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This study investigates the perception of the three Mandarin high vowels /i, u, y/ after dental, retroflex and palatal fricatives and affricates /s/-/ʦ/-/ʦʰ/; /ʂ/-/tʂ/-/tʂʰ/, and /ʨ/, /ʨʰ/, /ɕ/) by native English speakers. The results of the perceptual identification and categorization experiments show that among the three target vowels, the high front rounded vowel /y/ presents the greatest challenge for native English speakers. They have a significantly higher tendency to confuse /y/ with the Mandarin high back rounded vowel /u/ compared to the Mandarin high front unrounded vowel /i/, as they perceptually classified /y/ and /u/ into the same English vowel category /u/. The findings of the study suggest that native English speakers adopt a perceptual strategy that differs from that of native Japanese and Korean speakers, relying heavier on the feature of roundness as opposed to backness in perceiving the Mandarin /y/. This study contributes to the perceptual cue weighting field by examining the weighting of phonological cues (i.e. distinctive feature) in Mandarin high vowels by native English speakers. These results hold pedagogical significance as they highlight the importance of targeted perception training for learners of different language backgrounds to enhance both their recognition and reproduction of second language sounds.

This current research is about some new optical solitons to the time-fractional integrable generalized (2+1)-dimensional nonlinear Schrödinger (NLS) system with novel truncated M-fractional derivative. The obtained results may be used in the description of the model in fruitful way. The novel derivative operator is applied to study the aforementioned model. The achieved results are in the form of dark, bright, and combo optical solitons. The achieved solutions are also verified by using the MATHEMATICA software. The obtained solutions are explained with different plots. Modified integration methods, Exp a {{\rm{Exp}}}_{a} function, extended ( G ′ ∕ G ) \left(G^{\prime} /G) -expansion, and extended sinh-Gordon equation expansion method are applied to achieve the results. These exact solitons suggest that these methods are effective, straight forward, and reliable compared to other methods.

In this paper, a modified symbolic computation approach is proposed. The multiple rogue wave solutions of a generalized (2+1)-dimensional Boussinesq equation are obtained by using the modified symbolic computation approach. Dynamics features of these obtained multiple rogue wave solutions are displayed in 3D and contour plots. Compared with the original symbolic computation approach, our method does not need to find Hirota bilinear form of nonlinear system., Comment: 11 pages, 18 figures

Species of the spider family Leptonetidae Simon, 1890 from China are revised based on molecular and morphological data analyses. A new genus, Jingneta Wang & Li gen. nov ., is erected, with Leptoneta cornea Tong & Li, 2008 as the type species. Twenty-two Chinese species previously assigned to the genus Leptoneta Simon, 1872 are revised, with eight transferred to Falcileptoneta Komatsu, 1970 , seven transferred to Jingneta gen. nov ., five transferred to Leptonetela Kratochvil, 1978, and one species each transferred to Longileptoneta Seo, 2015 and Masirana Kishida, 1942. Eight new species are described: i.e., Falcileptoneta shuanglong Wang & Li sp. nov . (♂), Jingneta caoxian Wang & Li sp. nov . (♂♀), J. jingdong Wang & Li sp. nov . (♂♀), Longileptoneta gutan Wang & Li sp. nov . (♂♀), L. huangshan Wang & Li sp. nov . (♂♀), L. shenxian Wang & Li sp. nov . (♂♀), L. yeren Wang & Li sp. nov . (♂), and L. zhuxian Wang & Li sp. nov . (♂♀). In total, 127 leptonetid species from six genera are documented from China: nine species of Falcileptoneta, nine species of Jingneta gen. nov ., 101 species of Leptonetela, six species of Longileptoneta, one species of Masirana, and one species of Rhyssoleptoneta Tong & Li, 2007 .

In this work, we present the interaction solutions and abundant exact solutions for the new (3+1)-dimensional generalized Kadomtsev-Petviashvili equation based on the Hirota's bilinear form and a direct function. The obtained interaction solutions contain the interaction between the rational function and the $\tanh$ function and the interaction between the rational function and the $\cos$ function. The dynamical properties of these resulting solutions are analyzed and shown in three-dimensional plots, corresponding contour graphs and plane figures.

Herein, a (3+1)-dimensional generalized shallow water wave equation with variable coefficients is studied, which describes the flow below a pressure surface in a fluid. Abundant breather wave solutions are constructed via the Hirota bilinear form and a novel test function. Velocity, amplitude and shape changes of the breather wave solutions are shown in some 3D-graphs and contour plots by selecting different values of the variable coefficients. The novel test function is very effective for obtaining the breather wave solutions of the variable-coefficient nonlinear partial differential equations.

Under investigation is a generalized (3 + 1)-dimensional B-type Kadomtsev-Petviashvili equation with variable coefficients in fluid dynamics. Based on the Hirota's bilinear form and the positive quadratic function, abundant lump solutions are obtained.The interaction solutions between lump solutions and other solitons are also presented. Their dynamical behaviors are graphically shown with different choices of the free parameters., 11 pages, 44 figures, Current Status is "published" in "Journal of Mathematical Analysis and Applications" (2021)

Background: Shoulder joint pain is commonly seen in primary care. Were many of them diagnosed with rotator cuff disease especially involvement of supraspinatus tendon of rotator cuff. The progression of disease leads to tear of rotator cuff and the etiology is multifactorial. However, characteristic changes of acromion morphology appear as major risk factor for rotator cuff tear. According to an ancient classification of acromion type I (flat), type II (curved), or type III (hooked) introduced by Bigliani et al. also documented that incident of rotator cuff tear highly increased with type III (hooked) acromion. Continue study over acromion shape a rare new type IV (convex) acromion also discovered. Many studies have attempted to correlate acromion characteristic with rotator cuff tears. But result still we attempted to determine the rotator cuff tear in association with different shape of acromion through a systemic review of appropriate studies. Methods: Pubmed, Scopus and Baidu scholar database engine searched, limiting results to those published in the English language without limiting year. The key search terms utilized were “acromion morphology”/”rotator cuff tear” and “shoulder joint” / “impingement syndrome”. Over 150 abstract reviewed and 20 literatures were analyzed for quality and relevance study. Conclusions: On the base of previous published article, the different types of acromion shape distribution is not equally seen in population. The most common type II acromion appears large in number with or without rotator cuff disease. Those with type III acromion more than 70% found with degenerative changes or tear of rotator cuff. Current evidence suggests that pathological changes or tear of rotator cuff arise from a multivariare etiology. It increasingly evident that type III acromion plays greater role to rotator cuff tear than other type I and type II of Bilgiani acromion classification.

In this paper, a generalized (3 + 1)-dimensional variable-coefficient nonlinear-wave equation is studied in liquid with gas bubbles. Based on the Hirota's bilinear form and symbolic computation, lump and interaction solutions between lump and solitary wave are obtained. Their interaction phenomena is shown in some 3d graphs and contour plots, which include a periodic-shape lump solution, a parabolic-shape lump solution, a cubic-shape lump solution,interaction solutions between lump and one solitary wave, and between lump and two solitary waves. The spatial structures called the bright lump wave and the bright-dark lump wave are discussed. Interaction behaviors of two bright-dark lump waves and a periodic-shape bright lump wave are also presented., 16 pages, 70 figures

To determine the associations among diabetes status, Metformin administration and prostate cancer (PCa) detection at biopsy in Chinese population.A case-control study was conducted among a prospectively enrolled prostate biopsy cohort of 518 patients from Jan 2013 to Dec 2014 at our institute. Diabetes status and Metformin administration were determined through medical records and self-report. Different clinical characteristics were registered and compared among different groups. Univariate and multivariate logistic regression analyses were performed to evaluate the effects of diabetes status and Metformin administration on the detection of overall as well as high-grade PCa at biopsy.PCa was detected in 229 (44.2%) men, and high-grade PCa (Gleason score ≥8) was detected in 65 (12.5%) men. Diabetes was observed in 96 men, and 28 of them were administered with Metformin. Both overall and high-grade cancer detection rates were significantly higher in diabetic patients (p0.001). In multivariate analysis, diabetes status was a risk factor for high-grade cancer detection (OR 7.699, 95%CI 3.483-17.020, p0.001), but not for total PCa detection (OR 1.774, 95%CI 0.831-3.787, p=0.138). Meanwhile, Metformin administration was proved to be a protective factor for high-grade disease (OR 0.420, 95%CI 0.201-0.879, p=0.021) in multivariate analysis, while no correlation was detected with overall cancer detection (OR 0.786, 95%CI 0.172-3.593, p=0.756).Diabetes status was positively associated with biopsy-mediated high-grade PCa detection in Chinese population, while the positive association would be partly compromised by Metformin administration.

In this paper, a variable-coefficient symbolic computation approach is proposed to solve the multiple rogue wave solutions of nonlinear equation with variable coefficients. As an application, a (2+1)-dimensional variable-coefficient Kadomtsev-Petviashvili equation is investigated. The multiple rogue wave solutions are obtained and their dynamics features are shown in some 3D and contour plots., Comment: 12 pages, 26 figures

// Meng-Bo Hu 1, * , Hua Xu 1, * , Ji-Meng Hu 1 , Wen-Hui Zhu 1 , Tian Yang, Hao-Wen Jiang 1 , Qiang Ding 1 1 Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China * These authors have contributed equally to this work Correspondence to: Hao-Wen Jiang, email: urology_jhw@163.com Qiang Ding, email: qiangd_urol@126.com Keywords: leptin, adiponectin, prostate cancer, genetic polymorphism, meta-analysis Received: July 15, 2016 Accepted: October 12, 2016 Published: October 19, 2016 ABSTRACT Leptin and adiponectin signaling was associated with development and progression of various cancers. The present study aimed to clarify the role of genetic variants in leptin, adiponectin and their receptors in prostate cancer. After comprehensive search and manuscript scanning, a total of 49 genetic variants were enrolled and examined for their relations to cancer risk and aggressiveness. In the meta-analysis, LEP rs7799039 (allele contrast: OR 1.133, 95%CI 1.024-1.254), ADIPOQ rs2241766 (allele contrast: OR 1.201, 95%CI 1.015-1.422) and ADIPOR1 rs10920531 (allele contrast: OR 1.184, 95%CI 1.075-1.305) variants were identified to be correlated with increased risk of prostate cancer. On the contrary, LEPR rs1137101 (allele contrast: OR 0.843, 95%CI 0.730-0.973) and ADIPOR1 rs2232853 (allele contrast: OR 0.638, 95%CI 0.535-0.760) variants were associated with decreased risk of prostate cancer. From the pooled-review, we additionally recognized eight variants associated with cancer risk and another eight variants associated with cancer aggressiveness, respectively. These observations indicated important roles of leptin, adiponectin and their receptors in the development and progression of prostate cancer. The identified polymorphisms might assist in developing better risk-assessment tools, as well as generating novel targeted therapies, especially for obese cancer patients with impaired leptin and adiponectin signaling.

Debris flow is one of the major secondary mountain hazards following the earthquake. This study explores the dynamic initiation mechanism of debris flows based on the strength reduction of soils through static and dynamic triaxial tests. A series of static and dynamic triaxial tests were conducted on samples in the lab. The samples were prepared according to different grain size distribution, degree of saturation and earthquake magnitudes. The relations of dynamic shear strength, degree of saturation, and number of cycles are summarized through analyzing experimental results. The findings show that the gravelly soil with a wide and continuous gradation has a critical degree of saturation of approximately 87%, above which debris flows will be triggered by rainfall, while the debris flow will be triggered at a critical degree of saturation of about 73% under the effect of rainfalland earthquake (M>6.5). Debris flow initiation is developed in the humidification process, and the earthquake provides energy for triggering debris flows. Debris flows are more likely to be triggered at the relatively low saturation under dynamic loading than under static loading. The resistance of debris flow triggering relies more on internal frication angle than soil cohesion under the effect of rainfall and earthquake. The conclusions provide an experimental analysis method for dynamic initiation mechanism of debris flows.

This paper aims to construct new mixed-type periodic and lump-type solutions via dependent variable transformation and Hirota’s bilinear form (general bilinear techniques). This study considers the (3 + 1)-dimensional generalized B-type Kadomtsev–Petviashvili equation, which describes the weakly dispersive waves in a homogeneous medium in fluid dynamics. The obtained solutions contain abundant physical structures. Consequently, the dynamical behaviors of these solutions are graphically discussed for different choices of the free parameters through 3D plots.

High-fat diet induced obesity was associated with more aggressive prostate cancer. Recent research has demonstrated that integrin-linked kinase (ILK), β-parvin and downstream cofilin 1 jointly affected cancer progression. Meanwhile, these proteins were also involved in energy metabolism. Therefore, the present study was conducted to investigate the potential function of ILK, β-parvin and cofilin 1 in the high-fat diet-induced progression of prostate cancer. Transgenic mice with prostate cancer were employed, fed with different diets and sacrificed at 20 and 28 weeks. Tumor differentiation, extracapsular extension and metastasis were compared between the groups. Expression levels of ILK, β-parvin and cofilin 1 in prostate were evaluated by immunohistochemical analysis and determined by an immunoreactivity score. Public databases were applied for analysis and validation. It was detected that high-fat diet feeding promoted cancer progression in transgenic mice with prostate cancer, with increased expressions of β-parvin (P=0.038) and cofilin 1 (P=0.018). Higher expressions of ILK, β-parvin and cofilin 1 were also associated with poorer cancer differentiation. Additionally, higher mRNA levels of CFL1 were correlated with a worse disease-free survival in patients of certain subgroups from The Cancer Genome Atlas database. Further studies were warranted in discussing the potential roles of ILK, β-parvin and cofilin 1 in high-fat diet feeding induced progression of prostate cancer.

Background. We aimed to examine whether proinflammatory cytokines participated in prostate cancer (PCa) development and progression promoted by high-fat diet (HFD).Methods. TRAMP (transgenic adenocarcinoma mouse prostate) mice were randomly divided into two groups: normal diet group and HFD group. Mortality rate and tumor formation rate were examined. TRAMP mice were sacrificed and sampled on the 20th, 24th, and 28th week, respectively. Levels of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, and TNF-α, were tested by FlowCytomix. Prostate tissue of TRAMP mice was used for histology study.Results. A total of 13 deaths of TRAMP mice were observed, among which 3 (8.33%) were from the normal diet group and 10 (27.78%) from the HFD group. The mortality rate of TRAMP mice from HFD group was significantly higher than that of normal diet group (P=0.032). Tumor formation rate at 20th week of age of HFD group was significantly higher than that of normal diet group (P=0.045). Proinflammatory cytokines levels, including IL-1α, IL-1β, IL-6, and TNF-α, were significantly higher in HFD TRAMP mice.Conclusions. HFD could promote TRAMP mouse PCa development and progression with elevated proinflammatory cytokines levels. Proinflammatory cytokines could contribute to PCa development and progression promoted by HFD.

High-fat diet (HFD) -induced obesity is associated with more aggressive and lethal prostate cancer (PCa) in males, although the exact underlying mechanisms remain unclear. In the present study, transgenic adenocarcinoma of mouse prostate (TRAMP) models fed on an HFD (40% fat) or a control diet (CD; 16% fat) were generated, and cancer differentiation, local invasion and metastasis were compared at 20, 24 and 28 weeks. Mouse sera from each group were collected, and adipokines and cytokines were measured using multiplex immunoassays. HFD-sera and CD-sera were additionally processed into conditioned media (2.5% mixed sera), and in vitro studies were conducted to determine the proliferation, migration and invasion of cancer cells when conditioned media were used for culture. In TRAMP mice, HFD feeding increased body weight and adipose tissue deposition, and promoted the progression of PCa, specifically with regard to poorer differentiation, increased local invasion and metastasis rate. Sera from HFD-fed TRAMP mice contained increased levels of leptin, and a time-dependent increasing trend in the levels of CC chemokine ligand (CCL)3, CCL4, CCL5 and CXC chemokine ligand (CXCL)10 was observed. However, no alterations were detected in the levels of adiponectin, interleukin (IL)-4, IL-5, IL-6, IL-12p70, interferon-γ, tumor necrosis factor-α, CCL2, CCL7, CCL11, CXCL1 and CXCL2. In vitro studies determined that HFD-sera-conditioned medium promoted proliferation, migration and invasion of DU145 cells, as compared with CD-sera-conditioned medium and serum-free medium. In conclusion, the results of the present study suggested that the circulating adipokine and cytokine alterations in response to excess adipose tissue deposition induced by HFD feeding contributed to PCa progression.

The aim of the present study was to explore the effects of human cartilage-derived morphogenetic protein-2 (hCDMP-2)-expressing canine myoblasts on the repair of meniscal fibrocartilage injury. Purified canine myoblasts were infected with lentiviruses carrying an empty vector or the hCDMP-2 gene. The following four experimental groups were established to study the in vivo meniscal repair in a canine model of meniscal injury: Group A, suture only; group B, suture with the addition of the recombinant hCDMP-2 on a polylactic acid/polyglycolic acid (PLA/PGA) scaffold; group C, a PLA/PGA scaffold with canine myoblasts carrying the empty vector; and group D, a PLA/PGA scaffold with canine myoblasts expressing hCDMP-2. Samples of the regenerated tissue were extracted at weeks 3, 8 and 12 post-repair and analyzed by morphological observation, immunohistochemistry (IHC) and quantitative analysis. At week 12 post-repair, the scaffold material had completely dissolved in the control groups and no changes were observed at the injured area, while regenerated tissue was observed in group D only. Hematoxylin and eosin and Safranin-O staining techniques further revealed cartilage lacunae and fibers present at the red-red zone of the repaired tissue, while cartilage lacunae without fibers were observed at the white-white zone in group D. In addition, IHC studies demonstrated that collagen I and II, and the S-100 protein were expressed at the red‑red and the white-white zones of the repaired tissue in group D. It was concluded that purified canine myoblasts expressing the hCDMP-2 gene were able to promote meniscal fibrocartilage healing by regenerating fibrocartilage-like tissue. The tissue in the red-red zone was regenerated more rapidly than that in the white-white zone. Further studies are required to identify the best way to combine hCDMP-2 growth factor with myoblasts for use in the clinic due to the limitations regarding the clinical use of lentiviral infections.

This study was designed to investigate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) in the reabsorption of neovessels in collagen gel cultures of rat and mouse aortic rings. Aortic angiogenesis was associated with collagen lysis and production of the matrix-degrading enzymes MMP-2, MMP-9, and membrane-type MMP (MT1-MMP, or MMP-14). Vascular growth and regression were not affected by disruption of MMP-2 or MMP-9. In addition, no effect on vascular regression was observed by blocking plasmin, a protease implicated in the activation of MMPs, with ε-aminocaproic acid or by adding plasminogen, which caused a modest increase in vascular proliferation. Conversely, angiogenesis was blocked and vessels stabilized by inhibiting MT1-MMP with neutralizing antibodies, TIMP-2, TIMP-3, or TIMP-4. TIMP-1, which blocks MMP-2 and MMP-9 but is a poor inhibitor of MT1-MMP, had no antiangiogenic effect. However, TIMP-1 prolonged the survival of neovessels following angiogenesis. Vascular regression was accelerated in aortic cultures from TIMP-1- and TIMP-2-deficient mice. The vascular survival effect of anti-MT1-MMP antibodies and TIMPs with MT1-MMP inhibitory activity was associated with complete inhibition of collagen lysis. In contrast, TIMP-1 had no anticollagenolytic effect. These results indicate that MT1-MMP plays a critical role not only in angiogenesis but also in vascular regression and demonstrate that TIMPs with anti-MT1-MMP activity have opposite effects on angiogenic outcomes depending on the stage of the angiogenic process. This study also suggests the existence of a TIMP-1-mediated alternate pathway of vascular survival that is unrelated to MT1-MMP inhibitory activity.

Matrix metalloproteinases (MMPs) have been implicated in the formation of microvessels during angiogenesis, but their role in vascular regression is poorly understood. The rat aorta model of angiogenesis was used to study the function of MMPs at different stages of the angiogenic process. Gelatin zymography and Western analysis demonstrated production of MMP-2 and MMP-9 by aortic outgrowths in serum-free collagen gel culture. MMP-2 was found in both culture medium and collagen gel, whereas MMP-9 was predominantly associated with the gel. MMP expression increased gradually during the angiogenic growth phase and stayed high when vessels regressed and collagen lysed around the aortic rings. The MMP inhibitors, batimastat and marimastat, blocked formation of microvessels when added to the culture medium at the beginning of the experiment. They, however, stabilized the microvessels and prevented vascular regression after the angiogenic growth phase. This effect was observed also under conditions of angiogenic stimulation by basic fibroblast growth factor. MMP inhibitor-mediated stabilization of microvessels was associated with inhibition of collagen lysis and accumulation of collagen fibrils in the subendothelial space. This study demonstrates that MMPs promote microvessel formation during the early stages of angiogenesis, but also contribute to the reabsorption of the neovasculature in the later stages of this process. The time-dependent divergent effects of MMPs on microvessel growth and survival may influence the in vivo activity of MMP inhibitors used to treat angiogenesis-dependent disorders.

Test soils were collected from debris flow source area in the Weijia groove, Beichuan county, Sichuan province. Indoor artificial rainfall model tank test has been designed; it can be used to simulate the process of debris flow initiation for slope loose soil under the rainfall action. The debris flow starting condition and confluence process have been measured in this test, through the analyzing the relationship of the rainfall intensity, duration time before the starting, and the total rainfall capacity at the starting moment, the relationship between the volume of production flow and the water to soil ratio in production flow. All these research results can be used to simulate debris flow initiation mechanism obtained from model test focused on the seepage-induced action and its influence factors.

Primary open angle glaucoma (POAG) is a common cause of irreversible blindness. The variable etiology of POAG poses significant challenges for treatment and rehabilitation. We analyzed a large POAG patient cohort during treatment to reveal possible causes of vision disorder, assess vision-related quality of life (VRQL), and to evaluate the efficacy of rehabilitative treatments.We analyzed the visional disturbances in 500 POAG patients (890 eyes) by regular ophthalmic examination and visual field examination using Humphrey 30° perimetry. Appropriate rehabilitative treatments for POAG were prescribed based on results of clinical examination and included correction of ametropia, health education, counseling, and the fitting of typoscopes. VRQL was assessed before and after treatment by a VRQL self-assessment questionnaire.Scores on the VRQL self-assessment were significantly lower compared to healthy controls. The primary cause of the vision disturbances was ametropia (97.99%), and 51.61% of the ametropia eyes had not received appropriate correction. The secondary causes of visual impairment were glaucomatous neurodegeneration (26.29%), complicated cataract, or other accompanying eye diseases. The causes of the clinical low vision (44 patients) were glaucomatous neurodegeneration (32 eyes), fundus diseases (23 eyes), keratopathy (11 eyes), and other eye diseases (10 eyes). The VRQL scores of patients improved significantly after rehabilitation and the correction of ametropia (P0.01). Twenty-five patients with low vision were provided with typoscopes, and 21 (84%) experienced significant functional recovery, while the remaining low vision patients could see letter lines two or more levels lower (smaller) on visual charts in a near vision test.Vision disorders in POAG patients are common and severe. Appropriate rehabilitation, especially the correction of ametropia, can significantly improve VRQL as revealed by the self-assessment of POAG patients.

Contrast-enhanced ultrasonography (CEUS) is an important technique for depiction and assessment of tumor vascularity. This study aimed to explore the relationship between the morphological characteristics of tumor microvessels and enhancement patterns on CEUS in hepatocellular carcinoma (HCC).Eighty patients with HCC underwent CEUS using SonoVue before hepatectomy. Contrast-enhanced ultrasonographic enhancement patterns and quantitative parameters were recorded. The tumor tissue sections were immunostained with human CD34 monoclonal antibody. The patients were classified into a point-line type group (n = 36) and a loop-strip type group (n = 44) according to microvessel morphology. The microvascular density (MVD) in the different types of microvessels was calculated. The relationship between enhancement patterns of HCC lesions and morphological characteristics of tumor microvessels was analyzed.The mean MVD in HCC was 22.4+/-3.5 per 0.2 mm2 in the point-line group, and 19.6+/-6.7 per 0.2 mm2 in the loop-strip group, and there was no significant difference between them (t = 0.948, P = 0.354). In the portal vein phase, hypoenhancement was significantly more frequent in HCC (X2 = 4.789, P = 0.029) in the loop-strip group (40/44, 90.9%) than in the point-line group (26/36, 72.2%). The time to hypo-enhancement in the loop-strip group (mean 64.84+/-26.16 seconds) was shorter than that in the point-line group (mean 78.39+/-28.72 seconds) (t = 2.247, P = 0.022). The time to hypo-enhancement was correlated with MVD in the loop-strip group (r = -0.648, P = 0.001).The enhancement patterns on CEUS are related to tumor microvascular morphology, and the type of microvascular morphology influences CEUS characterization. CEUS, an important noninvasive imaging technique, is used to evaluate microvascular morphology and angiogenesis, providing valuable information for antiangiogenic therapy in HCC.

To investigate the cell-killing effect of adenovirus-mediated TK-ganciclovir (GCV) gene therapy in combination with tumor necrosis factor-alpha (TNF-alpha) against murine bladder carcinoma cells in vitro.Murine bladder carcinoma MB49 cells were transfected with the adenoviral vector containing TK gene and green fluorescent protein (GFP) gene. The transfection efficiency was observed and the TK gene expression in the transfected cells was detected by RT-PCR. The survival rate of MB49 cells in response to TNF-alpha treatment and that of the TK gene-transfected cells after treatment with GCV and GCV+TNF-alpha were determined by MTT assay. The apoptosis of the cells after the treatments was analyzed by flow cytometry.In cells transfected with TK gene, the cell inhibition rate increased gradually with the increment of GCV and TNF-alpha concentration. GCV in combination with TNF-alpha resulted in significantly increased killing efficiency of the cells as compared with GCV or TNF-alpha treatment alone, and the effect of the combined treatment was enhanced as the TNF-alpha concentration increased. GCV treatment (50 microg/ml) alone produced a cell killing rate of (24.39-/+1.10)%, and when combined with 5 microg/ml TNF-alpha, the rate was increased to (40.05-/+0.97) %, and further to (65.47-/+0.67) % when TNF-alpha concentration increased to 20 microg/ml. Flow cytometry revealed obvious apoptosis of the cells 8 h after treatments with TK/GCV, TNF-alpha, or TK/GCV+TNF-alpha, and the combined treatment resulted in the highest cell apoptotic rate.TK/GCV in combination with TNF-alpha can enhance the effect of suicide gene therapy against murine bladder carcinoma cells and effectively induce apoptosis of the cells.

To evaluate the toxic effects of the CD-TK fusion gene systems against prostate carcinoma cell line RM-1 for assessing the value of suicidal gene therapy for prostate carcinoma.CD-TK fusion gene and green fluorescent protein (GFP) gene were transfected into RM-1 cells through adenovirus vectors. RT-PCR was used to demonstrate successful transfection and transcription of the suicidal genes. The toxic effects of 5-FC and GCV used alone or in combination on the transfected cells were observed by MTT assay, with the non-transfected RM-1 cells serving as control.Cytotoxic activity of CD/5-FC and TK/GCV systems against RM-1 cells was observed, and combined treatment with the two drugs resulted in significantly lowered survival of CD-TK-expressing cells (P0.05). After exposure to 5-FC and GCV for 72 h, the survival rate of the transfected cells decreased to 71.56% and 47.27%, respectively, and their combined use resulted in a survival rate as low as 18.46%.CD-TK fusion double suicidal gene system can produce significantly stronger toxic effect against RM-1 cells in vitro than either of suicidal genes.

To evaluate the lethal effect of adenovirus-mediated HSV-TK-ganciclovir (GCV) gene therapy in combination with hydroxycamptothecin (HCPT) on hunman bladder carcinoma cell line T-24 cells.Human bladder carcinoma cell line T-24 was transfected with adenovirus expression vector containing TK gene and green fluorescent protein (GFP) gene, and the transfection efficiency was observed and TK expression detected by PCR. After successful cell transfection indicated by GFP expression, GCV and hydroxycamptothecin are respectively added into the cell culture with normal T-24 cells serving as the blank control group. The growth inhibition rate of hunman bladder carcinoma cells in response to HCPT treatment for 72 h and the cell survival rate of 24 h, 48 h and 72 h after transfection with different protocols were observed by MTT assay. The apoptosis of the cells treated with GCV (0.5 mg/ml)+HCPT (10 mg/L) for 4 h was observed by flow cytometry.The cell inhibition rate increased gradually with increment of HCPT concentration, from 14% at HCPT concentration of 0.01 mg/L to 60% at 50 mg/L, but for a concentration above 100 mg/L, the inhibition rate did not exhibit further increase (P=0.216). GCV alone and GCV in combination with HCPT both resulted in significantly decreased survival rate of human bladder carcinoma cells (P=0.00), and the killing efficiency of the cells by GCV+HCPT protocol increased obviously with increment of HCPT concentration and prolongation of the action time. The cells treated with 0.5 mg/ml GCV alone for 72 h retained a cell survival rate of 34.6%, which was lowered to only 8.07% with combined treatment with GCV (0.5mg/ml) and HCPT (10 mg/L). Typical apoptotic peak before M1 phase of the cells appeared 4 h after treatment with GCV+10 mg/ml HCPT, which resulted in a apoptosis rate of 52.93%.HSV-TK/GCV in combination with HCPT can enhance the lethal effect of suicide gene therapy against human bladder carcinoma cells and effectively induce apoptosis of the cells.

To evaluate the effect of combined use of oncolytic virus and the chemotherapeutic agents mitomycin (MMC) in growth inhibition of human bladder cancer cell line T-24 in vitro.Human bladder cancer cell line T-24 was infected with oncolytic virus (ONYX-015) of different multiplicity of infection, or treated with MMC in addition to ONYX-015. The changes in the cell growth, morphology, and apoptosis of cultured T-24 cells were observed by means of cell counting and fluorescence microscopy after the treatments. The effects of the treatment protocols were also tested in nude mouse model of implanted subcutaneous tumor.Combined use of ONYX-015 and MMC produced substantially stronger cytotoxic effect against T-24 cells than exclusive use of ONYX-015. In in vivo experiments, combination of oncolytic virus and MMC resulted in much more significant tumor growth inhibition than either of the agents used alone. Obvious T-24 cell apoptosis could be observed in response to combined ONYX-105 and MMC treatment and exclusive ONYX-105 treatment.ONYX-015 combined with MMC can produce significant cytotoxicity against T-24 cells and enhance therapeutic efficacy against bladder carcinoma.

To detect the expression of apoptosis gene PDCD5 in tissues of normal human kidney, renal clear cell carcinoma, normal bladder and bladder carcinoma, and explore the role of PDCD5 gene in renal clear cell carcinoma and bladder carcinoma.Indirect immunohistochemistry was employed to detect PDCD5 expression in 63 kidney specimens and 42 bladder specimens. Positive expression rates and intensity of PDCD5 protein expression in the kidney tissue were investigated microscopically and by computerized image analysis. Positive expression rate in the bladder tissue was investigated by microscopic observation.The results of immunohistochemical staining showed PDCD5 protein overexpression in the renal tubule of normal human kidney tissues and downregulation with the stage increase of renal clear cell carcinoma. PDCD5 protein expression showed statistical significance in tissues of normal kidney and renal clear cell carcinoma in all stages. No obvious PDCD5 expression was detected in the tissues of normal human bladder and bladder carcinoma.PDCD5 is an important apoptosis-regulating factor in the occurrence of renal clear cell carcinoma, and its expression is extremely low in tissues of normal human bladder and bladder carcinoma.

To evaluate the feasibility and efficacy of cytocine deaminase-thymidine kinase (CD-TK) fusion double suicide gene therapy using adenovirus mediated CD-TK gene and green fluorescent rotein (GFP) gene combined with ganciclovir(GCV) or 5-flourocytosine(5-FC) in a murine subcutaneous bladder carcinoma model.A replication defective adenovirus vector containing CD-TK gene was used. Subcutaneous tumors were established in syngenic C57BL/6 female mice with 1 x 10(6) Mb49 cells. Intratumoral injection of AdCD-TK (1.58 x 10(8) PFU, qd x days) in combination with GCV (40 mg.kg(-1).d(-1), ip, qd x 10 days) or 5-FC (400 mg.kg(-1).d(-1), ip, qd x 10 days) was administered in vivo for the determination of treatment efficacy in separate controlled experiments.In vivo experiments demonstrated that the mean volume of tumor in the group of AdCD-TK/GCV(326.58+/-109.56 mm(3)), AdCD-TK/5-FC (235.33+/-62.94 mm(3)) and AdCD-TK/(GCV+5-FC) (23.58+/-6.78 mm(3)) was reduced significantly compared with that of control group (993.51+/-158.32 mm(3)) (P=0.00), the mean volume of tumor in the group of AdCD-TK/(GCV+5-FC) was significantly less than that in the group of AdCD-TK/GCV or AdCD-TK/5-FC (P=0.04). Tumor necrosis was revealed by histomorphology compared with control animals.Adenovirus mediated CD-TK double suicide gene combining with GCV or 5-FC could provide an effective therapy in an experimental murine bladder carcinoma by significantly inhibiting tumor growth. The treatment efficacy of AdCD-TK combining GCV and 5-FC was superior to that of AdCD-TK combining GCV or AdCD-TK combining 5-FC.

Recent studies have implicated the Tie2 tyrosine-kinase receptor and its main ligands - angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) - as crucial regulators of mural cell recruitment during angiogenesis. Angiopoietin-mediated activation of Tie2 promotes perivascular mural cell assembly, but the mechanisms regulating this process are poorly understood because differentiated mural cells do not have the Tie2 receptor, which is reportedly expressed only in endothelial cells. There is also no direct evidence that Tie2 activation results in production of mural cell chemoattractants by the endothelium. In the rat aorta model of angiogenesis,developing microvessels recruit mural cells from the intimal/subintimal layers of the aortic wall. Ang-1 and Ang-2 promote angiogenesis in this system,stimulating branching morphogenesis and mural cell assembly. Mural precursor cells (MPCs) isolated with a nonenzymatic method from the intimal aspect of the rat aorta were positive for smooth muscle cell markers (α-smooth muscle actin and calponin) and negative for endothelial markers(factor-VIII-related antigen and CD31). These cells responded chemotactically to Ang-1 and Ang-2, and secreted MMP-2 when treated with these factors. Western-blot analysis, immunocytochemistry and RT-PCR demonstrated that MPCs express the Tie2 receptor. Immunoprecipitation showed phosphorylation of MPC Tie2 on tyrosine residues upon stimulation with Ang-1 or Ang-2. Surface expression of Tie2 was further demonstrated by isolating Tie2+/α-smooth muscle actin+ MPCs from primary aortic outgrowths with anti-Tie2-IgG-coated magnetic beads. Immunostaining of the rat aorta confirmed expression of Tie2 not only in endothelial cells but also in nonendothelial mesenchymal cells located in the aortic intimal/subintimal layers, which are the source of MPCs. These data indicate that the aortic wall contains Tie2+ nonendothelial mesenchymal cells and suggest that Tie2-related recruitment of mural cells during angiogenesis may occur through angiopoietin-mediated direct stimulation of these cells.

The roles of Na+/H+ antiport and intracellular pH in apoptosis of HL-60 cells were investigated here. We found that dimethyl amiloride, a specific Na+/H+ antiport inhibitor, induced intracellular acidification but not apoptosis; while sodium ionophore, monensin caused intracellular alkalinization as well as apoptosis in HL-60 cells. Br-A23187 and thapsigargin could induce a various degree of intracellular alkalinization through the stimulation of Na+/H+ antiport. Dimethyl amiloride blocked the intracellular alkalinization and inhibited apoptosis induced by Br-A23187 and thapsigargin. PMA also stimulated Na+/H+ antiport and induced intracellular alkalinization which was completely blocked by dimethyl amiloride and partially attenuated by PKC inhibitors. PMA could inhibit apoptosis in HL-60 cells. PMA-induced suppression of apoptosis was, however, not interfered by dimethyl amiloride, but could be abolished by PKC inhibitors. These results indicate that pHi alkalinization and/or the stimulation of Na+/H+ antiport, instead of intracellular acidification, are contributory to the induction of apoptosis. PMA-induced inhibition of apoptosis is not necessarily associated with intracellular alkalinization, but primarily due to activation of PKC. We suggest that stimulation of Na+/H+ antiport and pHi alkalinization act as facilitating factors in the induction of apoptosis.

In order to resolve the question whether or not transferrin could have a growth-promoting effect on cells independent of its action in iron transport, we investigated the effect of the iron-free form of transferrin, apotransferrin on cell activation and proliferation in the human leukemic HL60 cell line. Within a minute of its addition to HL60 cells, apotransferrin caused a rise in intracellular free calcium concentration ([Ca2+]i) in a dose-dependent manner and the higher the apotransferrin, the quicker it was to attain the calcium peak, showing the physiological characteristics of an agonist-induced [Ca2+]i elevation. The source of calcium appears to be extracellular since this signal could be abolished by nickel or when the reaction was carried out in calcium-free medium. Addition of apotransferrin in the serum-free medium could markedly promote DNA synthesis whereas addition of iron citrate could not. However, apotransferrin could not sustain cell proliferation and hypertrophism without other growth or nutritional factors. Antitransferrin receptor antibody inhibited the growth of HL60 cells cultured in serum-free medium supplemented with transferrin and insulin in a dose-dependent manner, whereas addition of ferric citrate could not reverse cell growth. Generation of the calcium signal probably reflects the initiation of the cell activation processes which could culminate into mitogenesis. Hence, our results suggest that apotransferrin, not iron, is bioactive in HL60 cells.

Background The aim of the study is to investigate whether body mass index (BMI) affected pathological characteristics and biochemical recurrence (BCR) of prostate cancer after radical prostatectomy in Chinese men. Methods Medical records of 211 Chinese patients who underwent radical prostatectomy between 2006 and 2014 were retrospectively reviewed, with follow-up time of 24.5 ± 27.0 months. Multivariate logistic and Cox regression analyses were applied to address the impact of BMI on adverse pathological outcomes and BCR following prostatectomy. A meta-analysis of published studies from MEDLINE or EMBASE was conducted to determine the relationship between BMI and BCR following prostatectomy among Asian populations. Results Higher BMI was positively correlated with higher biopsy Gleason score (odds ratios (OR) 1.163, 95 % confidence interval (CI) 1.023–1.322, P = 0.021) and pathological Gleason score (OR 1.220, 95 % CI 1.056–1.410, P = 0.007) in multivariate analysis. BCR was detected in 48 patients (22.7 %). Multivariate Cox proportional hazards analysis revealed that higher BMI (hazard ratio (HR) 1.145, 95 % CI 1.029–1.273, P = 0.013) and prostate-specific antigen (HR 1.659, 95 % CI 1.102–2.497, P = 0.015) levels were independent predictors of BCR. The meta-analysis enrolled eight Asian studies of 4145 patients treated by radical prostatectomy. Based on random-effects approach, a 5 kg/m2 increase in BMI was correlated with 28 % higher risk of BCR (HR 1.22, 95 % CI 0.86–1.72) without statistical significance. Conclusions The present study suggested that higher BMI was an independent risk factor for a higher Gleason score, as well as an independent predictor of BCR after radical prostatectomy in Chinese patients. Meta-analysis of Asian studies also indicated that obese patients, although without statistical significance, might be more likely to suffer from BCR.

Background Neo-adjuvant hormone therapy (NHT) following radical prostatectomy (RP) or radiotherapy has been utilized in the multimodal approach to patients with intermediate- to high-risk prostate cancer (PCa). Herein, we performed a systematic review and meta-analysis of published randomized trials to evaluate the clinical efficacy of NHT. Methods Literatures were searched from PubMed, EMBASE, Web of Science, and Cochrane Library for comparing neo-adjuvant therapy group (NHT plus radiotherapy or radical prostatectomy) with traditional therapy (radiotherapy or prostatectomy) alone. Quality of the research was assessed on the basis of the Cochrane’s risk of bias of randomized controlled trial. Comparable information were obtained from eligible trials and assembled for meta-analysis up to 31 August 2014. RevMan 5.2 software was used for statistical analysis. Results Fifteen randomized controlled trials (RCTs) (total 5,194 patients) were included in this study. Meta-analysis showed there was a significant improvement in overall survival (OS) (Odds ratio (OR) = 1.51, 95% confidence interval (CI) 1.22 to 1.87, P = 0.0002), positive surgical margin (PSM) rate (OR = 0.30, 95% CI 0.24 to 0.38, P