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To analyze the clinicopathological features and prognostic factors of gastric neuroendocrine carcinoma(NEC) based on a multicenter database from five medical centers in Southern China.Clinical and pathological data of 1 183 gastroenteropancreatic neuroendocrine neoplasms patients between January 2006 and December 2015 from five centers were retrospectively analyzed. A total of 156 gastric NEC cases(13.2%) with complete follow-up information were screened and included in the study, wherein 73 cases from Sun Yat-sen University Cancer Center, 27 cases from Nanfang Hospital of Southern Medical University, 26 cases from The First Affiliated Hospital of Sun Yat-sen University, 15 cases from Guangdong General Hospital and 15 cases from Sun Yat-sen Memorial Hospital of Sun Yat-sen University. The overall survival rate was calculated by using Kaplan-Meier method. The prognostic factor was analyzed using the Cox proportional hazards model.In 156 NEC patients, the ratio of male to female was 3.9 vs 1.0, the median age was 61 years old, and the maximal tumor diameter was (4.5±2.3) cm. There were 12 case(7.7%) with functional tumors. At the initial diagnosis, there were 111 patients (71.2%) with regional lymph node metastases and 58 patients (37.2%) with distant metastases. One hundred and twenty-three patients (78.8%) underwent surgical treatment and 94 patients (60.3%) received systematic treatment. There were 31 patients(19.9%) in localized disease stage, 67 patients (42.9%) in regional disease stage and 58 patients(37.2%) in distant disease stage. The 5-year overall survival rate was 44.7%. Cox regression model showed that surgical treatment (HR=0.512, 95%CI:0.287 to 0.912, P=0.023) and clinical stage(HR=1.488, 95%CI:1.067 to 2.076, P=0.019) were independent prognostic factors. The 5-year overall survival rate of patients with and without surgical treatment were 54.6% and 10.9%(P=0.000). Meanwhile, the 5-year overall survival for localized, regional and distant disease stages were 66.1%, 56.1% and 21.1% respectively(P=0.000).Gastric neuroendocrine carcinoma is a group of rare tumors with strong invasiveness, high malignancy and poor prognosis. The gastric NEC patients can benefit from surgical treatment.

A parametric study of tuned mass dampers for a long span transmission tower-line system under wind loads is done in this paper. A three-dimensional finite element model of transmission tower-line system is established by SAP2000 software to numerically verify the effectiveness of the tuned mass damper device. The wind load time history is simulated based on Kaimal spectrum by the harmony superposition method. The equations of motion of a system with tuned mass damper under wind load excitation are proposed, and the schematic of tuned mass damper is introduced. The effects of mass ratio, frequency ratio, damping ratio, the change of the sag of transmission line, and the robustness of TMD are investigated, respectively. Results show that(1)the change of mass ratio has a greater effect on the vibration reduction ratio than those of frequency ratio and damping ratio, and the best vibration reduction ratio of TMD is not the frequency ratio of 1;(2)the sag-span ratio has an insignificant effect on the vibration reduction ratio of transmission tower when the change of sag-span ratio is not large; and(3)the effect of ice should be considered when the robustness study of TMD is carried out.

Dendritic cells (DCs) are specialized antigen-presenting cells that are uniquely capable of either inducing immune responses or maintaining a state of self-tolerance, depending on their stage of maturation. In the present study, we describe a way to interfere with DCs maturation. The compound butyrate can affect the differentiation of DCs generated from human monocytes and can inhibit T cell proliferation. We demonstrate that butyrate substantially down-regulates the expression of CD80, CD83, and MHC class II molecules; increases endocytic capability; reduces allostimulatory abilities; promote interleukin-10 (IL-10) production; and inhibits interleukin-12 (IL-12) and interferon-γ (IFN-γ) production. These results demonstrate a specific immune suppression property of butyrate and supports further investigation for butyrate as a new immunotherapeutic agent.

Our previous study revealed that neuroendocrine differentiation in colorectal cancer is one of the important factors leading to worse prognosis. In this study, we apply immunohistochemical staining, Western-blot, RT-PCR and ELISA to investigate the underlying mechanism that how the neuroendocrine differentiation to affect the prognosis of colorectal cancer. The interaction of colorectal cancer cells, neuroendocrine-like cells and tumor-associated macrophages in colorectal cancer progress is also investigated. By analyzing 82 cases of colorectal cancer patients treated in our institution, we found that colorectal adenocarcinoma with neuroendocrine differentiation had increasing number of tumor-associated macrophages and worse prognosis. Further evaluation of cytology showed that neuroendocrine cells have the ability to recruit tumor-associated macrophages to infiltrate the tumor tissue, and the tumor-associated macrophages enhance the proliferation and invasion abilities of the colon cancer cells. Moreover, we confirmed that CXCL10 and CXCL11 are the key chemokines in neuroendocrine-like cells and they promote the chemotaxis activity of tumor-associated macrophages. The secretion of CXCL10 and CXCL11 by neuroendocrine-like cells can recruit tumor-associated macrophages to infiltrate in tumor tissues. The latter enhances the proliferation and invasion of colorectal cancer cell and lead to poor prognosis.

The potential anti-neoplastic activity of terpenoids is of continued interest. In this study, we investigate whether methyl sartortuoate, a terpenoid isolated from soft coral, induced cell cycle arrest and apoptosis in a human colon cancer cell line. Culture studies found that methyl sartortuoate inhibited colon cancer cell (LoVo and RKO) growth and caused apoptotic death in a concentration- and time-dependent manner, by activation of caspase-8, caspase-9, caspase-3, p53 and Bax, and inactivation of B-cell lymphoma 2 (Bcl-2) apoptosis regulating proteins. Methyl sartortuoate treatment led to reduced expression of cdc2 and up-regulated p21 and p53, suggesting that Methyl sartortuoate induced G2-M arrest through modulation of p53/p21/cdc2 pathways. Methyl sartortuoate also up-regulated phospho-JNK and phospho-p38 expression levels. This resulted in cell cycle arrest at the G2-M phase and apoptosis in LoVo and RKO cells. Treatment with the JNK inhibitor SP600125 and the p38 MAPK inhibitor SB203580 prevented methyl sartortuoate-induced apoptosis in LoVo cells. Moreover, methyl sartortuoate also prevented neoplasm growth in NOD-SCID nude mice inoculated with LoVo cells. Taken together, these findings suggest that methyl sartortuoate is capable of leading to activation of caspase-8, -9, -3, increasing p53 and Bax/Bcl-2 ratio apoptosis through MAPK-dependent apoptosis and results in G2-M phase arrest in LoVo and RKO cells. Thus, methyl sartortuoate may be a promising anticancer candidate.

In this paper, we propose a method for detecting communities from signed social networks with both positive and negative weights by modeling the problem as a multi-objective problem. In the experiments, both real world and synthetic signed networks whose size ranges from 100 to 1200 nodes are used to validate the performance of the new algorithm. A comparison is also made between the new algorithm and an effective existing algorithm, namely FEC. The experimental results show that our algorithm obtains a good performance on both real world and synthetic data, and outperforms FEC clearly.

To investigate the level of Hs-CRP, Fib,IL-6, TNF-α,MDA, SOD, and analyse the correlation between the level of plasma inflammatory cytokines and clinical significance in patients with anterior ST-segment depression.We choose 360 patients with inferior ST Segment elevation acute myocardial infarction from May 2007 to Sep 2012 in rescue Center of Anzhen Hospital, in Anzhen Hospital, and all the patients received percutaneous coronary intervention treatment and the vascular lesions besides culprit vessel were observed. All the patients were divided into two groups: control group (n = 180) and anterior ST-segment depression group (n = 180). 8ml venous blood was obtained from all the patients, and then plasma were separated. The level of plasma Hs-CRP, Fib, IL-6, TNF-α, MDA, SOD were investigated by Biochemistry and ELISA. And the relativity between the level of plasma inflammatory cytokines and anterior ST-segment depression in patients with inferior acute myocardial infarction was analysed.The proportion of double vessel coronary disease, three coronary artery lesion is higher in anterior ST-segment depression group compared with control group (P0.01) . Compared with control group, the level of Hs-CRP, Fib, IL-6, TNF-α,MDA, SOD of anterior ST-segment depression group are inclined significantly (P0.01).The level of plasma inflammatory cytokines and the degree of lipid peroxidation can reflect the severity of coronary artery disease and may have certain value in predicting the severity of disease.

Background Tumor-associated macrophages (TAMs) are known to promote cancer progression and metastasis through the release of a variety of cytokines. Phosphatase of regenerating liver (PRL-3) has been considered as a marker of colorectal cancer (CRC) liver metastasis. Our previous research suggests that PRL-3 can enhance the metastasis of CRC through the up-regulation of intermediate-conductance Ca2+-activated K+ (KCNN4) channel, which is dependent on the autocrine secretion of tumor necrosis factor-alpha (TNF-α). However, whether TAMs participate in the progression and metastasis of CRC induced by PRL-3 remains unknown. Methods We used flow cytometry, coculture, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, and immunofluorescence staining to determine the effect of TAMs on the ability of PRL-3 to promote invasiveness of CRC cells. Results In this study, we found that TAMs facilitated the metastasis of CRC induced by PRL-3. When TAMs were cocultured with CRC cells, the expression of KCNN4 was increased in TAMs and the invasion of CRC cells was enhanced. Furthermore, cytokines that were secreted by TAMs, such as IL-6 and IL-8, were also significantly increased. This response was attenuated by treating TAMs with the KCNN4 channel-specific inhibitor, 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34), which suggested that KCNN4 channels may be involved in inducing the secretion of IL-6 and IL-8 by TAMs and improving CRC cell invasiveness. Moreover, the expression of KCNN4 channels in TAMs was regulated through the NF-κB signal pathway, which is activated by TNF-α from CRC cells. Immunofluorescence analysis of colorectal specimens indicated that IL-6 and IL-8 double positive cells in the stroma showed positive staining for the TAM marker CD68, suggesting that TAMs produce IL-6 and IL-8. Increased numbers of these cells correlated with higher clinical stage. Conclusions Our findings suggested that TAMs participate in the metastasis of CRC induced by PRL-3 through the TNF-α mediated secretion of IL-6 and IL-8 in a paracrine manner.

Background: The gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine neoplasm. We summarized data in our centre to investigate the clinicopathological features, diagnostic methods, therapeutic approaches and prognosis for this neoplasm to increase knowledge of this disease in Asian populations. Method: A total of 122 patients treated at Sun Yet-san Memorial Hospital of Sun Yat-sen University between January 2000 and December 2011 were analyzed retrospectively. Results: Pancreas was the most common site of involvement (65/122, 53.3%); this disease has no special symptoms; positive rates of chromogranin A (CgA) and synaptophysin (Syn) were 81.1% and 87.7%, respectively. The positive rate of Syn had statistical difference among the three grades, but not CgA. Some 68 patients had G1 tumors, 32 G2 tumors and 22 G3 tumors, and Chi-square test showed that higher grading was correlated with worse prognosis (χ 2 =32.825, P=0.0001). A total of 32 patients presented with distant metastasis, and 8 cases emerged during following up. Cox proportional hazards regression modeling showed that the tumor grade (P=0.01), lymphatic metastasis (P=0.025) and distant metastasis (P=0.031) were predictors of unfavorable prognosis. The overall 5-year survival rate was 39.6%, the 5-year survival rate of G1 was 55.7%, and the G2 and G3 were 34.2% and 0%, respectively.Conclusions: The incidence of gastroenteropancreatic neuroendocrine tumors has risen over the last 12 years. All grades of these diseases metastasize readily, and further research regarding the treatment of patients after radical surgery is needed to prolong disease-free survival.

Aims A retrospective, case–control study to investigate the J wave, a J-point elevation on resting 12-lead electrocardiograms, as a risk factor for sudden cardiac arrest (SCA) in patients diagnosed with hypertrophic cardiomyopathy (HCM). Methods Patients with HCM and age- and sex-matched healthy control subjects were recruited, and 12-lead electrocardiograms were performed. The prevalence and related characteristics of J waves were assessed. Patients were followed-up for a mean of 47.9 months. Results Patients with HCM ( n = 345) had significantly higher prevalence of J waves than healthy controls ( n = 690; 11.6% and 7.1%, respectively). During follow-up, 14 patients with HCM experienced SCA (SCA subgroup). The prevalence of J waves was significantly higher in the SCA subgroup than in the non-SCA subgroup (42.9% and 10.3%, respectively). There were no significant differences between the SCA and non-SCA subgroups in J wave morphology. Conclusion The J wave may be a risk factor for SCA in patients with HCM.

Studies have shown that phosphatase of regenerating liver-3 (PRL-3) promotes the invasion, migration, and metastasis of human tumor cells by facilitating an epithelial–mesenchymal transition (EMT). However, the mechanism by which PRL-3 induces tumor cell EMT is unknown. Our previous research revealed that PRL-3 promotes LoVo cell proliferation by up-regulating KCNN4 channels. In the current study, we explored the mechanism by which PRL-3 mediates EMT. We demonstrated that PRL-3 induced the expression of KCNN4 channels, leading to EMT and the down-regulation of E-cadherin. Further studies revealed that KCNN4 channels increased intracellular calcium levels and activated components of cell signaling downstream of calcium, including CaM-kinase II and glycogen synthase kinase-3 beta (GSK-3 beta), which increased Snail expression. Inhibiting KCNN4 with siRNA and TRAM-34, a specific inhibitor, restored E-cadherin expression and inhibited Snail expression. These results implicated the up-regulation of KCNN4 channels in the PRL-3-mediated induction of EMT and promotion of cancer metastasis.

Previous studies have shown that phosphatase of regenerating liver-3 (PRL-3) plays an important role in the metastasis and proliferation of tumor cells. However, the mechanism by which PRL-3 controls the cell cycle of tumor cells remains unknown. In the present study, considering that the K+ channels strictly control cell proliferation, we examined whether K+ channels participate in the proliferation of tumor cells induced by PRL-3. Interestingly, the expression of intermediate-conductance Ca2+-activated K+ channels (KCNN4) was upregulated in an NF-κB-dependent manner when PRL-3 was transfected into LoVo cells. Also, we identified two NF-κB binding sites in the promoter region of KCNN4. Use of the specific inhibitor 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) significantly inhibited the proliferation induced by PRL-3 and blocked the cell cycle at the G2/M phase. Meanwhile, the level of phosphorylation of Cdc2 was increased in a dose-dependent manner. Furthermore, TRAM-34 also inhibited tumor formation of PRL-3 cell xenografts implanted by injection in nude mice. In conclusion, PRL-3 promoted the proliferation of LoVo cells through upregulation of KCNN4 channels which facilitated the G2/M transition.

It is a challenging task to handle dense multipath environment in a wireless communication channel. Various techniques were suggested to handle this issue such as power control, antenna, time and frequency diversity etc. However, antenna diversity is considered to be the most practical way to handle multipath fading. In this paper, a deterministic UWB channel model was developed based on ray-tracing technique using the art of 3D computer game technology. Reflection, refraction and scattering phenomena were successfully implemented. The model was then enhanced to use multiple antennas on both sides of the system. Simulation results show great improvement in channel impulse response (CIR) in case of multiple antennas. Moreover, the frequency effect on channel impulse response was analyzed for 500 MHz–4 GHz range. Our results indicate that the change in frequency does not affect the channel behaviour a lot but changes the pattern of received rays.

One of the most challenging tasks in modeling a wireless channel is to handle time-varying multipath fading. There are various techniques to tackle this issue such as power control, antenna diversity etc. However, antenna diversity is more practical and effective technique to tackle dense multipath environment observed in Ultra Wide Band (UWB). In this paper, an efficient UWB channel modeling scheme is presented. First, the channel is simulated using single antenna on both sides of the system by taking into account both reflection and refraction of the transmitted ray. The dense multipath channel of UWB is then efficiently exploited by using different configuration of multiple antennas on both sides (transmit/receive sides). Simulation results show great improvement in channel impulse response (CIR) in case of multiple antennas. Moreover, this improvement in CIR is monotonically gradual in the sense that the CIR becomes denser upon increasing number of antennas on both sides of the system. The modelling scheme is based on ray tracing algorithm that has been developed using the art of computer game technology.