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In this paper, a disturbance observer-based complementary fractional-order sliding mode control (CFOSMC) scheme is proposed for the permanent magnet synchronous motor (PMSM) drive system. First, to reconstruct the load disturbance and parameter variations, a nonlinear disturbance observer is designed. Next, a disturbance observer-based fractional-order sliding mode with a saturation function control law is designed to reduce the chattering problem in the existing fractional-order sliding mode control (FOSMC) method. Furthermore, to reduce the thickness of the boundary layer, a CFOSMC scheme is designed. By using the fractional-order Lyapunov stability theorem, the existence condition and the chattering problem are analyzed. Compared with the existing FOSMC, the obtained CFOSMC law does not contain any high-order derivatives of tracking error, which is easier to implement. Finally, the numerical simulations and experimental results are provided to show the superiority of the proposed method. To improve the performance of the permanent magnet synchronous motor (PMSM) drive system in terms of tracking rapidity, accuracy, and robustness, a complementary fractional-order sliding mode control (CFOSMC) scheme with disturbance observer is proposed in this paper.

Background Pancreatic cancer is one of the most malignant tumors, and gemcitabine has been considered as the standard treatment and been widely utilized as a first-line drug for advanced pancreatic cancer, but gemcitabine-resistance always occurs after a short period of treatment. Methods Two pancreatic cancer cell lines Panc-1 and MIA-PaCa-2 were used as the study subject and their gemcitabine-resistant cells were established. Both drug-resistant cells were divided into four groups: blank, emodin, gemcitabine, and emodin+gemcitabine. Cell viability was detected by MTT assay. Flow cytometry was performed to detect cell apoptosis rate and P-gp function. Quantitative real-time polymerase chain reaction and Western blotting were used to detect Survivin, XIAP, Caspase-9/3, NF-κB p65, IKKβ and IκB-α mRNA/protein expressions, respectively. Electrophoretic mobility shift assay (EMSA) was performed to detect NF-κB binding activity. Rhodamine 123 efflux assay was used to detect P-gp function. Results Emodin could inhibit cell activity in all cell lines. Both emodin and gemcitabine can significantly increase the apoptosis rate, and the combination of the two drugs can further significantly increase the apoptosis rate in normal pancreatic cancer cell lines. In both drug-resistant pancreatic cancer cell lines, it can be observed that although gemcitabine can increase the apoptosis rate, the effect of promoting apoptosis is significantly lower than that of emodin; the drug combination can still significantly increase the apoptosis rate on the basis of emodin alone. Emodin can significantly reduce the mRNA and protein expression levels of Survivin, XIAP, NF-κB, and IKKβ, and significantly increase the mRNA and protein expression levels of Caspase-3/9 and IκB-α. Emodin significantly reduced NF-κB activity and emodin significantly promoted P-gp fluorescence intensity from Rhodamine 123 efflux assay. Conclusion Emodin inhibits the expression of IKKβ, thereby inhibiting the expression and activity of downstream NF-κB, and inhibits P-gp function at the same time, ultimately achieving the purpose of reversing the drug-resistance of pancreatic cancer cell lines.

This paper concerns the design problem of optimal preview repetitive control (OPRC) for impulse-free continuous-time descriptor systems. First, by using a linear transformation, the descriptor system is transformed into a normal system with relatively low dimensionality and an algebraic system. Based on this, an augmented system which contains the error vector and the derivative of the normal system is constructed. Then, applying the lift technique and introducing a new performance index, the OPRC designing problem is converted into a regulation problem. Based on the optimal control theory, the regulator problem of the augmented system is solved. Furthermore, the explicit OPRC law for the original system is deduced. Different from the existing results, the preview feed-forward and error integral compensations are added into the OPRC system, which can significantly improve the tracking performance. Finally, a numerical example simulation result verifies the validity of the proposed method.

PurposeThe popularization of the internet has promoted the implementation of China's national fitness strategy and created conditions for Chinese residents to participate in sports. The internet is an essential medium for disseminating sports knowledge, and the use of the internet can change sport participation behaviors. Therefore, the internet can be used to popularize sports knowledge and promote the participation of all people in sports and thus improve the health of the entire population. This study attempts to empirically analyse how the use of the internet changes sport participation behavior.MethodUtilizing data from the 2017 China General Social Survey, a probit model, ivprobit model, and bias-corrected non-parametric percentile bootstrap test were used to analyse the impact of internet use on sport participation behavior.ResultsThe empirical results show that internet use significantly increased the probability of participation in sports by Chinese residents. Heterogeneity test results showed that internet use was more effective in promoting sport participation in middle-aged groups, groups of older persons, unmarried groups, and groups with a high school education or above. The mediating effect test results showed that internet use influenced residents' participation in sports by promoting social interaction, leisure and entertainment, and learning and recharging.ConclusionsThe internet has changed participation in sports; specifically, the use of the internet promotes sport participation. Additionally, internet use has a more obvious impact on improving the sport participation behavior of middle-aged, older, unmarried, and middle- and higher-educated individuals. Internet social interaction, internet entertainment and internet learning are effective channels to encourage Chinese residents to participate in sports and improve their health.

Background Aberrant endocytic recycling has fundamental functions on plasma membrane component turnover. Recent studies have identified an uncharacterized protein, CCDC132, in the endosome-associated recycling protein complex. Besides, our preliminary data first showed that CCDC132 was elevated in malignant neoplasms, especially in esophagus/stomach cancers. However, the functions and the underlying mechanisms of CCDC132 in gastric cancer (GC) biology remain unclear. Methods The CCDC132 mRNA expression in 4 GC cell lines and normal gastric epithelial cell lines was detected by qRT-PCR. Then, CCDC132 was downregulated in AGS and MGC-803 cells by lentivirus-induced RNA interfere, and cell viability assay, clone formation assay and apoptosis assay were carried out. The mechanism of CCDC132 on cell proliferation and apoptosis activation was explored using PathScan® Stress, apoptosis signaling arrays and Western blot. We further investigated the pro-oncogenesis of CCDC132 in vivo. Meanwhile, immunohistochemistry was utilized to analyze the association between CCDC132 expression and clinicopathological features and prognosis. Finally, the correlation between CCDC132 and p53 was analyzed by Spearman's rank correlation analysis. Results In this study, knockdown of CCDC132 significantly decreased cell proliferation and clone formation ability and facilitated apoptosis, and increased phosphorylation of p53 and Chk2 and protein levels of γ-H2AX, 53BP1, cleaved Caspase 3 and cleaved PARP. Additionally, knockdown of CCDC132 attenuated tumorigenesis and tumor growth of MGC-803 cell xenografts. CCDC132 expression was significantly higher in GC tissues compared with that in adjacent normal tissues and was positively correlated with nodal metastasis and TNM stage and negatively associated with prognosis. The survival rate of CCDC132 positive patients was lower than that of CCDC132-negative patients. Furthermore, CCDC132 expression was negatively related to p53. Conclusion This study unravels that knockdown of CCDC132 attenuates GC cell proliferation and tumorigenesis by facilitating DNA damage signaling, indicating that CCDC132 may serve as a potential target for GC therapy.

Background Excessive expression of EGFR is closely related to tumor formation, transfer and deterioration, which has attracted much attention. EGFR overexpression may be detected in up to 90% of pancreatic tumors. However, drug resistance of EGFR inhibitors targeting treatment severely limits its clinical application. Methods In this study, Western blotting was used to detect the expression of p-Stat3, EGFR, Bcl-2, cleaved-caspase3 and Bax. Cell apoptosis was evaluated via flow cytometry. The colon assay and MTT assay were applied for detecting the cell proliferation in vitro. The xenograft mouse model was used to examine the cell proliferation in vivo. Results Emodin remarkably enhanced the anti-cancer effect of EGFR inhibitor on pancreatic cancer cells. In addition, emodin promoted afatinib-induced apoptosis by inhibiting the Stat3 signaling pathway. Meanwhile, siRNAs against Stat3 significantly increased the apoptosis of pancreatic cancer cells. EGFR inhibitor promoted phosphorylation of Stat3 in pancreatic cancer cells. Interestingly, emodin combined with EGFR inhibitor inhibited the proliferation of pancreatic cancer cells in vitro. The tumor xenograft mice model was further confirmed that emodin possessed a synergy anticancer effect with afatinib on pancreatic cancer cells by regulating the Stat3 expression. Conclusion These results indicate that the combination of emodin with EGFR inhibitor is an effective therapeutic strategy to sensitize human pancreatic cancer.

Background Hepatocellular carcinoma (HCC) is the second leading cause of death among cancers worldwide. In this study, we aimed to identify the molecular target genes and detect the key mechanisms of HCC. Three gene expression profiles (GSE84006, GSE14323, GSE14811) and two miRNA expression profiles (GSE40744, GSE36915) were analyzed to determine the molecular target genes, microRNAs (miRNAs) and the potential molecular mechanisms in HCC. Methods All profiles were extracted from the Gene Expression Omnibus database. The identification of the differentially expressed genes (DEGs) was analyzed by the GEO2R method. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) enrichment analysis performed database for Integrated Discovery, Visualization and Annotation. The miRNA-gene network and protein-protein interaction (PPI) network were correlated by the Cytoscape software. The key target genes were identified by the CytoHubba plugin, Molecular Complex Detection (MCODE) plugin and miRNA-gene network. The identified hub genes were testified for survival curve using the Kaplan-Meier plotter database. Results Expression profiles had 592 overlapped DEGs. The majority of the DEGs were enriched in membrane-bounded organelles and intracellular membrane-bounded organelles. These DEGs were significantly enriched in metabolic, protein processing in the endoplasmic reticulum and thyroid cancer pathways. PPI network analysis showed these genes were mostly involved in the pathogenic Escherichia coli infection and the regulation of actin cytoskeleton pathways. Combining these results, we identified 10 key genes involving in the progression of HCC. Finally, PLK1, PRCC, PRPF4 and PSMA7 exhibited higher expression levels in HCC patients with poor prognosis than those for lower expression via Kaplan-Meier plotter database. Conclusion PLK1, PRCC, PRPF4 and PSMA7 could be potential biomarkers or therapeutic targets for HCC. Meanwhile, the metabolic pathway, protein processing in the endoplasmic reticulum and the thyroid cancer pathway may play vital roles in the progression of HCC.

This paper concerns a Padé-approximation-based preview repetitive control (PRC) scheme for continuous-time linear systems. Firstly, the state space representation of the repetitive controller is transformed into a nondelayed one by Padé approximation. Then, an augmented dynamic system is constructed by using the nominal state equation with the error system and the state equation of a repetitive controller. Next, by using optimal control theory, a Padé-approximation-based PRC law is obtained. It consists of state feedback, error integral compensation, output integral of repetitive controller, and preview compensation. Finally, the effectiveness of the method is verified by a numerical simulation.

In this paper, we present an optimal H2 model reduction method on the basis of the trust-region technique for linear time-invariant discrete-time dynamical systems. First, based on the poles and re...

Aims In order to explore the etiology of gastric cancer on global gene expression level, we developed advanced bioinformatic analysis to investigate the variations of global gene expression and the interactions among them. Main methods We downloaded the dataset GSE63288 from Gene Expression Omnibus (GEO) database which included 22 human gastric cancer and 22 healthy control samples. We identified the differential expression genes, and explored the Gene ontology (GO) and pathways of the differentially expressed genes. Furthermore, integrative interaction network and co-expression network were employed to identify the key genes which may contribute to gastric cancer progression. Key findings The results indicated that 5 kinases including BUB1, TTK protein kinase, Citron Rho-interacting kinase (CIT), ZAK and NEK2 were upregulated in gastric cancer. Interestingly, BUB1, TTK, CIT and NEK2 have shown high expression similarities and bound with each other, and participated in multiple phases of mitosis. Moreover, a subnet of co-expression genes e.g. KIF14, PRC1, CENPF and CENPI was also involved in mitosis which was functionally coupled with the kinases above. By validation assays, the results indicated that CIT, PRC1, TTK and KIF14 were significantly upregulated in gastric cancer. Significance These evidences have suggested that aberrant expression of these genes may drive gastric cancer including progression, invasion and metastasis. Although the causal relationships between gastric cancer and the genes are still lacking, it was reasonable to take them as biomarkers for diagnosis of gastric cancer.

The effective antitumor drug evodiamine (EVO) is attracting increased attention. Therefore, the present study aimed to investigate the effects of EVO on the proliferation, apoptosis and autophagy of human pancreatic cancer (PC) cell lines in vitro and in vivo. Human PANC‑1 and SW1990 PC cell lines were treated with different concentrations of EVO and proliferation was detected using a Cell Counting Kit (CCK)‑8 assay. Colony formation and wound‑healing assays showed that EVO inhibited PC cell viability and migration, and apoptosis was detected using flow cytometry. Western blotting and immunofluorescence detected the expression of proteins in PANC‑1 and SW1990 cells. The PANC‑1 cells were used to establish an orthotopic pancreatic tumor model in nude mice. Tumor‑bearing nude mice were administered with different concentrations of EVO, and growth was monitored. High‑resolution positron emission tomography and fluorine‑18‑labeled fluorodeoxyglucose were used to monitor the tumor/non‑tumor (T/NT) ratio and standard uptake value (SUV) of the mice, which were subsequently sacrificed to measure the transplanted tumor weight. Apoptosis increased with increasing EVO concentration. The EVO‑treated PC cells exhibited significantly higher expression of LC3II than the controls cells. EVO decreased LC3II, enhanced P62 and inhibited the expression of Akt, extracellular‑signal‑regulated protein kinase (ERK)1/2 and p38. Compared with the control group, the T/NT ratio, SUV and tumor weight decreased more markedly in the EVO‑treated group. The tumor expression of phosphorylated AKT, detected using immunohistochemistry, decreased with increasing EVO doses in vivo. EVO induced PC cell apoptosis by inhibiting phosphoinositide 3‑kinase/AKT and mitogen‑activated protein kinase/ERK and inhibiting the phosphorylation of signal transducer and activator of transcription activator 3 in PC cells to inhibit autophagy, suggesting that EVO may be considered as a novel PC treatment.

Because college outdoor sports clubs still have a series of problems, especially in terms of risk aversion measures, this paper classifies the risks of college outdoor sports clubs from six aspects, include decision risk, guide risk, student participant risk, equipment risk, environmental risk, school and parental risk. Finally, based on these six risks, reasonable suggestions were put forward for the risk management of college outdoor sports clubs.

With the rapid development of the global sports industry and the rapid promotion of the global economy, sports marketing brings more and more considerable benefits to the event enterprises. And sports communication plays an increasingly obvious role in expanding the influence of large-scale events. More and more large-scale sports events, including the Olympic Games, seek to maximize the comprehensive benefits through a combination of these two methods by sports marketing communication. From the perspective of cultural marketing, this paper analyzes the characteristics and interactive relations of the five main bodies of sports marketing communication—sports organizations, media, sponsors, audiences/consumers and intermediary companies, and explores the sports marketing communication mode of the 2022 Beijing winter Olympic Games.

Genomic DNA was extracted from 1 038 peripheral blood samples from HIV-infected individuals in Henan Province. One-step single-tube nested PCR was performed to amplify the 529 bp repeating sequences of Toxoplasma gondii. Of the 1 038 samples （762 from males and 276 from females）, 66 showed positive PCR results, with a positive rate of 6.4%. The PCR positive rate in males and females was 6.3% （48/762） and 6.5% （18/276） respectively. The PCR positive rate in the married HIV individuals was 4.9%（25/508）, and that in unmarried, divorced and widowed HIV individuals was 7.7% （41/530）（χ2 = 3.451, P0.05）. The PCR positive rate in HIV individuals with a high-school educational level or above was 6.9%（34/489）, and that in those below the high-school level was 5.8% （32/549）（χ2 = 0.545, P0.05）. The highest infection rate was in the age group of 20-40 years（7.6%, 31/410）. In addition, the Toxoplasma infection rate in those with and without a history of venereal diseases, and those with an unknown history was 8.0%（9/113）, 6.5%（50/773） and 4.6%（7/152） respectively （χ2 = 0.355, P0.05）.

Pentamode metamaterial (PM) is a kind of artificial microstructure extremum material with solid morphology and fluid properties proposed by Milton and Cherkaey. By decoupling the compression and the shear waves, the periodic structure is difficult to be compressed, but the shear deformation occurs easily. Theoretically, acoustic metamaterials consisting of such periodic arrangement of structural units can achieve complete matching with water. Therefore, the characteristics of adjustable modulus anisotropy, small stuffing rate and broadband endow the PMs with excellent acoustic control ability, which has attracted more attention of researchers. In this paper, the narrow-diameter intersection point P (0.25a, 0.25a, 0.25a) of an isotropic three-dimensional PM selected as the reference point in four different directions (X-axis, Y-axis, Z-axis and body diagonal). When the P-point moves, the farther the P-point is, the greater the degree of anisotropy is. The introduction of anisotropy will cause the structural bifurcation of the three-dimensional PM to change structural parameters, and the structural parameters are important factors affecting the band characteristics of the three-dimensional PM of Bragg scattering. In order to study the influence of anisotropy on the band structure and pentamode properties of three-dimensional asymmetric double-cone PMs, we use the finite element simulation software COMSOL to calculate the primitive-cell of three-dimensional anisotropic PMs under Bloch boundary conditions. By adjusting the position of P point, four different types of three-dimensional anisotropic asymmetric double-cone PMs are constructed. Since the anisotropy changes in different directions have different effects on the parameters of the asymmetric double-cone structure, the band characteristics and the pentamode characteristics will also receive different degrees of influence. In this paper, the relationship between the degree of anisotropy and the band gap characteristics, single-mode region and figure of merit (FOM) are given, and the result can provide guidance for the design of asymmetric double-cone PM acoustic device. Compared with the isotropic double-cone PMs, the relative bandwidth of the first band gap of the anisotropic double-cone PMs can be broadened to 123%, and the FOM can be increased to 6.9 times. Due to the introduction of anisotropy, Due to the introduction of anisotropy, the structure of three-dimensional asymmetric double-cone PMs are more complex, the demand for sample fabrication is further improved, and the stability of PMs also reduced. Therefore, PMs with high stability and easy to be fabricated still needs further research and exploration.

A discrete observer-based repetitive control (RC) design method for a linear system with uncertainties was presented based on two-dimensional (2D) system theory. Firstly, a 2D discrete model was established to describe both the control behavior within a repetition period and the learning process taking place between periods. Next, by converting the designing problem of repetitive controller into one of the feedback gains of reconstructed variables, the stable condition was obtained through linear matrix inequality (LMI) and also the gain coefficient of repetitive system. Numerical simulation shows an exceptional feasibility of this proposal with remarkable robustness and tracking speed.

It is clear that activated β3-adrenoceptor can improve disorders of lipid metabolism, however there are few reports concerning the anti-atherosclerotic effects of β3-adrenoceptor in the artery of apolipoprotein E knockout (Apoe−/−) mice. In the present study, we aimed at investigating the effects of β3-adrenoceptor on lipids, atherosclerosis plaques, scavenger receptor class B type 1 and its signal transduction in Apoe−/− mice. Ten C57BL/6J mice were used as a control, and fifty age-matched Apoe−/− mice were randomly divided into five groups: atherosclerotic model (saline), positive control (atorvastatin), low-dose β3-adrenoceptor agonist, high-dose β3-adrenoceptor agonist and β3-adrenoceptor antagonist groups. After 26 weeks on the high-fat diet, the mice received the above treatments for 12 weeks. Thoracic aortas, serum lipids, SR-B1, P-MeK1/2, P-ErK1/2 and protein kinase Cα(PKCα) activity were detected. We found that the levels of serum total cholesterol, triglyceride, very low-density lipoprotein/low-density lipoprotein cholesterol and the area of atherosclerotic plaques were significantly decreased in β3-adrenoceptor agonist-treated mice (P

To examine the effects of β3-adrenoceptor (β3-AR) activation on atherosclerotic plaque development in ApoE(-/-) mice.Thirty six week-old male ApoE(-/-) mice on a high-fat diet were treated with atorvastatin (10 mg·kg(-1)·d(-1), po), BRL37344 (β3-AR agonist, 1.65 or 3.30 μg/kg, ip, twice a week) or SR52390A (β3-AR antagonist, 50 μg/kg, ip, twice a week) for 12 weeks. Wild-type C57BL/6J mice receiving a normal diet were taken as healthy controls. At the end of the treatments, serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol (nHDL-C), glucose and insulin were measured. The thoracic aortas were dissected out, the area of atherosclerotic plaques and extent of fibrosis in the plaques were examined using HE and Masson's trichome staining, respectively.Compared to wild-type mice, ApoE(-/-) mice fed on a high-fat diet exhibited prominent hyperlipidemia and insulin resistance, associated with large area of atherosclerotic plaques and great extent of fibrosis in aortas. Atorvastatin significantly decreased the serum levels of TC and nHDL-C, and reduced the plaque area and collagen content in aortas. BRL37344 significantly decreased the serum levels of TG, TC, nHDL-C, glucose and insulin, and increased HDL-C and the insulin sensitivity, and dose-dependently reduced the plaque area and collagen content in aortas. SR52390A treatment did not affect any parameters studied.The β3-AR agonist impedes the progression of atherosclerosis in ApoE(-/-) mice, through improvement of the lipid and glucose profiles.

Oxymatrine, the main alkaloid component in the traditional Chinese herbal medicine Sophora japonica (Sophora flavescens Ait), has been reported to have antitumor properties. However, the mechanisms of action in human pancreatic cancer are not well established to date. In the present study, we investigated the antiangiogenic effects of oxymatrine on human pancreatic cancer as well as the possible mechanisms involved. The results of the cell viability assay showed that treatment of PANC-1 pancreatic cancer cells with oxymatrine resulted in cell growth inhibition in a dose- and time-dependent manner. To investigate the possible mechanisms involved in these events, we performed western blotting and reverse transcription-polymerase chain reaction (RT-PCR) analysis. The results revealed that oxymatrine decreased the expression of angiogenesis-associated factors, including nuclear factor κB (NF-κB) and vascular endothelial growth factor (VEGF). Finally, the antiproliferative and antiangiogenic effects of oxymatrine on human pancreatic cancer were further confirmed in pancreatic cancer xenograft tumors in nude mice. In conclusion, our studies for the first time suggest that oxymatrine has potential antitumor effects on pancreatic cancer via suppression of angiogenesis, probably through regulation of the expression of the NF-κB-mediated VEGF signaling pathway.

In this study, we investigated the apoptotic effect of emodin on human pancreatic cancer cell line Panc-1 in vitro and in vivo as well as the possible mechanisms involved. In vitro, human pancreatic cancer cell line Panc-1 was exposed to varying concentrations of emodin (0, 10, 20, 40 or 80 µmol/l). Then the mitochondrial membrane potential (MMP) was analyzed by JC-1 staining, cell apoptosis was analyzed by flow cytometry (FCM) and cell proliferation was analyzed by MTT. In vivo, nude mice orthotopically implanted were randomly divided into five groups to receive treatments by different doses of emodin: control group (normal saline 0.2 ml), E10 group (emodin 10 mg/kg), E20 group (emodin 20 mg/kg), E40 group (emodin 40 mg/kg) and E80 group (emodin 80 mg/kg). Each mouse was treated 5 times by intraperitoneal injection of emodin every 3 days. During the treatment, the feeding stuff was recorded. One week after the last treatment, we recorded the body weight and the maximum diameter of tumor in each group before the mice were sacrificed. Then the cell apoptosis of the tumor was tested by TUNEL assay. The results in vitro showed that the MMP of the cells declined and the apoptosis rate increased with the emodin concentration increasing and the cell proliferation of each group was inhibited in a dose- and time-dependent manner by emodin. The feeding stuff curve did not decline significantly in E40 group and the apoptosis rate of the tumor cells in this group was higher than the lower-dose groups. Taken together, our results demonstrate that emodin may induce the pancreatic cancer cell apoptosis via declining the MMP and a moderate dose of emodin improved the living state of the model mice.

Gemcitabine is currently the best treatment available for pancreatic cancer (PaCa); however, patients with the disease develop resistance to the drug over time. Agents that can either enhance the effects of gemcitabine or overcome chemoresistance to the drug are required for the treatment of PaCa. Oridonin is one such agent which is safe and multitargeted, and has been linked with the suppression of survival, proliferation, invasion and angiogenesis of cancer. In this study, we investigated whether oridonin could sensitize PaCa to gemcitabine in vitro and in vivo. In vitro, oridonin inhibited the proliferation of the PaCa cell line, BxPC-3, potentiated the apoptosis induced by gemcitabine, induced G1 cell cycle arrest and activated p38 and p53; these results were significant when oridonin was combined with gemcitabine. In vivo, we found that oridonin significantly suppressed tumor growth and this effect was further enhanced by gemcitabine (P

Evodiamine has therapeutic potential against cancers. This study was designed to investigate whether combination therapy with gemcitabine and evodiamine enhanced antitumor efficacy in pancreatic cancer. In vitro application of the combination therapy triggered significantly higher frequency of pancreatic cancer cells apoptosis, inhibited the activities of PI3K, Akt, PKA, mTOR and PTEN, and decreased the activation of NF-κB and expression of NF-κB-regulated products. In vivo application of the combination therapy induced significant enhancement of tumor cell apoptosis, reductions in tumor volume, and inhibited activation of mTOR and PTEN. In conclusion, evodiamine can augment the therapeutic effect of gemcitabine in pancreatic cancer through direct or indirect negative regulation of the PI3K/Akt pathway.

The similar normal distribution is used wildly in the natural science and social science, fuzzy membership degree function which is accurately established seriously reduces the forecast accuracy of such data. Cloud model compare randomness and fuzziness organically, it reveal the relevance between randomness and fuzziness with digital expectations, entropy and hyper entropy, forecast algorithm based on normal cloud model relaxed the requirements of a normal distribution prerequisite and replaced the accurate membership degree function with the membership degree distribution expectation function, it is more easier and simpler than the joint distribution, Comparative experiment showed it is more general, can complete the data forecast accurately and directly.

An HPLC method has been developed for the simultaneous determination of the toxic Aconitum alkaloids, aconitine, mesaconitine and hypaconitine in blood and urine samples. The samples were initially subjected to solid phase extraction using Oasis® MCX cartridges, and the alkaloids were separated on an XTerra™ RP18 column, gradient-eluted with acetonitrile: ammonium hydrogen carbonate buffer. Calibration curves were linear in the range 2.75–550 ng for aconitine and hypaconitine, and 3–600 ng for mesaconitine: the limit of detection was 0.1 ng (signal-to-noise ratio of 3) for each alkaloid. The described analysis proved to be sensitive, rapid and economical, and will be applied in the identification and determination of these alkaloids in forensic and therapeutic drug monitoring. Copyright © 2004 John Wiley & Sons, Ltd.

The beta-3 adrenoceptor (β3-AR) protects against the progression of atherosclerosis. However, the specific mechanism of this antiatherosclerotic effect is still not clear. Thus, the aim of this study was to understand the antiatherosclerotic effects of β3-AR. Thirty-six male homozygous apolipoprotein E-deficient mice and wild-type C57BL/6J mice were randomized into 6 treatment groups: wild-type, atherosclerotic model, atorvastatin, low-dose β3-AR agonist, high-dose β3-AR agonist, and β3-AR antagonist groups. The serum lipids, aortic-free cholesterol (FC), and cholesteryl ester (CE) concentrations were measured at the end of the treatments. The mRNA expression levels of liver apolipoprotein A-I (apoA-I), peroxisome proliferator-activated receptor-α (PPARα), and peroxisome proliferator-activated receptor-γ (PPARγ) were detected by quantitative real-time PCR. Protein expression levels of apoA1, PPARα, and PPARγ in the liver were determined by western blot analysis. Treatment with β3-AR significantly increased the plasma levels of high-density lipoprotein cholesterol and apoA-I, whereas the levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol decreased. The β3-AR agonist treatment markedly decreased both the FC and the CE concentrations in the aorta compared with the atherosclerotic model mice. The β3-AR agonist increased the mRNA and protein expression levels of apoA-I, PPARα, and PPARγ in the liver. This study demonstrates that long-term β3-AR activation can regulate lipid metabolic disorders and reduces the aortic FC and the CE concentrations. These effects may be related to apoA-I, PPARα, and PPARγ.

Emodin is a traditional Chinese medicine, which has been demonstrated to inhibit the growth of pancreatic cancer cells. However, the underlying molecular mechanisms remain to be elucidated. The present study investigated whether emodin suppresses angiogenesis in pancreatic cancer. A nude mouse pancreatic cancer xenograft model was established using SW1990 human pancreatic cancer cells by surgical orthotopic implantation. Different doses of emodin were injected into the abdominal cavities of the tumor‑bearing mouse models and controls three times each week for 2 weeks. The tumors were measured and weighed, the expression of cluster of differentiation 34 was detected using immunochemistry, and microvessel densities were calculated. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were performed to determine the mRNA and protein expression levels of transforming growth factor (TGF)‑β and drosophila mothers against decapentaplegic (Smad) homologs. The angiogenesis‑associated microRNAs (miR), miR‑20, miR‑155 and miR‑210 were assessed by RT‑qPCR. A negative dose‑dependent association was revealed between treatment with emodin and the volume and weight of tumors and microvessel density. Emodin was associated with lower mRNA and protein expression levels of TGF‑β1 and its downstream target, angiopoietin‑like 4, and higher mRNA and protein expression levels of TGF‑β receptor (TβR)I, TβRII and Smad4. Notably, treatment with emodin was associated with lower expression levels of miR‑155 and miR‑210 and higher expression levels of miR‑20b. The present study suggested that treatment with emodin may repress angiogenesis in pancreatic cancer by altering the activities of the TGF-β/Smad pathway and angiogenesis-associated miR-20b, miR-155, and miR-210.

Ginsenoside Rg3 (Rg3), a trace tetracyclic triterpenoid saponin, is extracted from ginseng and shown to have anticancer activity against several types of cancers. This study explored the effect of Rg3 on pancreatic cancer vasculogenic mimicry. Altered vasculogenic mimicry formation was assessed using immunohistochemistry and PAS staining and associated with the expression of vascular endothelial-cadherin (VE-cadherin), epithelial cell kinase (EphA2), matrix metalloproteinase (MMP)-2 and MMP-9. The effect of Rg3 on the regulation of pancreatic cancer vasculogenic mimicry was evaluated in vitro and in vivo. The data showed vasculogenic mimicry in pancreatic cancer tissues. In addition, the expression of VE-cadherin, EphA2, MMP-2 and MMP-9 proteins associated with formation of pancreatic cancer vasculogenic mimicry. Rg3 treatment reduced the levels of vasculogenic mimicry in nude mouse xenografts in vitro and in vivo, while the expression of VE-cadherin, EphA2, MMP-2 and MMP-9 mRNA and proteins was downregulated by Rg3 treatment in vitro and in tumor xenografts. In conclusion, ginsenoside Rg3 effectively inhibited the formation of pancreatic cancer vasculogenic mimicry by downregulating the expression of VE-cadherin, EphA2, MMP9 and MMP2. Further studies are required to evaluate ginsenoside Rg3 as an agent to control pancreatic cancer.

To establish a method for the content determination of indexes for measuring aconitic compounds contained in Shenfu injection, in order to provide basis for the evaluation of the curative effect of monkshood in Shenfu injection. The sample were purified and enriched with HF-LPME. ACQUITY UPLC BEH C18 column (2.1 mm x 50 mm, 1.7 microm) was adopted and eluted with a gradient program, with acetonitrile-10 mmol x L(-1) NH4HCO3 (pH 10) as the mobile phases. The flow rate was 0.45 mL x min(-1). The content was determined with ESI and MRM. The results showed that aconitine, hypaconitine and mesaconitine showed a good linear relationship, with r0.999, within the range of 0.1-100 ng x L(-1). The recoveries were detected to be 100.1%, 97.4%, 97.5%, with RSD being 1.2%, 1.1%, 1.5%, respectively. This method was used to prove the safety of Shenfu injection, and provide scientific basis for correct evaluation of curative effect of monkshood, as well as a reliable, simple and practical means for quality control of monkshood-containing Chinese materia medica preparations.

To analyze the advantages and disadvantages of bipedicular approach and uni-extrapedicular approach of vertebroplasty in treating osteoporotic vertebral compression fractures (OVCFs).From January 2008 to December 2010,53 patients with OVCFs were retrospectively analyzed. There were 24 males, 30 females with an average age of 66.9 years (ranged,59 to 88 years). Among them, 26 cases were treated with bipedicular approach, 28 cases were treated with uni-extrapedicular approach. The data of bone cement injection, radiology exposure times, operation time, bone cement leakage and vessels nerve complications were observed. Cobb angle, vertebral compression ration were observed by imaging data, and evaluate recovery of deformity.The data of bone cement injection, radiology exposure times, operation time, VAS score were (6.6 +/- 0.8) ml and (6.8 +/- 1.5) ml, (21.7 +/- 4.0) times and (17.9 +/- 3.6) times, (40.5 +/- 5.5) min and (31.6 +/- 9.1) min, (2.8 +/- 0.6) scores and (3.1 +/- 0.5) scores respectively. Cobb angle,vertebral compression ration were (7.6 +/- 2.0) degrees and (6.9 +/- 2.6) degrees, (18.1 +/- 5.8)% and (16.5 +/- 6.1)%. There were no vascular nerve complications occurred. For bone cement leakage, 3 cases (11%) in bipedicular approach and 3 cases (11%)in uni-extrapedicular approach. There was no significant differences between two groups in VAS score, recovery of vetebral body, Cobb angle, bone cement injection and bone cement leakage, but had significant differences in radiology exposure times and operation time (P0.05).Both of two approaches can treat OVCFs well, especially extropedicle approach which could reduce operation time and radiation shoot frequency.

Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in bothin vitroandin vivosystems, as well as the possible mechanisms involved.In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990) with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153), a marker of the endoplasmic-reticulum-stress- (ERS-) mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover,in vivostudies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78), phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK), and phosphoeukaryotic initiation factor-2α(phospho-eIF2α), activating transcription factor 4 (ATF4) and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.

To assess the clinical and radiographic outcomes of posterior lumbar fixation and posterior interbody fusion or improved transforaminal lumbar interbody fusion for Meyerding grade II/III spondylolisthesis so as to address the suitability of a dynamic stabilization.A total of 28 consecutive patients underwent posterior lumbar fixation and posterior interbody fusion or improved transforaminal lumbar interbody fusion for Meyerding grade II/III spondylolisthesis. Among them, 13 patients underwent posterior interface fusion (PLIF) and pedicle screw fixation. And improved transforaminal lumbar interbody fusion (ITLIF) and placement of the same system were performed in 15 patients. Their clinical, economic, functional, and radiographic data were recorded both pre- and postoperatively.The average changes of economic and functional scores on the Prolo scale were 1.36 and 1.48 respectively. In patients with posterior interbody fusion; the average preoperative vertebral slippage was 46.9% (range: 25 - 75%) versus 14.6% (range: 15 - 25%) postoperatively. In patients with ITLIF, the average changes in economic and functional scores were 1.75 and 1.63 respectively. And the average preoperative vertebral slippage was 45.2% (range: 28 - 78%) compared with 26.3% (range: 14 - 28%) postoperatively. When two fusion techniques were compared, an overall superior reliability and resistance of systems was associated with the ITLIF procedure. But their clinical outcomes did not differ greatly (P0.05).The application of a segmental pedicle screw fixation is both feasible and efficacious.

Background Emodin has been showed to induce apoptosis of pancreatic cancer cells and inhibit tumor growth in our previous studies. This study was designed to investigate whether emodin could inhibit the angiogenesis of pancreatic cancer tissues and its mechanism. Methodology/Principal Finding In accordance with our previous study, emodin inhibited pancreatic cancer cell growth, induced apoptosis, and enhanced the anti-tumor effect of gemcitabine on pancreatic caner cells in vitro and in vivo by inhibiting the activity of NF-κB. Here, for the first time, we demonstrated that emodin inhibited tumor angiogenesis in vitro and in implanted pancreatic cancer tissues, decreased the expression of angiogenesis-associated factors (NF-κB and its regulated factors VEGF, MMP-2, MMP-9, and eNOS), and reduced eNOS phosphorylation, as evidenced by both immunohistochemistry and western blot analysis of implanted tumors. In addition, we found that emodin had no effect on VEGFR expression in vivo. Conclusions/Significance Our results suggested that emodin has potential anti-tumor effect on pancreatic cancer via its dual role in the promotion of apoptosis and suppression of angiogenesis, probably through regulating the expression of NF-κB and NF-κB-regulated angiogenesis-associated factors.

Pancreatic cancer is a highly aggressive malignant disease. Gemcitabine is currently the standard first-line chemotherapeutic agent for pancreatic cancer. As members of apoptosis inhibitors, Survivin and XIAP play an important role in chemotherapy resistance in pancreatic cancer. Emodin has therapeutic potential against cancers. This study was designed to investigate whether combination therapy with gemcitabine and emodin enhanced antitumor efficacy in pancreatic cancer. The application of the combination therapy triggered significantly higher frequency of pancreatic cancer cell apoptosis. Our research demonstrated that the combination of emodin and gemcitabine resulted in significantly reduced tumor volumes compared to gemcitabine or emodin treatment alone. Immunohistochemistry and western immunoblot analyses showed that Survivin and XIAP expression were downregulated in emodin and the combination groups compared to the other two groups. Reverse transcriptase polymerase chain reaction analyses showed that Survivin and XIAP mRNA expression in emodin and the combination groups were downregulated significantly compared to the other two groups. Furthermore, the expression of the nuclear transcription factor κB (NF-κB) protein and NF-κB mRNA were downregulated in the emodin and the combination groups. DNA-binding activity of NF-κB was inhibited in emodin and combination groups compared to the other groups. This study suggests that emodin potentiates the antitumor effects of gemcitabine in PANC-1 cell xenografts via promotion of apoptosis and IAP suppression.

To evaluate the clinical efficacies, indications and application values of posterior fusion plus pedicle screw fixation in the treatment of upper cervical spine instability.From May 2006 to December 2010, a total of 24 patients with atlantoaxial instability were treated with C1-2 pedicle screws and rod fixation under general anesthesia. There were 18 males and 6 females with a mean age of 49.8 years old (range: 17 - 69).The postoperative radiographs verified a good position of all screws with satisfactory atlantoaxial reduction. A mean follow-up period of 23 months (range: 3 - 45) showed no injury of spinal cord and vertebral artery or inter fixation failure. Atlantoaxial alignment and stability were restored without instrumentation-related complications.Posterior atlantoaxial pedicle screw and rod fixation provide immediate three-dimensional rigid fixation of atlantoaxial joint. It is a more effective technique than with previously reported techniques.

To study the outcomes of very or extremely low birth weight (VLBW/ELBW) infants born between 2000 and 2008 in a single NICU and the medical factors associated with the termination of treatment in some infants.In this case control study, the clinical data of 148 VLBW/ELBW infants were retrospectively studied and the surviving infants were followed up. Both univariate analysis and multivariate logistic regression analysis were used to investigate the medical factors associated with terminating treatment in infants.Twenty infants (13.5%) failed to respond to the therapy and died in the hospital. Three infants (2.0%) died after discharge. Nineteen infants (12.8%) did not receive treatment due to decision of the guardian and died. Thirty infants (20.3%) were not followed up after discharge. Seventy-six infants (51.4%) survived, including 47 healthy infants, 2 cases of congenital diseases and 27 cases with poor prognosis. Multivariate logistic regression analysis showed there were 2 significant factors associated with terminating treatment: neonatal respiratory distress syndrome (P=0.030, OR=11.396, 95%CI 1.-102.701) and hospitalization periods (the year 2004-2006) (P=0.039, OR=9.869, 95%CI 1.118-87.140).The survival status of VLBW and ELBW infants needs to be improved. It is important to decrease the incidence of neonatal respiratory distress syndrome for decreasing the proportion of terminating treatment in the infants.

Gemcitabine resistance is a common problem of pancreatic cancer chemotherapy, and how to reverse it plays an important role in the treatment of pancreatic cancer. This study investigated the effect of emodin on the gemcitabine-resistant pancreatic cancer cell line SW1990/Gem, and explored the potential mechanism of its action. SW1990/Gem was obtained by culture of the pancreatic cancer cell line SW1990 in vitro by intermittently increasing the concentration of gemcitabine in the culture medium for 10 months, observing the morphology using inverted microscopy. SW1990/Gem cells were pretreated with emodin (10 µM) for different periods followed by treatment with gemcitabine (20 µM) for 48 h; cell proliferation was tested by MTT assay. SW1990/Gem cells were treated by emodin with different concentrations for 48 h, cell apoptosis was detected by flow cytometry (FCM). The expression of gene and protein, such as MDR-1 (P-gp), NF-κB, Bcl-2, Bax, cytochrome-C (cytosol), caspase-9 and -3 were measured by RT-PCR and Western blotting. The function of P-gp in SW1990/Gem cells was checked by FCM. The results showed that the SW1990/Gem cells changed greatly in morphology and the resistance index was 48.63. Emodin promoted cell apoptosis of the gemcitabine-resistant cell line SW1990/Gem in a dose-dependent manner. Emodin enhanced the SW1990/Gem cell sensitivity to gemcitabine in a time-dependent manner. Emodin monotherapy or combination with gemcitabine both decreased the gene and protein expression levels of MDR-1 (P-gp), NF-κB and Bcl-2 and inhibited the function of P-gp, but increased the expression levels of Bax, cytochrome-C (cytosol), caspase-9 and -3, and promoted cell apoptosis. This demonstrated that emodin had a reversing effect on the gemcitabine-resistant cell line SW1990/Gem, possibly via decreasing the function of P-gp and activating the mitochondrial apoptosis pathway in vitro.

XIAP and NF-κB play an important role in chemotherapy resistance in pancreatic cancer. The purpose of this study was to explore the role of XIAP and NF-κB in potentiating the antitumor effect of gemcitabine by emodin in pancreatic cancer. SW1990 cells were treated by sodium chloride, gemcitabine, emodin or their combination (gemcitabine plus emodin). Cellular proliferation and apoptosis were detected by Cell Counting kit-8 (CCK-8) assay and flow cytometry in vitro. The combination therapy more significantly inhibited SW1990 cell growth and induced a higher percentage of apoptosis than monotherapy. Gemcitabine upregulated the expression of XIAP and NF-κB, while emodin or emodin plus gemcitabine downregulated them compared to the control group in vitro. SW1990 cells were used to establish orthotopic pancreatic tumor models in nude mice. Tumor-bearing mice were treated with sodium chloride, emodin, gemcitabine or their combination. After being treated for 4 weeks, the nude mice were imaged with high-resolution positron emission tomography (microPET) and fluorine-18-labeled fluorodeoxyglucose (18F-FDG) to detect the tumor/non-tumor ratio (T/NT ratio) and standard uptake value (SUV). The mice were sacrificed to determine tumor weight. The combination of emodin and gemcitabine showed more significant reduction in the T/NT ratio, SUV and tumor weight compared to monotherapy. The mRNA levels and the protein expression of XIAP and NF-κB were upregulated in the gemcitabine group, while they were downregulated in the emodin group and the combination group in vivo. Ki-67 prolif-eration index and TUNEL assay results also showed that emodin enhanced tumor apoptosis induced by gemcitabine in vivo. This study suggests that emodin enhances the antitumor effect of gemcitabine in SW1990 pancreatic cancer in vitro and in vivo, which may be via the downregulation of NF-κB expression, thus inhibiting the expression of XIAP.

In view of gemcitabine resistance has limited clinical activity of gemcitabine as a cellulotoxic drug in pancreatic cancer patients, this study is designed to investigate the effect of emodin on the sensitivity of pancreatic cancer to gemcitabine as well as its mechanism. After gemcitabine-resistant pancreatic cancer cell line (SW1990/GZ) was established by escalating doses of gemcitabine serially in pancreatic cancer cell line (SW1990). The cellular proliferation was detected by cell counting kit-8 (CCK-8) assay. Flow cytometry (FCM) was used to determine apoptosis of pancreatic cancer cells. The activity of NF-kappaB in pancreatic cancer cells was measured by electrophoretic mobility shift assay (EMSA). Western blotting was used to detect the protein expression of Bcl-2 and Survivin in SW1990/GZ cells. Metastatic model simulating human pancreatic cancer was established by orthotopic implantation of histologically intact human tumor tissue into pancreatic wall of nude mice. Also, immunohistochemistry was used to detect the positive expression of Ki-67, NF-kappaB, Bcl-2 and Survivin in the tumors. The results show that pretreatment of cells with emodin followed by gemcitabine induced a higher percentage of growth inhibition and apoptosis of pancreatic cancer cells than that of gemcitabine alone. In addition to in vitro results, emodin in combination with gemcitabine is much more effective as an antitumor agent compared to either agent alone in the orthotopic tumor model. Further study showed that the emodin with or without gemcitabine significantly down-regulates NF-kappaB and its regulated molecules such as Bcl-2 and Survivin proteins both in vitro and in vivo. It is concluded that inactivation of NF-kappaB signaling pathway by emodin resulting in the chemosensitization of pancreatic cancer to gemcitabine, which is likely to be an important and novel strategy for the treatment of pancreatic cancer.

Pancreatic adenocarcinoma is one of the most common malignancies worldwide. Gemcitabine is currently the standard first-line chemotherapeutic agent for pancreatic cancer. However, gemcitabine can induce activation of Akt and nuclear factor-κB (NF-κB), which is associated with its chemoresistance. It has been reported that gemcitabine combination therapies result in improved survival outcomes in pancreatic cancer. Therefore, agents that can either enhance the effects of gemcitabine or overcome chemoresistance to the drug are needed for the treatment of pancreatic cancer. Emodin is an active component of Chinese medicinal herbs and can inhibit the activation of Akt and NF-κB. In this study, we investigated whether emodin could enhance the anticancer effect of gemcitabine on pancreatic cancer in vivo. We demonstrated that treatment of gemcitabine combined with emodin efficiently suppressed tumor growth in mice inoculated with pancreatic tumor cells. This treatment paradigm promoted apoptotic cell death and mitochondrial fragmentation. Furthermore, it reduced phosphorylated-Akt (p-Akt) level, NF-κB activation and Bcl-2/Bax ratio, increased caspase-9 and -3 activation, Cytochrome C (CytC) release occurred in combination therapy. Collectively, emodin enhanced the activity of gemcitabine in tumor growth suppression via inhibition of Akt and NF-κB activation, thus promoting the mitochondrial-dependent apoptotic pathway. Therefore, our findings may provide new insights into understanding the pharmacological regulation of emodin on gemcitabine-mediated proapoptosis in pancreatic cancer and may aid in the design of new therapeutic strategies for the intervention of human pancreatic cancers.