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Update on acute myeloid leukemia stem cells:New discoveries and therapeutic opportunities

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World Journal of Stem Cells 2016年第10期8卷 316-331页

作者： Maximilian Stahl Tae Kon Kim Amer M Zeidan section of Hematology Department of Internal MedicineYale School of Medicine

The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use of the key features shared with normal hematopoietic stem cells(HSCs) such as the capacity of self-renewal and the ability to initiate and sustain growth of progenitors in vivo. Significant progress has also been made in identifying the phenotype and signaling pathways specific for LSCs. Therapeutically, a multitude of drugs targeting LSCs are in different phases of preclinical and clinical development. This review focuses on recent discoveries which have advanced our understanding of LSC biology and provided rational targets for development of novel therapeutic agents. One of the major challenges is how to target the selfrenewal pathways of LSCs without affecting normal HSCs significantly therefore providing an acceptable therapeutic window. Important issues pertinent to the successful design and conduct of clinical trials evaluating drugs targeting LSCs will be discussed as well.

关键词： Leukemia stem cells Cancer stem cells Acute myeloid leukemia Stem cell niche Xenotransplantation Plerixafor NF-κ B C-X-C chemokine receptor type 4

Image guided percutaneous gastrostomy catheter placement: How we do it safely and efficiently

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World Journal of Gastroenterology 2020年第4期26卷 383-392页

作者： Sasan Partovi Xin Li Eunice Moon Dustin Thompson section of Interventional Radiology Imaging Institute Cleveland Clinic Foundation

Gastrostomy tube is an effective and safe long-term feeding access that is welltolerated by *** typical placement routes include surgical,endoscopic and interventional radiologic *** particular,percutaneous interventional radiologic gastrostomy(PIRG)has increasingly become the preferred method of choice in many *** many PIRG techniques have been developed since the 1980s,there is still a paucity of evidence supporting the choice of a most-optimal PIRG ***,there is a large variation in institutional approach to *** are a large,quaternary academic institution with an extensive experience in ***,we aim to present the“push”PIRG technique utilized in our institution,to review the current literature,to discuss the optimal choice of PIRG technique and to generate further interests in comparison studies.

关键词： Percutaneous interventional radiologic gastrostomy Institutional approach Push technique

Noninvasive molecular analysis of Helicobacter pylori : Is it time for tailored first-line therapy?

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World Journal of Gastroenterology 2017年第14期23卷 2453-2458页

作者： Enzo Ierardi Floriana Giorgio Andrea Iannone Giuseppe Losurdo Mariabeatrice Principi Michele Barone Antonio Pisani Alfredo Di Leo Gastroenterology section Department of Emergency and Organ Transplantation University of Bari

The main problem of Helicobacter pylori(H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction(PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin su

关键词： Helicobacter pylori Antibiotic resistance Noninvasive molecular test Tailored therapy Stool

Frequency-domain generelaized singular peruturbation method for relative error model order reduction

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控制理论与应用（英文版） 2009年第1期7卷 57-62页

作者： Hamid Reza SHAKER section for Automation and Control Institute for Electronic SystemsAalborg University

A new mixed method for relative error model order reduction is proposed. In the proposed method the frequency domain balanced stochastic truncation method is improved by applying the generalized singular perturbation method to the frequency domain balanced system in the reduction procedure. The frequency domain balanced stochastic truncation method, which was proposed in [15] and [17] by the author, is based on two recently developed methods, namely frequency domain balanced truncation within a desired frequency bound and inner-outer factorization techniques. The proposed method in ttiis paper is a carry over of the frequency-domain balanced stochastic truncation and is of interest for practical model order reduction because in this context it shows to keep the accuracy of the approximation as high as possible without sacrificing the computational efficiency and important system properties. It is shown that some important properties of the frequency domain stochastic balanced reduction technique are extended to the proposed reduction method by using the concept and properties of the reciprocal systems. Numerical results show the accuracy, simplicity and flexibility enhancement of the method.

关键词： Large-scale systems Model reduction Balanced realization Frequency-domain Grammian

Human sperm immobilization effect of Carica papaya seed extracts: an in vitro study

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Asian Journal of Andrology 2000年第2期2卷 103-109页

作者： Nirmal K Lohiya Lalit K Kothari B Manivannan Pradyumna K Mishra Neelam Pathak Reproductive Physiology section Department of Zoology University of Rajasthan Jaipur-302 004 India Reproductive Medicine Clinic 50 Gem Enclave Malviya Nagar Jaipur IndiaReproductive Physiology Section Department of Zoology University of Rajasthan Jaipur-302 004 India Reproductive Physiology Section Department of Zoology University of Rajasthan Jaipur-302 004 India Reproductive Physiology Section Department of Zoology University of Rajasthan Jaipur-302 004 India

Aim: To examine if the seed extracts of Carica papaya, which showed anfispermatogenic/sperm immobilizationproperties in animal models, could cause human sperm immobilization in vitro. Methods: Chloroform extract, ben-zene chromatographic fraction of the chloroform extract, its methanol and ethyl acetate sub-fractions and the isolatedcompounds from the sub-fractions i. e., ECP 1 & 2 and MCP 1 & 2, of the seeds of Carica papaya were used at con-centrations of 0.1%, 0.5%, 1% and 2%. Sperm motility was assessed immediately after addition of extracts and ev-ery 5 minutes thereafter for 30 minutes. Results: There were dose-dependent spermicidal effects showing an instantfall in the sperm motility to less than 20% at 2% concentration. Isolated compounds ECP 1 & 2 were more effective in-ducing a motility of less than 10%. Many of the spermatozoa became vibratory on the spot. Total inhibition of motilitywas observed within 20-25 rain at all concentrations of all products. Scanning and transmission electron microscopyrevealed deleterious changes in the plasma membrane of the head and mid-piece of spermatozoa. Sperm viability testand the number of abnormal spermatozoa after completion of incubation suggested that the spermatozoa were *** effects were spermicidal but not spermiostatic as revealed by the sperm revival test. Conclusion: The results re-veal spermicidal activity in vitro of the seed extracts of Carica papaya.

关键词： human sperm sperm immobilization spermicidal agents Carica papaya

Contraceptive effect of Curcuma longa (L.) in male albino rat

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Asian Journal of Andrology 2004年第1期6卷 71-74页

作者： Purohit Ashok Bhagat Meenakshi Reproductive Physiology section Department of Zoology JNV University Jodhpur (Raj.) 342005 IndiaReproductive Physiology Section Department of Zoology JNV University Jodhpur (Raj.) 342005 India

Aim: To study the contraceptive effect of the crude extracts of Curcuma longa in male albino rats. Methods: Rats were fed orally with Curcuma longa aqueous and 70 % alcoholic extract for 60 days (500 mg·kg-1· day-1). Results: A reduction in sperm motility and density was observed in both the treated groups. Conclusion: Curcuma longa may have affected the androgen synthesis either by inhibiting the Leydig cell function or the hypo-thalamus pituitary axis and as a result, spermatogenesis is arrested.

关键词： Leydig cells Curcuma longa seminiferous tubules antiandrogens spermatozoa male contraception

Numerical investigation on the flow structures in a narrow confined channel with staggered jet array arrangement

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Chinese Journal of Aeronautics 2015年第6期28卷 1616-1628页

作者： Liu Haiyong Liu Cunliang Wu Wenming section of Engine and Energy Xi'an High-Tech Institute School of Power and Engine Northwestern Polytechnical University

A series of numerical analyses have been performed to investigate the flow structures in a narrow confined channel with 12 staggered circular impingement holes and one bigger exit hole. The flow enters the channel through the impingement holes and exits through the far end outlet. The flow fields corresponding to two jet Reynolds numbers （25000 and 65000） and three channel con- figurations with different ratios of the channel height to the impingement hole diameter （Zr 1, 3, 5） are analyzed by solving the Reynolds averaged Navier-Stokes equations with the realizable k-e turbulence model. Detailed flow field information including the secondary flow, the interaction between the jets and the cross flow, and flow distribution along the channel has been obtained. Comparisons between the numerical and experimental results of the flow fields at the four planes along the channel are performed to validate the numerical method. The calculated impingement pattern, high velocity flow distribution, low velocity separation region and vortices are in good agreement with the experimental data, implying the validity and effectiveness of the employed numerical approach for analyzing relevant flow field.

关键词： Confined channel Cross flow Flow structure Impingement coolingTurbulence model

Modeling and analysis of mover gaps in tubular moving-magnet linear oscillating motors

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Chinese Journal of Aeronautics 2018年第5期31卷 927-940页

作者： Xuesong LUO Chao ZHANG Shaoping WANG Enrico ZIO Xingjian WANG School of Automation Science and Electrical Engineering Beihang University Energy Department-Nuclear section Polytechnic of Milan

A tubular moving-magnet linear oscillating motor（TMMLOM） has merits of high efficiency and excellent dynamic capability. To enhance the thrust performance, quasi-Halbach permanent magnet（PM） arrays are arranged on its mover in the application of a linear electro-hydrostatic actuator in more electric aircraft. The arrays are assembled by several individual segments, which lead to gaps between them inevitably. To investigate the effects of the gaps on the radial magnetic flux density and the machine thrust in this paper, an analytical model is built considering both axial and radial gaps. The model is validated by finite element simulations and experimental *** of the magnetic flux are described in condition of different sizes of radial and axial gaps. Besides, the output force is also discussed in normal and end windings. Finally, the model has demonstrated that both kinds of gaps have a negative effect on the thrust, and the linear motor is more sensitive to radial ones.

关键词： Air-gap flux density Linear motor Mover gaps Quasi-Halbach array Thrust output Tubular moving-magnet linear oscillating motor(TMMLOM)

From chronic liver disorders to hepatocellular carcinoma: Molecular and genetic pathways

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World Journal of Gastrointestinal Oncology 2010年第6期2卷 259-264页

作者： Enzo Ierardi Rosa Rosania Mariangela Zotti Floriana Giorgio Simonetta Prencipe Nicola Della Valle Vincenzo De Francesco Carmine Panella section of Gastroenterology Department of Medical Sciences University of Foggia

Hepatocarcinogenesis is a process attributed to progressive genomic changes that alter the hepatocellular phenotype producing cellular intermediates that evolve into hepatocellular carcinoma (HCC). During the preneoplastic phase, the liver is often the site of chronic hepatitis and/or cirrhosis, and these conditions induce liver regeneration with accelerated hepatocyte cycling in an organ that is otherwise proliferatively at rest. Hepatocyte regeneration is accelerated by upregulation of mitogenic pathways involving molecular and genetic mechanisms. Hepatic growth factors, inhibitors and triggers may also play a role. This process leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that have telomerase reexpression, microsatellite instability, and occasionally structural aberrations in genes and chromosomes. Development of dysplastic hepatocytes in foci and nodules and the emergence of HCC are associated with the accumulation of irreversible structural alterations in genes and chromosomes even if the genomic basis of the malignant phenotype is largely heterogeneous. Therefore, a malignant hepatocyte phenotype may be produced by changes in genes acting through different regulatory pathways, thus producing several molecular variants of HCC. On these bases, a key point for future research will be to determine whether the deletions are specific, due to particular loci in the minimally deleted regions of affected chromosome arms, or whether they are nonspecific with loss of large portions of chromosomes or entire chromosome arms leading to passive deletion of loci. The final aim is the possibility of identifying a step where carcinogenetic processes could be terminated.

关键词： Hepatocarcinoma Chronic liver disorders Genetic pathways Molecular pathways Hepatic growth factors Augmenter liver regeneration