Clopidogrel resistance response in patients with coronary artery disease and metabolic syndrome： the role of hyperglycemia and obesity

Background Despite the proven benefits of clopidogrel combined aspirin therapy for coronary artery disease （CAD）, CAD patients with metabolic syndrome （MS） still tend to have coronary thrombotic events. We aimed to investigate the influence of metabolic risk factors on the efficacy of clopidogrel treatment in patients with CAD undergoing percutaneous coronary intervention （PCI）. Methods Cohorts of 168 MS and 168 non-MS subjects with CAD identified by coronary angiography （CAG） were enrolled in our study. MS was defined by modified Adult Treatment Panel Ⅲ criteria. All subjects had taken 100 mg aspirin and 75 mg clopidogrel daily for more than 1 month, and administered loading doses of 600 mg clopidogrel and 300 mg aspirin before PCI. Blood samples were taken 24 h after the loading doses of clopidogrel and aspirin. Platelet aggregation was measured using light transmittance aggregometry （LTA） and thrombelastography （TEG）. Clopidogrel resistance was defined as more than 50% adenosine diphosphate （ADP） induced platelet aggregation as measured by TEG. Re- sults Platelet aggregation inhibition rate by ADP was significantly lower in patients with MS as measured both by TEG （55% ＋ 31% vs. 68% ± 32%; P 〈 0.001） and LTA （29% ± 23% vs. 42% ± 29%; P 〈 0.001）. In the multivariate analysis, elderly [OR （95% CI）： 1.483 （1.047±.248）; P = 0.002], obesity [OR （95% CI）： 3.608 （1.241-10.488）; P = 0.018], high fasting plasma glucose level [OR （95% CI）： 2.717 （1.176±.277）; P = 0.019] and hyperuricemia [OR （95% CI）： 2.583 （1.095-6.094）; P = 0.030] were all statistically risk factors for clopido- grel resistance. CAD patients with diabetes and obesity were more likely to have clopidogrel resistance than the CAD patients without dia- betes and obesity [75% （61/81） vs. 43% （67/156）; P 〈 0.001]. Conclusions CAD patients with MS appeared to have poorer antiplatelet response to clopidogrel compared to those without MS. Obesity, diabetes and hyperuricemia were all significantly associated with clopido- grel resistance.

Autonomous maneuver decision-making for a UCAV in short-range aerial combat based on an MS-DDQN algorithm

To solve the problem of realizing autonomous aerial combat decision-making for unmanned combat aerial vehicles(UCAVs) rapidly and accurately in an uncertain environment, this paper proposes a decision-making method based on an improved deep reinforcement learning(DRL) algorithm: the multistep double deep Q-network(MS-DDQN) algorithm. First, a six-degree-of-freedom UCAV model based on an aircraft control system is established on a simulation platform, and the situation assessment functions of the UCAV and its target are established by considering their angles, altitudes, environments, missile attack performances, and UCAV performance. By controlling the flight path angle, roll angle, and flight velocity, 27 common basic actions are designed. On this basis, aiming to overcome the defects of traditional DRL in terms of training speed and convergence speed, the improved MS-DDQN method is introduced to incorporate the final return value into the previous steps. Finally, the pre-training learning model is used as the starting point for the second learning model to simulate the UCAV aerial combat decision-making process based on the basic training method, which helps to shorten the training time and improve the learning efficiency. The improved DRL algorithm significantly accelerates the training speed and estimates the target value more accurately during training, and it can be applied to aerial combat decision-making.

Atypical presentation of shoulder brucellosis misdiagnosed as subacromial bursitis:A case report

BACKGROUND Brucella infections in the shoulder joint are uncommon,and few have been reported in the literature.CASE SUMMARY A 26-year-old male was admitted to our hospital with complaint of recurrent pain and limited movement of the right shoulder.The patient reported the pain to have first occurred as an isolated event 6 mo previously and to have reoccurred 5 mo later,when it was accompanied by limited movement of the shoulder.Findings from physical examination and magnetic resonance imaging(referred to as MRI)suggested the diagnosis of subacromial bursitis,and diagnostic paracentesis and arthroscopic debridement were performed.Surprisingly,synovial fluid culture detected brucella,and the finding was confirmed by mass spectrometry of a colony sample.The diagnosis was corrected to brucellosis of the shoulder joint,and antibiotic drug treatment(oral rifampicin and doxycycline)was administrated for 6 wk.The 4-mo postoperative follow-up examination(MRI)yielded normal findings.The 2-year follow-up showed no signs of recurrence.CONCLUSION This rare case of brucellosis infection in shoulder highlights the importance of increasing awareness to help avoid misdiagnosis.

Adenovirus expressing p27^(kip1) suppresses growth of established esophageal carcinoma xenografts

AIM： TO investigate the growth suppression of adenovirus expressing p27^kip1 on established esophageal tumors in nude mice. METHODS： Esophageal carcinoma xenografts in nude mice were established by tumor tissue mass transplantation. The successfully constructed recombinant adenoviral vectors carrying p2^kip1 gene （Ad- p27^%kip1） were directly injected into the esophageal tumors in nude mice. Compared to control group, the growth curve of tumor was drawn and the growth inhibition rate of tumor was calculated. The histology of tumors was examined by hematoxylin and eosin （H＆E） staining. The expression of p27^kip1 and survivin was detected in tumors by immunohistochemical technique. RESULTS： The growth of tumors in gene therapy group with Ad-p27^kip1 was obviously suppressed compared to control group （0.42±0.08 g vs 1.17±0.30 g, t=6.39, P〈0.01）, the inhibition rate of tumor growth reached 64.1%. Pathological detection showed that the tumors in nude mice were poorly differentiated esophageal squarnous carcinoma. In addition, the expression of p27^kip1 was increased, while the expression of survivin was decreased in tumors after being transfected with Ad-p27^kip1. CONCLUSION： p27^kip1 gene therapy mediated by adenovirus vector has a significant inhibitory effect on esophageal carcinoma in vivo. Up-regulated p27^kip1 expression and down-regulated survivin expression may be its important mechanisms.

RAPID EXPANSION OF SECURITIES MARKET&ITS IMPACT ON ACCOUNTING PROFESSION

Ⅰ.EXPANSIONThe establishment of securities market in China has been considered one of its important and controversial economic reform policies.Billions of dollars of treasury bills,corporate bonds and shares have been issued and traded all over the nation.Securities exchanges were set up in Shanghai and Shenzhen by the end of 1990 and in early 1991.Since then,securities market in China has undergone rapid expansion.

Approximate Analytical Solution of the Generalized Kolmogorov-Petrovsky-Piskunov Equation with Cubic Nonlinearity

In this paper,the approximate analytical oscillatory solutions to the generalized KolmogorovPetrovsky-Piskunov equation(gKPPE for short)are discussed by employing the theory of dynamical system and hypothesis undetermined method.According to the corresponding dynamical system of the bounded traveling wave solutions to the gKPPE,the number and qualitative properties of these bounded solutions are received.Furthermore,pulses(bell-shaped)and waves fronts(kink-shaped)of the gKPPE are given.In particular,two types of approximate analytical oscillatory solutions are constructed.Besides,the error estimations between the approximate analytical oscillatory solutions and the exact solutions of the gKPPE are obtained by the homogeneity principle.Finally,the approximate analytical oscillatory solutions are compared with the numerical solutions,which shows the two types of solutions are similar.

Approximate Damped Oscillatory Solutions for Compound KdV-Burgers Equation and Their Error Estimates

In this paper, we focus on studying approximate solutions of damped oscillatory solutions of the compound KdV-Burgers equation and their error estimates. We employ the theory of planar dynamical systems to study traveling wave solutions of the compound KdV-Burgers equation. We obtain some global phase portraits under different parameter conditions as well as the existence of bounded traveling wave solutions. Furthermore, we investigate the relations between the behavior of bounded traveling wave solutions and the dissipation coefficient r of the equation. We obtain two critical values of r, and find that a bounded traveling wave appears as a kink profile solitary wave if │r│ is greater than or equal to some critical value, while it appears as a damped oscillatory wave if │r│is less than some critical value. By means of analysis and the undetermined coefficients method, we find that the compound KdV-Burgers equation only has three kinds of bell profile solitary wave solutions without dissipation. Based on the above discussions and according to the evolution relations of orbits in the global phase portraits, we obtain all approximate damped oscillatory solutions by using the undetermined coefficients method. Finally, using the homogenization principle, we establish the integral equations reflecting the relations between exact solutions and approximate solutions of damped oscillatory solutions. Moreover, we also give the error estimates for these approximate solutions.

Comparative Study on Solid-State and Metastable Liquid-State Aging for SAC305/Cu Joints

In order to study the in?uence of the physical state of solder on the interfacial reaction of dip-soldered Sn-3.0 Ag-0.5 Cu/Cu system, two kinds of experiments were designed, including:(1) solid-state aging between the solder and Cu substrate;(2)liquid-state aging between the metastable supercooled liquid-state solder and Cu substrate. The aging times were 30, 60,120 and 180 min, respectively, and the aging temperature was 8 ℃ lower than the melting point of the Sn-3.0 Ag-0.5 Cu(SAC305) alloy(217 ℃). The experimental data revealed that the physical state of the solder obviously affected the formation of the intermetallic compound(IMC), and resulted in the difference in the diffusion of atoms on the interface between the SAC305 solder and Cu substrate. The IMC interface after aging for 30 min presents unique characteristics compared with that of the sample after dip soldering. The IMC interface of solid-state aged SAC305/Cu couple is relatively planar, while the IMC interface under metastable supercooled liquid-state aging conditions presents scallop-like shape.

Menaquinone-7 production from maize meal hydrolysate by Bacillus isolates with diphenylamine and analogue resistance

A menaquinone-7（MK-7） high-producing strain needs to be isolated to increase MK-7 production, in order to meet a requirement of MK-7 given the low MK-7 content in food products. This article focuses on developing MK-7 high-producing strains via screening and mutagenesis by an atmospheric and room temperature plasma（ARTP） mutation breeding system. We isolated an MK-7-producing strain Y-2 and identified it as Bacillus amyloliquefaciens, which produced（7.1±0.5） mg/L of MK-7 with maize meal hydrolysate as carbon source. Then, an MK-7 highproducing strain B. amyloliquefaciens H.β.D.R.-5 with resistance to 1-hydroxy-2-naphthoic acid, β-2-thienylalanine, and diphenylamine was obtained from the mutation of the strain Y-2 using an ARTP mutation breeding system. Using strain H.β.D.R.-5, efficient production of MK-7 was achieved（（30.2±2.7） mg/L）. In addition, the effects of nitrogen sources, prenyl alcohols, and MgSO_4 on MK-7 production were investigated, suggesting that soymeal extract combined with yeast extract, isopentenol, and MgSO4 was beneficial. Under the optimized condition, the MK-7 production and biomass-specific yield reached（61.3±5.2） mg/L and 2.59 mg/L per OD600 unit respectively in a 7-L fermenter. These results demonstrated that strain H.β.D.R.-5 has the capacity to produce MK-7 from maize meal hydrolysate, which could reduce the substrate cost.

Antisense RNA: the new favorite in genetic research

Antisense RNA molecule represents a unique type of DNA transcript that comprises 19-23 nucleotides and is complementary to mRNA. Antisense RNAs play the crucial role in regulating gene expression at multiple levels, such as at replication, transcription, and translation. In addition, artificial antisense RNAs can effectively regulate the expression of related genes in host cells. With the development of antisense RNA, investigating the functions of antisense RNAs has emerged as a hot research field. This review summarizes our current understanding of antisense RNAs, particularly of the formation of antisense RNAs and their mechanism of regulating the expression of their target genes. In addition, we detail the effects and applications of antisense RNAs in antivirus and anticancer treatments and in regulating the expression of related genes in plants and microorganisms. This review is intended to highlight the key role of antisense RNA in genetic research and guide new investigators to the study of antisense RNAs.

Asymptotic Stability of Monotone Decreasing Kink Profile Solitary Wave Solutions for Generalized KdV-Burgers Equation

In this paper,we focus on studying the asymptotic stability of the monotone decreasing kink profile solitary wave solutions for the generalized KdV-Burgers equation.We obtain the estimate of the firstorder and second-order derivatives for monotone decreasing kink profile solitary wave solutions,and overcome the difficulties caused by high-order nonlinear terms in the generalized KdV-Burgers equation in the estimate by using L2 energy estimating method and Young inequality.We prove that the monotone decreasing kink profile solitary wave solutions are asymptotically stable in H1.Moreover,we obtain the decay rate of the perturbationψin the sense of L^2 and L^∞norm,respectively,which are(1+t)^-1/2 and(1+t)^-1/4 by using Gargliado-Nirenberg inequality.

Exosomes exist in nipple discharge of breast cancer

Exosomes are a class of membranous vesicles,which are approximately 50 to 100 nm in diameter;they are released into the extracellular matrix from various cells.[1]Exosomes are rich in proteins,lipids,and nucleic acids.They have been reported to be involved in various physiological processes and are important tools for intercellular material and information communication.[2,3]Increasing evidence has indicated that exosomes can be extracted from human saliva,urine,blood,and other body fluids.[4]However,whether exosomes exist in nipple discharge remains unknown.In this study,exosomes from nipple discharge of breast cancer patients and colostrum of postpartum women were isolated using ultracentrifugation.The exosomes were identified by transmission electron microscopy(TEM),Western blot,and nanoparticle tracking analysis(NTA).The detailed methods are shown in Supplementary File 1,http://links.lww.com/CM9/A286.The study was approved by the Ethics Committee of Qilu Hospital of Shandong University(No.KYLL-2018-096),and all patients provided written informed consent.

Preparation of pH-and reductive-responsive prodrug nanoparticles via polymerization-induced self-assembly

pH-and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced selfassembly(PISA). First, reversible addition-fragmentation chain transfer(RAFT) polymerization of 2-(diisopropylamino) ethyl methacrylate(DIPEMA) and camptothecin prodrug monomer(CPTM) using biocompatible poly(N-(2-hydroxypropyl) methacrylamide)(PHPMA-CPDB) as the macro RAFT agent is carried out, forming prodrug diblock copolymer PHPMA-P(DIPEMA-co-CPTM). Then, simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation are achieved via RAFT dispersion polymerization of benzyl methacrylate(Bz MA) using the PHPMA-P(DIPEMA-co-CPTM) as the macro RAFT agent. The prodrug nanoparticles have three layers, the biocompatible shell(PHPMA), the drug-conjugated middle layer(P(DIPEMA-co-CPTM)) and the PBz MA core, and relatively high concentration(250 mg/g). The prodrug nanoparticles can respond to two stimuli(reductive and acidic conditions). Due to reductive microenvironment of cytosol, the cleavage of the conjugated camptothecin(CPT) within the prodrug nanoparticles could be effectively triggered. p H-Induced hydrophobic/hydrophilic transition of the PDIPEMA chains results in faster diffusion of GSH into the CPTM units, thus accelerated release of CPT is observed in mild acidic and reductive conditions. Cell viability assays show that the prodrug nanoparticles exhibit well performance of intracellular drug delivery and good anticancer activity.

Strategies used for genetically modifying bacterial genome: site-directed mutagenesis, gene inactivation, and gene over-expression

With the availability of the whole genome sequence of Escherichia coli or Corynebacterium glutamicum, strategies for directed DNA manipulation have developed rapidly. DNA manipulation plays an important role in understanding the function of genes and in constructing novel engineering bacteria according to requirement. DNA manipulation involves modifying the autologous genes and expressing the heterogenous genes. Two alternative approaches, using electroporation linear DNA or recombinant suicide plasmid, allow a wide variety of DNA manipulation. However, the over-expression of the desired gene is generally executed via plasmid-mediation. The current review summarizes the common strategies used for genetically modifying E. coli and C. glutamicum genomes, and discusses the technical problem of multi-layered DNA manipulation. Strategies for gene over-expression via integrating into genome are proposed. This review is intended to be an accessible introduction to DNA manipulation within the bacterial genome for novices and a source of the latest experimental information for experienced investigators.

Qualitative Analysis and Approximate Damped Oscillatory Solutions for a Kind of Nonlinear Dispersive-dissipative Equation

This paper makes qualitative analysis to the bounded traveling wave solutions for a kind of nonlinear dispersive-dissipative equation, and considers its solving problem. The relation is investigated between behavior of its solution and the dissipation coefficient. Further, all approximate damped oscillatory solutions when dissipation coefficient is small are presented by utilizing the method of undetermined coefficients according to the theory of rotated vector field in planar dynamical systems. Finally, error estimate is given by establishing the integral equation which reflects the relation between approximate and exact damped oscillatory solutions applying the idea of homogenization principle.

Orbital Stability of Solitary Waves of Compound KdV-type Equation

In this paper, we study the orbital stability of solitary waves of compound KdV-type equation in the form of ut ＋ auPux ＋ bu2pux ＋ Uzzz = 0 （b 〉 0, p 〉 0）. Our results imply that orbital stability of solitary waves is affected not only by the highest-order nonlinear term bu2pux, but also the nonlinear term auPux. For the case of b 〉 0 and 0 〈 p ≤ 2, we obtain that the positive solitary wave Ul（X - ct） is stable when a 〉 0, while that unstable when a 〈 0. The stability for negative solitary wave u2（x - ct） is on the contrary. In particular, we point that the nonlinear term with coefficient a makes contributes to the stability of the solitary waves when p= 2 and a〉0.

Exact Solitary-wave Solutions and Periodic Wave Solutions for Generalized Modified Boussinesq Equation and the Effect of Wave Velocity on Wave Shape

By means of the undetermined assumption method, we obtain some new exact solitary-wave solutions with hyperbolic secant function fractional form and periodic wave solutions with cosine function form for the generalized modified Boussinesq equation. We also discuss the boundedness of these solutions. More over, we study the correlative characteristic of the solitary-wave solutions and the periodic wave solutions along with the travelling wave velocity＇s variation.