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Melatonin receptor type 1 (MTNR1A or MT1) is known to play an important role in cancer progression; however, its prognostic value for resected gastric adenocarcinoma (RGA) is unknown. In this study, we examined the potential of MT1 as a prognostic biomarker for RGA. The expression of the MT1 was evaluated in 67 patients with RGA by immunohistochemistry, and the relationship between MT1 levels and RGA prognosis was analyzed by Chi-square test, multivariate Cox regression, Kaplan-Meier method, and log-rank test. High MT1 expression was associated with a poor survival rate (29.0%, p=0.002) and the occurrence of metastasis (62.9%, p=0.004). Kaplan-Meier survival analysis and log rank tests revealed that patients with high expression of the MT1 had significantly shorter median overall survival compared to those with low expression (33.0 vs. 65.0 months, respectively; p=0.02). Multivariate Cox analysis indicated that the calculated death risk (hazard ratio [HR]) in patients with high expression levels of the MT1 increased to 2.68 (95% confidence interval [CI] 1.21-5.94, p=0.015), which was higher compared to those with low levels. HR of death was also high in patients with advanced T stage (2.51; 95 % CI 1.00-6.26, p=0.049) and metastasis (5.02; 95% CI 1.94-13.03, p=0.001). Our results showed that high MT1 expression in primary gastric adenocarcinoma tissues was associated with the occurrence of metastasis and poor prognosis. It may have prognostic significance as a potential biomarker in patients with RGA.

Cytokine signal transduction inhibitor 3 (SOCS3) negatively regulates Janus kinases (JAK) - signal transducer and activator of transcription (STAT) pathway. Bioinformatics analysis revealed a targeted relationship between miR-203 and SOCS3 mRNA. This study investigated the role of miR-203 in ovarian cancer cell proliferation and apoptosis.Ovarian cancer tissues and adjacent tissues were collected to detect the expression of miR-203 and SOCS3. Ovarian cancer HO8910 cells were divided into miR-NC group, miR-203 inhibitor group, and miR-203 mimic group followed by the analysis of the expression of miR-203 and SOCS3 mRNA by quantitative Reverse Transcription-PCR (qRT-PCR), protein expression of p-JAK2 and p-STAT3 by Western blot, cell apoptosis by flow cytometry, and proliferation by 5-Ethynyl-2'-deoxyuridine (EdU) staining chronologically.Compared with adjacent tissues, miR-203 expression was significantly increased in tumor tissues and SCOS3 mRNA expression was decreased. Compared with those with lower miR-203 expression, the prognosis of patients with higher expression of miR-203 was significantly worse. There was a targeted regulatory relationship between miR-203 and SOCS3 mRNA. Compared with IOSE80 cells, miR-203 expression in HO8910 and SKOV3 cells was increased, and its expressions of SOCS3 mRNA and protein were decreased. Compared with miR-NC group, the transfection of miR-203 inhibitor significantly increased SOCS3 expression, and decreased the expression of p-JAK2 and p-STAT3 protein. We draw the conclusion that miR-203 increased cell apoptosis and decreased cell proliferation. However, opposite results were observed after the transfection of miR-203 mimic.Abnormal miR-203 and SOCS3 expression are related to the pathogenesis of ovarian cancer. MiR-203 affects the proliferation of JAK-STAT pathway and regulates the proliferation and apoptosis of ovarian cancer cells by targeting the inhibition of SOCS3 expression.

High-precision response of the surrogate model is desired in the process of optimisation. An excessive number of sampling points will increase the cost of the calculation. The appropriate number of sampling points cannot only guarantee the accuracy of the surrogate model but also save the calculation cost. The purpose of this research is to demonstrate the eventuality of using an adaptive surrogate model for optimisation problems. The adaptive surrogate model is built on an adaptive sampling approach and an extended radial basis function (ERBF). The adaptive sampling is an approach that new sampling points are placed in the blank area and all the sampling points are uniformly distributed in the design region using Multi-Island GA. The precision of the ERBF surrogate model is checked using standard error measure to determine whether the surrogate model should be updated or not. This adaptive surrogate model is used to optimise a cruise missile head shape. Aerodynamic and stealthy performance of the cruise missile head shape are considered in this research. Different global objective function and different weight factor are used to research the aerodynamic and stealthy performance in this optimisation process. The results show that the drag is reduced with a slender head shape and the radar-cross section (RCS) value is reduced with a short head shape.

Electron spin resonance spectral parameters (g factors g‖, g⊥ and hyper ne structure constants A‖, A⊥) of a tetragonal V centers in MB4O7 (M = Zn, Cd) are theoretically investigated by using the perturbation formulae for a 3d ion in tetragonally compressed octahedra. In these formulae, the contributions to the g factors from the tetragonal distortion, characterized by the tetragonal eld parameters Ds and Dt are taken into account by considering the local structures of the ligand octahedron around the V due to the Jahn Teller e ect. Based on the calculations, the ligand octahedra around V are suggested to su er about 5.7% and 4.3% relative compression along C4 axis for MB4O7 glasses with M = Zn and Cd, respectively, and negative signs of the hyper ne structure constants A‖ and A⊥ for V 4+ centers in MB4O7 glasses were suggested in the discussion.

To investigate the association between different kinds of systolic blood pressure (SBP, including office, visit-to-visit, 24-hour ambulatory) and vascular damages (represented by carotid intima-media thickness, CIMT; brachial-ankle pulse wave velocity, baPWV) in the elderly.A total of 2 814 participants aged of ≥60 years old and retired employees were selected with random sampling method from the individuals who took part in 2006-2007, 2008-2009, 2010-2011 health examination in Tangshan Kailuan Hospital, Kailuan Linxi Hospital, Kailuan Zhaogezhuang Hospital and with 24-hour ambulatory blood pressure monitoring data, CIMT and baPWV.Finally, 2 146 participants (1 438 males, average age (67.3±6.0) years old) were included to the analysis.Multivariable regression analysis was used to analyze association between the office, visit-to-visit, 24-hour, day-time, night-time SBP and CIMT and baPWV, respectively.(1) The average SBP, DBP, CIMT and baPWV were (137.0±20.4) mmHg(1 mmHg=0.133 kPa), (83.5±11.0) mmHg, (0.92±0.18)mm and (1 781.7±353.2)cm/s.(2) The participants were divided into high and low level groups according to the median of different SBPs, respectively.The results indicated that CIMT and baPWV were significantly higher in high level groups than in low level groups (all P0.01). (3) After adjusting for gender and age, the partial correlate analysis showed that the office, visit-to-visit, 24-hour, day-time, night-time SBP positively associated with CIMT and baPWV (all P0.01). (4) After adjusting for confounding factors, multivariable regression analysis showed that the office, visit-to-visit, 24-hour, day-time, night-time SBP were positively and linearly associated with CIMT and baPWV in total cohort, and standard regression coefficients were 0.157, 0.208, 0.175, 0.169, 0.163, 0.479, 0.420, 0.401, 0.389 and 0.354, respectively.In addition, similar results were observed in male and female participants but there was no significance between night-time SBP and CIMT in female participants.Office, visit-to-visit, 24-hour, day-time, night-time SBP are associated with vascular damages, and the best associations are observed between visit-to-visit SBP and vascular function damage.Chinese CLINICAL TRIAL REGISTRY, ChiCTR-TNC-1100 1489.

To investigate the optimal anticoagulation methods and monitoring strategy for Chinese patients undergoing heart valve replacement, which is potentially quite different from western populations.In this multicenter prospective cohort study, the anticoagulation and monitoring strategy data was acquired from 25 773 in-hospital patients in 35 medical centers and 20 519 patients in outpatient clinic in 11 medical centers from January 1st, 2011 to December 31th, 2015.As for in-hospital patients, mean age of study population was (48.6±11.2) years old; main etiology of valve pathology was rheumatic (87.5%) origin among study cohort; 94.8% of study population received mechanical valve implantation; international normalized ratio (INR) monitoring (in all the study centers) and low-intensity anticoagulation strategy (31 hospitals chose target INR range of 1.5-2.5, and actual values of INR among 89.2% of 100 069 in-hospital monitoring samples were 1.5-2.5), with mean actual INR values of 1.84±0.53, and warfarin dosage of (2.82±0.93) mg/d were widely adopted among the study centers; strategies of in-hospital warfarin administration were similar in all the study centers; complication rates of low-intensity anticoagulation strategy were low in severe hemorrhage (0.02%), thrombosis (0.05%), and thromboembolism (0.05%) events, without anticoagulation-related death.As for 18 974 outpatient clinic patients, the follow-up rate was 92.47%, with a total of 30 012 patient-years (Pty). Anticoagulation-related morbidity and mortality rates were 0.67% and 0.15% Pty; major hemorrhage morbidity and mortality rates were 0.25% and 0.13% Pty; thromboembolism morbidity and mortality rates were 0.45% and 0.03% Pty.The mean dosage of warfarin daily dosage was (2.85±1.23) mg/d and INR value was 1.82±0.57.No significant regional difference in the intensity of anticoagulation therapy was noted during the study.INR can be used as a normalized indicator for intensity of anticoagulation therapy in China.The optimal anticoagulation intensity with INR range from 1.5 to 2.5 is safe and effective for Chinese patients with heart valve replacement, and there is no significant regional difference in the intensity of anticoagulation therapy.

To investigate the distribution and influencing factors of orthostatism brachial-ankle pulse wave velocity(baPWV) and ankle brachial index(ABI) in the elderly.Participants were selected with random sampling from ≥60 years old retired workers, who underwent 2010 to 2011 health check-up in the Tangshan Kailuan Hospital, Kailuan Linxi Hospital, Kailuan Zhaogezhuang Hospital. Multivariate linear regression analysis was used to analyze the influencing factors of orthostatism and supine baPWV and ABI in the elderly.(1) A total of 2 464 participants were included, and 1 601 participants (1 065 males(66.5%) and (67.5±6.1) years old) with integral data were analyzed. Orthostatism baPWV was (3 885.4±1 503.5)cm/s and Supine baPWV was (1 761.2±371.4)cm/s.Orthostatism ABI was 1.54±0.21 and supine ABI was 1.10±0.12. Orthostatism baPWV increased with increasing age, while orthostatism ABI decreased with aging(trend test, both P0.01)in65, 65-69, 70-74, and ≥75 years old participants.(2) Multiple linear regression analysis showed that the age(β=0.19, P0.01), lower limbs orthostatism systolic blood pressure(β=0.18, P0.01), lower limbs supine systolic blood pressure (β=0.14, P0.01), orthostatism heart rate (β=0.30, P0.01), supine heart rate (β=0.23, P0.01), body mass index (β=-0.18, P0.01) were associated with orthostatism baPWV, and female(β=-0.055, P=0.01), upper limb orthostatism systolic blood pressure (β=-0.834, P0.01), lower limbs orthostatism systolic blood pressure (β=0.708, P0.01), lower limbs supine systolic blood pressure (β=0.099, P0.01) and fasting blood glucose(β=-0.085, P0.01) were associated with orthostatism ABI.Orthostatism baPWV and ABI were significantly higher than those of supine's. Age, lower limbs orthostatism and supine systolic blood pressure, orthostatism and supine heart rate, body mass index were associated with orthostatism baPWV. Female, upper limb orthostatism systolic blood pressure, lower limbs orthostatism, supine systolic blood pressure and fasting blood glucose were associated with orthostatism ABI in the elderly.

We wished to evaluate the association between expression of microRNA (miR) -503 and prognosis in patients with cervical cancer.96 paired specimens of cervical cancer and adjacent normal cervical epithelial tissues were obtained. qPCR was used to evaluate expression levels of miR-503. We analyzed the associations between miR-503 expression levels and clinicopathological parameters, as well as recurrence-free and overall survival with Kaplan-Meier survival curves and proportional hazards model.miR-503 levels were significantly (p0.001) lower in cervical cancer tissue compared with adjacent normal cervical epithelial tissue. We further observed significant associations of expression of this miR and recurrence of cervical cancer, lymph node metastasization, and International Federation of Gynecology and Obstetrics (FIGO) stage. In addition, in multivariate analysis, miR-503 expression level was found to be an independent prognostic factor for both recurrence-free and overall survival.Reduced expression of miR-503 is an independent prognostic factor in cervical cancer indicating poor prognosis.

On the basis of the perturbation formulas for a $d^{1}$ configuration ion in a tetragonal crystal field, the three optical absorption bands and electron paramagnetic resonance (EPR) parameters ($g$ factors $g_{i}$ and hyperfine structure constants $A_{i}$ for $i = \|$ and $\perp$, respectively) of VO$^{2+}$ in Na$_{3}$C$_{6}$H$_{5}$O$_{7}\cdot2$H$_{2}$O single crystals were studied using the perturbation theory method. By simulating the calculated optical and EPR spectra to the observed values, local structure parameters and negative signs of the hyperfine structure constants $A_{i}$ of the octahedral (VO$_{6}$)$^{8-}$ cluster in trisodium citrate dehydrate single crystal can be obtained., Comment: 5 pages

In this study, we developed a model of sperm in vitro differentiation to study the mechanism of spermatogenesis. We isolated newborn male germ cells for in vitro differentiation. We found that after 4-5 weeks of culture, sperm-like cells were occasionally observed in cell co-culture and the feed-layer. After 1-2 weeks of culture followed by 4-5 weeks of co-culture, sperm-like cells were observed.

In a real construction project, the duration and cost of each activity could change dynamically as a result of many uncertain variables, such as weather, resource availability, productivity, etc. Managers/planners must take these uncertainties into account and provide an optimal balance of time and cost based on their own experience and knowledge. In this paper, fuzzy sets theory is applied to model the managers’ behavior in predicting time and cost pertinent to a specific option within an activity. Genetic algorithms are used as a searching mechanism to establish the optimal time–cost profiles under different risk levels. In addition, the nonreplaceable front concept is proposed to assist managers in recognizing promising solutions from numerous candidates on the Pareto front. Economic analysis skills, such as the utility theory and opportunity cost, are integrated into the new model to mimic the decision making process of human experts. A simple case study is used for testing the new model developed. In...

Time–cost optimization (TCO) is one of the greatest challenges in construction project planning and control, since the optimization of either time or cost, would usually be at the expense of the other. Although the TCO problem has been extensively examined, many research studies only focused on minimizing the total cost for an early completion. This does not necessarily convey any reward to the contractor. However, with the increasing popularity of alternative project delivery systems, clients and contractors are more concerned about the combined benefits and opportunities of early completion as well as cost savings. In this paper, a genetic algorithms ( GAs ) -driven multiobjective model for TCO is proposed. The model integrates the adaptive weight to balance the priority of each objective according to the performance of the previous “generation.” In addition, the model incorporates Pareto ranking as a selection criterion and the niche formation techniques to improve popularity diversity. Based on the pr...

Reducing both project cost and time (duration) is critical in a competitive environment. However, a trade-off between project time and cost is required. This in turn requires contracting organizations to carefully evaluate various approaches to attaining an optimal time-cost equilibrium. Although several analytical models have been developed for time-cost optimization (TCO), they mainly focus on projects where the contract duration is fixed. The optimization objective in those cases is therefore restricted to identifying the minimum total cost only. With the increasing popularity of alternative project delivery systems, clients and contractors are targeting the increased benefits and opportunities of seeking an earlier project completion. The multiobjective model for TCO proposed in this paper is powered by techniques using genetic algorithms (GAs). The proposed model integrates the adaptive weights derived from previous generations, and induces a search pressure toward an ideal point. The concept of the GA-based multiobjective TCO model is illustrated through a simple manual simulation, and the results indicate that the model could assist decision-makers in concurrently arriving at an optimal project duration and total cost.

Backward Raman amplification was observed in a 0.7 mm-long high-density gas jet plasma. The 800 nm 30 fs seed pulse was amplified by a factor ~28, with an output energy of 2.8 mJ. The output spectra showed that the waveband around 800 nm was significantly amplified. The experimental result demonstrated that the resonant Raman amplification can be realized in high-density plasma against strong plasma instability.

To investigate the effect of cavernous nerve injury on the nNOS-containing nerve fibers in rat corpus cavernosum.Thirty-three male SD rats were randomized into 3 groups: 5 rats underwent pelvic exploration without transection of cavernous nerve as the sham-operated controls, the unilateral injury group (14 rats) had the cavernous nerve cut on one side, and the bilateral injury group (14 rats) had the nerves cut on both sides. Corpora cavernosa were harvested at the 3rd week and 6th month after surgery. nNOS-positive nerve fibers were examined with strepavidin peroxidase immunohistochemistry techniques (SP method).After bilateral ablation, the nNOS-positive nerve fibers were significantly decreased at both the 3rd week (17 +/- 4) and the 6th month (16 +/- 4). For the unilateral injury group, the nNOS-positive nerve fibers were similarly decreased on the side of the neurotomy at the 3rd week (18 +/- 6), but by the 6th month, the number increased significantly (61 +/- 9) and approximated the level on the contralateral side (81 +/- 13).In rats after unilateral cavernous nerve ablation, nNOS-containing nerve fibers might regenerate 6 months after operation, but regeneration did not occur in animals with bilateral cavernous nerve injury. Results suggest that during pelvic radical surgery, the cavernous nerve should be preserved at least on one side in order to accomplish adequate regeneration.

To investigate the effect of androgen on the structure of corpus cavernosum.Thirty mature rats were randomized into 3 groups, i.e., simple castration, castration with testosterone (T) supplementation and sham-operated controls. One week after operation, the animals were sacrificed and corpora cavenosa harvested. Apoptosis was detected with the in situ end labeling (ISEL) techniques and DNA fragment analysis.The apoptotic rate was 4.19% in the simple castrated rats, 0. 2% in castrated rats supplemented with T and 0.14% in the controls. Significant difference was found between the simple castrates and other two groups (P0.01). When comparing the T-supplementation group with the controls, there was no statistical difference (P0.05).Castration induced apoptosis in rat corpus cavernosum, that could be prevented by T supplementation. It suggests that androgen plays an important role in maintaining the structure of corpus cavernosum.

Anti-c-Src and anti-phosphotyrosine immunoprecipitates from receptor-like protein tyrosine phosphatase alpha (PTP alpha)-transfected and control rat embryo fibroblasts contain a 39-kDa phosphoprotein (p39) whose phosphorylation is enhanced by PTP alpha expression. The p39 that co-immunoprecipitates with c-Src has been identified as c-Jun by immunological and functional criteria; it is recognized by several different anti-c-Jun antibodies and binds to a c-Jun recognition element-containing oligonucleotide. Whereas the association of c-Src and c-Jun is unexpected, it may be of significance in PTP alpha signaling since we have previously demonstrated that c-Src is activated by PTP alpha (Zheng, X. M., Wang, Y., and Pallen, C. J. (1992) Nature 359, 336-339. Examination of c-Jun activity in these fibroblasts demonstrates that c-Jun DNA binding activity and c-Jun-mediated transcription of a chloramphenicol acetyltransferase reporter gene are elevated in PTP alpha-expressing cells. In addition to c-Jun activation, mitogen-activated protein kinase is activated in PTP alpha-expressing cells and translocated to the nuclei of these cells. The nuclear localization of activated mitogen-activated protein kinase and c-Jun suggests that their activation represents downstream events in the receptor-like PTP alpha-initiated signaling pathway(s).

On the basis of 124 cases of homologous-cartilage grafts, the changes of host's tissue structure and immune active cells around the homologous-cartilage were studied. Slices of implantation at different time were investigated by histologic, histochemical, immunopathologic and ultrastructural methods. The results show that the rejection phenomena of homologous-cartilage grafts may be the process of substitution of bone for cartilage, rather than the process of absorption and there are no influences on supporting framework of homologous-cartilage grafts.

THE initiation of transcription of eukaryotic genes involves the ordered assembly of a multiprotein complex on proximal promoter elements such as the TATA box1,2. In addition to RNA polymerase II (otherwise RNA pol II, RNA polymerase B), four general transcription factors are required for initiation of transcription3–6: BTF1 (also referred to as TFIID) which has recently been cloned from yeast7–11, BTF2, BTF3 and STF. The first step in assembly of the initiation complex is the stable binding of BTF1 to the TATA box12–15, which is facilitated by STF. Neither BTF2 nor BTF3 bind directly to the promoter proximal elements, but BTF3 can form a stable complex with RNA pol II (ref. 6). We recently purified BTF3 (ref. 6), which is a protein of relative molecular mass 27,000, but further studies have been hampered by its low abundance in cells. On the basis of sequences from peptides of BTF3, we have now cloned two complementary DNAs, one for a protein (BTF3a) with all the characteristics of purified BTF3, and one for a shorter protein (BTF3b) lacking the first 44 residues of BTF3a and which is transcriptionally inactive, despite its ability to bind RNA pol II.

This paper reports a case of AIDS whose first symptom was SAE. The main clinic characteristics were epilepsy, and brain atrophy. In addition, there were also other features in this case, such as multiorgan damage, weight loss, fever and diarrhea. The patient's serum showed a positive result to anti HTLV-III, and TH:Ts = 0.22 less than 1. According to the direct pathogenic effect of HIV on CNS, which is similar to SV, we made the diagnosis that it was the first case of SAE of AIDS in China. We also made a preliminary exploration into the cause of low Ig in the case.

The fate of human cartilage allografts and the mechanism of its kinetical development were studied histopathologically and immunohistologically. After transplantation, the grafts underwent necrosis, calcification and were partially invaded by osteoplastic tissue of the host and eventually replaced by bone tissue. Thus, the contour of the transplanted cartilage was kept partially by the living cartilage and the newly-formed osseous tissue. The grafts were surrounded initially by granular tissue and then by scar tissue, in which numerous T cells and a few macrophage infiltrates were noted. In T cells, T4+ lymphocytes predominated but T8+ cells accounted for a small number. B cells were not found within the infiltrates. Most of the infiltrating cells expressed 12 antigens, indicating that the majority of T cells were activated. It was concluded that T lymphocytes mediated cellular immunity played an important role. The chondrocytes of the cartilage did not express HLA I and II antigens before transplantation, but one month later, the living chondrocytes became HLA I and II antigens positive, and the antigen expression became stronger with the elapse of time; this might be induced by lymphokins, especially by interferon produced by the infiltrating lymphocytes. Such an expression of MHC antigens on chondrocytes might contribute to the further enhancement of immunorejection.