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Holliday junction recognition protein (HJURP) is involved in the regulation of mortality in various cell types, including renal cell carcinoma (RCC) cells. The specific mechanisms by which HJURP regulates RCC cell apoptosis and the cell cycle have not been previously investigated, to the best of our knowledge. In the present study, the expression of HJURP in RCC tissues and adjacent paracancerous renal tissue, as well as in RCC cell lines, was analyzed using reverse transcription‑quantitative PCR and western blot analysis. The A498 RCC cells were transfected with an HJURP overexpression vector, which resulted in reduced proliferation, as demonstrated using immunofluorescence staining, a Cell Counting Kit‑8 assay and a colony formation assay. Flow cytometry and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labelling assays were used to determine the effect of HJURP on the cell cycle and apoptosis of RCC cells. Proteins associated with the reactive oxygen species (ROS) status were analyzed using western blot analysis. The expression of HJURP was lower in RCC tissues and cells compared with that in the adjacent paracancerous renal tissues and control cells. Furthermore, overexpression of HJURP resulted in a decrease in cell viability and proliferation in vitro. Overexpression of HJURP resulted in cell cycle arrest at the G0/G1 phase, cell apoptosis and an increase in ROS stress. In addition, the phosphorylated/total sirtuin 1 (SIRT1) protein ratio was decreased, whereas the expression of peroxisome proliferator‑activated receptor (PPAR)γ was increased in the HJURP‑overexpressing RCC cells. In clinical practice, decreased HJURP expression may be associated with poor prognosis in patients with RCC. These results suggest that HJURP may regulate cell apoptosis and proliferation in RCC cells and this may be mediated by PPARγ/SIRT1. Thus, HJURP may be used as a predictor of prognosis in patients with RCC.

To improve the mechanical behavior of core wall in higher embankment dams, soil–rock mixture obtained by mixing rock blocks to the cohesive soil is used for the first time as the core wall material of the Nuozhadu embankment dam, China. The differences in the mechanical behavior of soil and soil–rock mixture samples are studied in depth. Two large-scale compaction test fields and a series of in-situ direct shear tests have been conducted on soil and soil–rock mixture samples. The mixing of rock blocks changes the deformation behavior of the sample. The existence of rock blocks makes the deformation modulus and the internal friction angle of soil–rock mixture greater than that of the soil sample, while decreasing its cohesive force.

The deformation and failure mechanism and the mechanical behavior of soil and soil-rock mixture used in an embankment dam was studied using numerical testing, based on a discrete element method (DEM). In this work, a 3D random meso-structure modelling system of soil-rock mixture is developed and used to generate a meso-structural model of soil-rock mixture. A non-overlapping combination method was used to model convex polyhedron rock blocks for the DEM numerical simulation. Based on the Voronoi cell, a method representing volume strain at particle scale is proposed. Results show that there is close contact between macro mechanical behavior and deformation localization of the sample. Rotation, occlusion, dilatation and a self-organizing force chains are remarkable phenomena of the localization band, and occur simultaneously with localization. Rock blocks influence localization characteristics and distribution of the force chains of the soil-rock mixture sample. Rotation and overcoming of the occlusion of the larger rock blocks in the localization band are more difficult than for small soil particles, which is the important reason for higher shear strength of soil-rock mixture than that of soil. The shearing process leads to anisotropy of the contact force, reaching its maximum at the start point of the plastic deformation, and then begins to decrease in the subsequent process.

The dynamic time-history response analysis method was employed to analyze the dynamic response of composition foundation with CFG piles. The deformation and stress distribution of composite foundation of CFG piles with different length and amount of piles under seismic wave was investigated. The results reveal that the bearing and asti-deformation capacity could be improved effectively for composite foundation under earthquake loads by increasing the length and number of pile. The vertical stress of foundation soil decreases gradually with the increase of the length and number of pile. The practice shows that CFG piles provide a positive contribution to the aseismic effect of foundation soils mass. The present research can provide some references to similar projects.

An incrementally nonlinear hypoplastic constitutive model was introduced, which was developed without recourse to the concepts in elastoplasticity theory such as yield surface, plastic potential and the decomposition of the deformation into elastic and plastic parts. Triaxial drained tests on rockfill were conducted on a large scale triaxial apparatus under two types of stress paths, which were the stress paths of constant stress ratio and the complex stress paths with transitional features. Motivated by the effect of stress path, the Gudehus-Bauer hypoplastic model was improved by considering the parameter variations with different ratios of stress increment. Fitting parameter α presents a piecewise linear relationship with cosine of the slope angle θ determined by instantaneous stress path. The improved hypoplastic model can present peak stress increasing and volumetric strain changing from dilatancy to contractancy with the increase of transitional confining pressure σ3t and the decrease of slope angle θ of stress path. Compared with the test data, it is shown that the model is capable of fully considering the effect of stress path on rockfill.

Objective: To explore the effects of dexamethasone (DXM) and vincristine (VCR) on cytosine arabinoside (Ara-C) induced apoptosis and activation of nuclear factor-K-gene binding (NF-κB) in leukemic cell line HL60-n. Methods: Apoptosis of HL60-n cells was analysed by TdT-mediated X-dUTP nick and end labeling (TUNEL) and DNA electrophoresis. NF-κB activity of HL60-n cells was detected by electrophoretic mobility shift assay (EMSA). Results: There was slight activation of NF-κB in HL60-n cells without drug induction. Ara-C at 1 (µmol/L significantly enhanced the activation of NF-κB in HL60-n cells. The level of NF-κB activation induced by DXM at 1 µmol/L or VCR at 0.1 µmol/L had no significant difference compared with that of the control group. However, in HL60-n cells pre-treated with 1 µmol/L of DXM or 0.1 µmol/L of VCR, the activation of NF-κB induced by 1 µmol/L of Ara-C was significantly suppressed with inhibition rates of 31.0% and 47.0%, respectively. The apoptosis rates of HL60-n cells induced by 1.0 µmol/L, 10 µmol/L and 100 µmot/L Ara-C were 45.00±3.16%, 61.88±3.40% and 77.62±4.75%, respectively. The apoptotic rates of HL60-n cells induced by DXM at 1 µmol/L or VCR at 0.1 µmol/L were similar to that of the control group. However, either DXM at 1 µmol/L or VCR at 0.1 µmol/L could enhance the apoptosis of HL60-n cells induced by Ara-C at 1 µmol/L with rates of 39.1 % and 59.2%, respectively. Conclusion: Ara-C can induce apoptosis and activation of NF-κB in HL60-n cells. The mechanism of increased apoptosis of HL60-n cells by DXM or VCR may be related to suppression of NF-κB activation.

To explore the effects of dexamethasone (DXM) and vincristine (VCR) on apoptosis of K562-n cells and activation of nuclear factor-kappaB-gene binding (NF-kappaB) in K562-n cells induced by homoharringtonine.K562-n cells were cultured in RPMI-1640 medium. Homoharringtonine of various concentrations was added into the cultures. Twelve hours later, the apoptosis induced by homoharringtonine in K562-n cells was analysed by TdT-mediated X-dUTP nick and end labeling (TUNEL) and DNA electrophoresis. Another sample of K562-n cells was culture together with DXM (1 micro mol/L) or VCR (0.1 micro mol/L) for 2 hours, then homoharringtonine was added into the cultures. Twelve hours later, the apoptosis in K562-n cells was analysed by TUNEL and DNA electrophoresis. Still another sample of K562-n cells was cultured for 3 hours with homoharringtonine, then electrophoretic mobility shift assay (EMSA) was conducted to determine the DNA-binding activation of NF-kappaB. A fourth sample of K562-n cells was cultured together with DXM (1 micro mol/L) or VCR (0.1 micro mol/L) for 2 hours, then homoharringtonine was added into the cultures. Three hours later, EMSA was conducted.The apoptosis rates of K562-n cells induced by homoharringtonine of various concentrations were (30.00 +/- 3.34)%, (47.13 +/- 3.18)% and (68.63 +/- 8.14)%, respectively. The apoptosis rates of K562-n cells induced by homoharringtonine being pre-processed with DXM or VCR were (55.75 +/- 3.88)% and (64.38 +/- 4.60)%, respectively, being 85.8% and 114.6% higher than that induced by homoharringtonine alone (30.00 +/- 3.34)% (all P0.05). Activation of NF-kappaB in K562-n cells was induced significantly by homoharringtonine. Activation of NF-kappaB in K562-n cells induced by homoharringtonine could be suppressed by being pre-processed with 1.0 micro mol/L DXM or 0.1 micro mol/L VCR. The rate of suppression was 32.0% and 39.4% respectively.Homoharringtonine induces apoptosis of K562-n cells and induces NF-kappaB activation in K562-n cells. The mechanism of increased apoptosis of K562-n cells with DXM or VCR may be related to suppression of activation of NF-kappaB of K562-n cells.

To analyze the relation between activation of NF-kappa B and chemotherapy induced apoptosis of leukemic cells and the effect of vincristine (VCR) on them.Electrophoretic mobility shift assay (EMSA) was used to detect the activation of NF-kappa B and tunel DNA electrophoresis was adopted to observe the apoptosis induced by cytosine arabinoside (Ara-C) and etopside (Vp-16) in P388 leukemic cells.The activation of NF-kappa B induced by Ara-C and Vp-16 was obviously correlated to apoptosis in P388 cells. VCR (0.1 micromol/L) could suppress activation of NF-kappa B by 52% and 63% and significantly increase the apoptosis by 89% and 123% as induced by Ara-C (100 micromol/L) and Vp-16 (100 micromol/L). The activity of NF-kappa B could be found in P388 cells before being exposed to chemotherapeutic agent.Chemotherapeutic agents can induce apoptosis and activation of NF-kappa B of P388 cells. The mechanism of VCR potentiating chemotherapeutics induction of leukemia cell apoptosis may be related to its suppression of the NF-kappa B activity in the P388 cells.

To construct the multi-probe ribonuclease protection assay (RPA) template set to be used for detecting expression patterns of MD-2, TLR4, CD14 mRNAs in human peripheral blood mononuclear cells.The designed cDNA fragments of the three genes were generated by polymerase chain reaction (PCR) using specific primers and directionally cloned into EcoR I and Hind III sites of expression plasmid pSP72 containing the T7 promoter, the linearized plasmids was used as template to synthesize anti-sense RNA probes. Then we extracted total RNA from peripheral blood mononuclear cells (PBMC) and detected the dynamic expression patterns of the three genes with RPA method.The proper sequence and orientation of the template set were confirmed by sequencing and the template set was successfully used to assay TLR4, MD-2 and CD14 mRNAs in human PBMC. The results showed that the three detected genes decreased transiently 1-3 hours after 100 ng/ml LPS stimulation.These new RPA multi-probe set provided valuable tool for the simultaneous quantitative determination of expression of TLR4, CD14 and MD-2 mRNAs in both constitutive and inducible types.

The abnormal proliferation of vascular smooth muscle cells (VSMCs) is closely related to vascular diseases. There is growing evidence that calcium antagonists inhibit VSMC growth/proliferation, yet their molecular mechanisms remain to be determined. Recent reports suggest that p42/p44 mitogen-activated protein kinases (MAPKs) play an important role in cell growth and proliferation induced by growth factors. This study was designed to determine whether these MAPKs are involved in VSMC proliferation induced by basic fibroblast growth factor (bFGF) and to examine the inhibitory effect of amlodipine. Human VSMCs were obtained from inner mammary artery. p42/p44 MAPKs activity was measured by immunoblotting assay using anti-p42/p44 phospho-MAPK antibody. 1) bFGF (20 ng/ml) significantly activated p42/p44 MAPKs with a peak time of 5-15 min, which was maintained for 3 h. PD98059 (100 nM-10 microM), a specific inhibitor of MAPK kinase, inhibited bFGF-induced p42/p44 MAPKs activation in a dose-dependent manner. 2) Amlodipine (1-100 nM) dose-dependently inhibited p42/p44 MAPKs activation by bFGF. 3) Amlodipine (10 nM) could inhibit both short-term and long-term p42/p44 MAPKs activation by bFGF. Our results indicate that bFGF could activate p42/p44 MAPKs. Amlodipine, which could inhibit bFGF-induced human VSMC proliferation, inhibited both short-term and sustained p42/p44 MAPKs activation by bFGF, suggesting that bFGF-induced VSMC proliferation may be related to p42/p44 MAPKs activation, and that the antiproliferative effect of amlodipine may be related to its inhibition of p42/p44 MAPKs activation.

To evaluate the risk factors for invasive bladder cancer and to develop a predictive model for the improvement of individual comprehensive therapy for invasive bladder cancers. The records of 356 patients with invasive bladder cancer, operated on at three Chinese medical institutes, were reviewed. The Cox proportional hazards regression model was used to assess the clinical and pathological variables affecting disease-free survival (DFS). The regression coefficients determined by Cox regression analysis were used to construct a predictive index (PI). PI was used to categorize the patients into different risk groups. Kaplan–Meier survival curves followed with log-rank test were plotted to compare the difference. Tumor configuration (RR = 1.60, P = 0.01), multiplicity (RR = 1.41, P = 0.04), histological subtype (RR = 2.13, P