considered the next-generation type of power grid, combines a traditional power grid with information and communication technologies to effectively facilitate power generation and ensure transmission security and reliability in real-time. Only authorized consumers should be able to access the smart grid because the information gathered by smart meters includes users’ private information. However, smart grid security is still a challenge. Motivated by this challenge, in this paper, we propose a heterogeneous signcryption (HSC) scheme for secure communication between smart meters and the utility. We demonstrate that this scheme is indistinguishable against adaptive chosen-ciphertext attacks (IND-CCA2), existentially unforgeable against adaptive chosen-message attacks (EUF-CMA) and ciphertext-anonymous against adaptive chosen ciphertext attacks (ANON-CCA2) under the computational Diffie-Hellman (CDH) problem in the random oracle model. Our scheme simultaneously achieves confidentiality, integrity, authentication, non-repudiation and ciphertext anonymity in a single logical step. It supports heterogeneous systems, allowing a meter in an identity-based cryptography (IBC) environment to transmit electrical usage data to a utility in a public key infrastructure (PKI) environment. Compared with other existing related schemes, our scheme has the lowest communication overhead and energy consumption for the smart grid. Based on these features, our scheme is highly suitable for secure power transmissions in a smart grid. [ABSTRACT FROM AUTHOR]

This study was to evaluate the usefulness of serum thymoglobulin (Tg) in adults to assess iodine status through a 5-year cohort study which was conducted in three regions with different levels of iodine intake: mild deficiency, more than adequate, and excess, from 1999 to 2004 in China. A total of 3099 subjects over 14 years old with normal serum levels of Tg in 1999 were eligible, of whom 2448 were followed in 2004. Serum levels of thyroid hormones and thyroid autoantibodies as well as urine iodine were measured, and B-mode ultrasonography of the thyroid was performed. A general linear model was performed to determine the determinant factors of serum Tg. Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the baseline levels of serum Tg were substantially different (7.5μg/L, 5.9μg/L, and 6.8μg/L respectively, P<0.01), which were associated with age, sex, the rate of positive TgAb, abnormal thyroid volume, abnormal TSH, and positive personal history of thyroid diseases. The data from 1856 subjects with normal range of thyroid parameters but no personal history of thyroid diseases were analyzed to clarify the effect of iodine intake on Tg. Among these three regions, the serum Tg levels were substantially different in both 1999 and 2004, with a similar pattern for increased Tg (ΔTg) (3.1μg/L, 2.5μg/L and 3.5μg/L respectively, P<0.01). The general linear model analysis revealed that age, Tg, and baseline TSH levels were the determinants of ΔTg besides iodine intake. In conclusion, serum Tg in adults, resulting from a time-accumulative effect of iodine exposure, is a useful biomarker of regional iodine intake. [ABSTRACT FROM AUTHOR]

Objective: Myocyte enhancer factor-2A (MEF 2A) has been shown to be involved in atherosclerotic lesion development, but its role in preexisting lesions is still unclear. In the present study we aim to assess the role of MEF 2A in the progression of pre-existing atherosclerosis. Methods: Eighty apolipoprotein E-deficient mice (APOE KO) were randomly allocated to control, scramble and MEF 2A RNA interference (RNAi) groups, and constrictive collars were used to induce plaque formation. Six weeks after surgery, lentiviral shRNA construct was used to silence the expression of MEF 2A. Carotid plaques were harvested for analysis 4 weeks after viral vector transduction. Inflammatory gene expression in the plasma and carotid plaques was determined by using ELISAs and real-time RT-PCR. Results: The expression level of MEF 2A was significantly reduced in plasma and plaque in the RNAi group, compared to the control and NC groups, whereas the expression level of pro-inflammatory cytokines was markedly increased. Silencing MEF 2A using lentiviral shRNA significantly reduced the plaque collagen content and fibrous cap thickness, as well as increased plaque area. However, silencing MEF 2A had no obvious effect on plaque lipid content. Conclusions: Lentivirus-mediated MEF 2A shRNA accelerates inflammation and atherosclerosis in APOE KO mice, but has no effect on lipoprotein levels in plasma. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest the higher the red blood cell distribution width (RDW) the greater the risk of mortality in patients with coronary artery disease (CAD). However, the relationship between RDW and long-term outcome in CAD patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) remains unclear. This study was designed to evaluate the long-term effect of RDW in patients treated with drug-eluting stent for CAD. Methods: In total of 2169 non-anemic patients (1468 men, mean age 60.2±10.9 years) with CAD who had undergone successful PCI and had at least one drug-eluting stent were included in this study. Patients were grouped according to their baseline RDW: Quartile 1 (RDW<12.27%), Quartile 2 (12.27%≤RDW<13%), Quartile 3 (13%≤RDW<13.5%), and Quartile 4 (RDW≥13.5). Results: The incidence of in-hospital mortality and death or myocardial infarction was significantly higher in Quartiles 3 and 4 compared with Quartile 1 (P<0.05). After a follow-up of 29 months, the incidence of all-cause death and stent thrombosis in Quartile 4 was higher than in Quartiles 1, 2, and 3 (P<0.05). The incidence of death/myocardial infarction/stroke and cardiac death in Quartile 4 was higher than in Quartiles 1 and 2 (P<0.05). Multivariate Cox regression analysis showed that RDW was an independent predictor of all-cause death (hazard ratio (HR) = 1.37, 95% confidence interval (CI) = 1.15–1.62, P<0.001) and outcomes of death/myocardial infarction/stroke (HR = 1.21, 95% CI = 1.04–1.39, P = 0.013). The cumulative survival rate of Quartile 4 was lower than that of Quartiles 1, 2, and 3 (P<0.05). Conclusion: High RDW is an independent predictor of long-term adverse clinical outcomes in non-anemic patients with CAD treated with DES. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. Methods: Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. Results: Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P = 0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P = 0.009 in multivariate analysis) or patients with proximal gastric cancer (P = 0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P = 0.052 in univariate analysis). Conclusions: Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors. [ABSTRACT FROM AUTHOR]

Background: Although general agreement exists on palliative surgery with intent of symptom palliation in advanced gastric cancer (AGC), the role of non-curative surgery for incurable, asymptomatic AGC is hotly debated. We aim to clarify the role of non-curative surgery in patients with incurable, asymptomatic AGC under the first-line chemotherapy. Methods: A total of 737 patients with incurable, asymptomatic advanced gastric adenocarcinoma between January 2008 and May 2012 at the Sun Yat-sen University Cancer Center were retrospectively analyzed, comprising 414 patients with non-curative surgery plus first-line chemotherapy, and 323 patients with first-line chemotherapy only. The clinicopathologic data, survival, and prognosis were evaluated, with propensity score adjustment for selection bias. Results: The median overall survival (OS) outcomes significantly favored non-curative surgery group over first-line chemotherapy only group in entire population (28.00 versus 10.37 months, P = 0.000), stage 4 patients (23.87 versus 10.37 months, P = 0.000), young patients (28.70 versus 10.37 months, P = 0.000) and elderly patients (23.07 versus 10.27 months, P = 0.031). The median OS advantages of non-curative surgery over first-line chemotherapy only were also maintained when the analyses were restricted to single organ metastasis (P = 0.001), distant lymph node metastasis (P = 0.002), peritoneal metastasis (P = 0.000), and multi-organ metastasis (P = 0.010). Significant OS advantages of non-curative surgery over chemotherapy only were confirmed solid by multivariate analyses before and after adjustment on propensity score (P = 0.000). Small subsets of patients with surgery of single metastatic lesion after previous curative gastrectomy, and with surgery of both primary and single metastatic sites showed sound median OS. Conclusions: There is a role for non-curative surgery plus first-line chemotherapy for incurable, asymptomatic AGC, in terms of survival. Randomized controlled trials are warranted to fill a gap in knowledge about the value of metastectomy and patient selection strategies. [ABSTRACT FROM AUTHOR]

Background: MiRNA primarily acts to repress gene expression at the post-transcriptional level through imperfect complementarity of its 5′ region to the “seed site” in the 3′ untranslated region of target mRNAs, with its “3′–supplementary site” and “center site” also playing important roles under certain circumstances. The aim of this study was to test if artificial miRNA mimics (miR-Mimics) that are designed to target the “centered sites” without “seed sites” complementarity are able to repress gene expression as natural miRNAs. Methods: We designed miR-Mimics carrying centered-site matches (CS–miR-Mimics) or seed-site matches (SS–miR-Mimics) and siRNA to two antiapoptotic genes BCL2 and AKT1. We tested the gene targeting of these constructs using real-time RT-PCR and Western blot to quantify mRNA and protein levels of BCL2 and AKT1, respectively, luciferase reporter gene assay to investigate the interaction between miR-Mimics and their target sites, and cell survival assay to study the functional outcomes of the miR-Mimics. Results: We found that CS-miR-Mimic, SS-miR-Mimic and siRNA, all down regulated the mRNA and protein levels of their cognate target BCL2 or AKT1 in a concentration-dependent manner. Luciferase reporter gene assay further confirmed the functional interactions of CS–miR-Mimic, SS-miR-Mimic and siRNA with their target sites. We then observed that the miR-Mimics and siRNAs were all able to induce cell death, as indicated by the reduced survival rate of cells. Conclusions: We have provided evidence for the feasibility of CS–miR-Mimics for post-transcriptional repression of genes, which can be designed to have reduced numbers of seed type off-target sites compared to the number of target sites from an average endogenous seed–site miRNA. CS–miR-Mimics may be a novel approach for miRNA research requiring miRNA gain-of-function. [ABSTRACT FROM AUTHOR]