Search

Cirrhosis caused by viral and alcoholic hepatitis is an essential cause of portal hypertension (PHT). The incidence of PHT complication is directly proportional to portal venous pressure (PVP), and the clinical research of PVP and its hemodynamic indexes is of great significance for deciding the treatment strategy of PHT. Various techniques are currently being developed to decrease portal pressure but hemodynamic side effects may occur. In this article, the hemodynamic indexes of cirrhotic PHT patients were studied to explore the correlation between the index and PVP and to evaluate the clinical value of Doppler ultrasound in measuring PVP in patients with PHT. This was achieved by selecting 90 cirrhotic PHT patients who underwent transjugular intrahepatic portosystemic shunt in our hospital from June 2015 to September 2019. Fifty healthy people who had a physical examination in the hospital in the same period were selected as the control group. The liver hemodynamic parameters of two groups were measured by Doppler ultrasound, and the cirrhotic PHT patients were graded by the Child–Pugh grading method to evaluate the liver function and measure the PVP value. The results showed that both the central portal vein velocity (PVV) and splenic vein velocity (SVV) of the PHT group were lower than those of the control group. Also, the portal vein diameter (PVD), portal venous flow and splenic vein diameter (SVD) were higher than those of the control group (all Ps < 0.05). Among liver function graded PHT patients, the PVD, PVV, SVD and SVV were significantly different (all Ps < 0.05). Furthermore, the PVP of patients with liver function grades A, B and C was 38.9 ± 1.4, 40.6 ± 5.1 and 42.5 ± 4.8 cmH2O, respectively, with a significant difference. It can be concluded from this study that Doppler ultrasound can be used as a tool for clinical assessment of PHT in cirrhosis patients. Doppler ultrasound showed a good prospect in noninvasive detection of PHT in cirrhosis; however, this technique needs application on large sample population study to validate the results.

The topology management classifiers consist of several methods, such as the typical clustering-based method excelled in wireless network partitioning. However, most algorithms appear load unbalanced in the application of irregular network, resulting “energy hot zone” phenomenon. This paper proposes an improved intelligent clustering algorithm and applies it to the complex water system environment. Firstly, we build a new energy consumption model for wireless transmission network, and design a genetic clustering strategy via the minimum energy consumption principle. Secondly, we introduce the P matrix coding approach considering the search scale, so as to avoid the squared increasing relationship between the searching space and the data calculation. Thirdly, we employ adaptive genetic operator to enhance the directivity of the searching space, and utilize a fuzzy modified operator to enhance the accuracy of the cluster head selection, which may ensure the iterative efficiency. Through numerical simulations, empirical results show better performance than traditional methods in load balancing and clustering efficiency, which can effectively improve the network convergence speed and extend the network lifetime.

Nanoscale drug delivery system (NDDS) with slow premature drug release (PDR) while ensuring burst intracellular drug release (BIDR) is becoming a hot point in NDDS-based nanomedicine. Here we used clathrin to modify a solid lipid nanoparticle (SLN)-based NDDS of salinomycin (SLN-SAL) to prepare NDDS with reduced PDR while ensuring BIDR. Drug-release-kinetic experiments revealed that clathrin modified SLN-SAL (CMSLN-SAL) reduced PDR while ensured BIDR of its prototype NDDS, SLN-SAL. Mechanism experiments revealed that clathrin modification reduced PDR of SLN-SAL through increasing the mechanical strength of SLN-SAL and ensured BIDR of SLN-SAL through lipid membrane fusion after its clathrin shell was de-polymerized by a cytoplasm enzyme, HSC70. In addition, CMSLN-SAL had significantly higher intracellular uptake and stronger inhibitive effects on cancer cells than that of SLN-SAL. These results demonstrated that clathrin modification is an effective way to reduce PDR while ensuring BIDR and increasing the anticancer effects of SLN-based NDDS.

Purpose Gastric cancer stem cells (CSCs) are important for the initiation, growth, recurrence, and metastasis of gastric cancer, due to their chemo-resistance and indefinite proliferation. Herein, to eliminate gastric CSCs, we developed novel CSC-targeting glioma-associated oncogene homolog 1 (Gli1) small interfering RNA (siRNA) nanoparticles that are specifically guided by a di-stearoyl-phosphatidyl-ethanolamine- hyaluronic-acid (DSPE-HA) single-point conjugate, as an intrinsic ligand of the CD44 receptor. We refer to these as targeting Gli1 siRNA nanoparticles. Methods We used the reductive amination reaction method for attaching amine groups of DSPE to aldehydic group of hyaluronic acid (HA) at the reducing end, to synthesize the DSPE-HA single-point conjugate. Next, targeting Gli1 siRNA nanoparticles were prepared using the layer-by-layer assembly method. We characterized the stem cellular features of targeting Gli1 siRNA nanoparticles, including their targeting efficiency, self-renewal capacity, the migration and invasion capacity of gastric CSCs, and the penetration ability of 3D tumor spheroids. Next, we evaluated the therapeutic efficacy of the targeting Gli1 siRNA nanoparticles by using in vivo relapsed tumor models of gastric CSCs. Results Compared with the multipoint conjugates, DSPE-HA single-point conjugates on the surface of nanoparticles showed significantly higher binding affinities with CD44. The targeting Gli1 siRNA nanoparticles significantly decreased Gli1 protein expression, inhibited CSC tumor spheroid and colony formation, and suppressed cell migration and invasion. Furthermore, in vivo imaging demonstrated that targeting Gli1 siRNA nanoparticles accumulated in tumor tissues, showing significant antitumor recurrence efficacy in vivo. Conclusion In summary, our targeting Gli1 siRNA nanoparticles significantly inhibited CSC malignancy features by specifically blocking Hedgehog (Hh) signaling both in vitro and in vivo, suggesting that this novel siRNA delivery system that specifically eliminates gastric CSCs provides a promising targeted therapeutic strategy for gastric cancer treatment.

Wireless weak-connected network (WWN) is a special self-organizing network, which can self-organize in an unstructured style and communicate with each other without infrastructure support. In this network, the link connection is weak and the topology is dynamic, which limits the performance of routing tasks. In order to address this issue, a novel Physarum-inspired routing algorithm (P-iRA) is proposed based on the intelligence and adaptability of Physarum polycephalum. Firstly, we construct a link capacity model for WWN via mapping the Physarum polycephalum network. Then, we design a next-hop selection strategy to obtain an optimal forwarding node in candidate set. Finally, we present a stochastic route strategy to achieve data transmission by virtue of finding the best routing path. Simulation results demonstrate that P-iRA improves approximately 47%, 34%, 56%, 20%, and 8% compared with Direct Delivery, Epidemic, First Contact, MaxProp, and Spray And Wait, respectively.

Target assignment for unmanned aerial vehicle (UAV) swarm has been a research hotspot in academic and industry communities. The current methods mainly focus on multiple targets assignment in planes or few targets assignment in solids. However, they ignore three-dimensional scenarios for UAV swarm and multiple targets characteristics for assignment problem. To solve these issues, we propose a multi-target intelligent assignment model. Firstly, we introduce damage cost and time cost to evaluate the system performance of swarm and time performance in three-dimensional scenarios. Then, we design a bio-inspired swarm intelligence optimization algorithm to find the optimal multiple targets assignment and to balance the two costs and multiple constraints simultaneously. This algorithm regards UAVs as several parallel biological sub-populations, which adopts the multi-layered optimization strategy to select the suitable assignment sequence. The simulation results demonstrate that the proposed method is effective for multi-target assignment in three-dimensional scenarios.

Folic acid (FA)-γ cyclodextrin (γ CD)-C60 was synthesized in this study as a carrier for tumor-targeted drug delivery to enhance the anticancer effect of carboplatin (CBP). FA-γ CD and C60-CBP were prepared and C60-CBP was then entrapped into FA-γ CD through host-guest effect. FA-γ CD-C60 significantly increased the intracellular uptake and release of CBP, thereby providing higher cytotoxicity against the HeLa cells with high expression of folate receptor (FR). In vivo experiments revealed that FA-γ CD-C60-CBP had more significant anticancer effects than CBP alone, showing no obvious toxic effects on zebrafish at concentration as high as 500 μg/mL. These results suggest that FA-γ CD-C60 may provide an effective strategy for administration of antineoplastics, with great promise in future targeted therapy for cancers.

The Xi’an Proton Application Facility (XiPAF) is a facility dedicated to the experimental simulation of the space radiation environment. The facility uses a compact synchrotron as its final-stage accelerator. The synchrotron can accelerate a proton beam from 7 to $$230\,\hbox {MeV}$$ . Physical design results show that the radio frequency (RF) acceleration system should work in the frequency range of $$1{-}6\,\hbox {MHz}$$ and provide a maximum voltage of $$>800\,\hbox {V}$$ . To dilute the strong space charge effect during the injection period, we also aim to achieve multiharmonic acceleration. A compact RF acceleration system loaded with magnetic alloy cores has been designed and developed to fulfill these requirements. The preliminary test results show that the system can work normally with a gap voltage of $$800\,\hbox {V}$$ . With a further RF power upgrade, the voltage can be improved to $$>1.2\,\hbox {kV}$$ .

Shuang Jiang,1,2,* Xiaobo Wang,2,* Zhiran Zhang,2 Lan Sun,3 Yunzhu Pu,3 Hongjuan Yao,3 Jingcao Li,3 Yan Liu,3 Yingge Zhang,3 Weijing Zhang1,4 1Department of Lymphoma, Affiliated Hospital of the Military Medical Academy of Sciences, Beijing, 2Department of Pharmacy, 210th Hospital of the People’s Liberation Army, Dalian, 3Key Laboratory of Nanopharmacology and Nanotoxicology, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 4Department of Lymphoma, Beijing Shijitan Hospital of Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: A monoclonal antibody targeted nanoscale drug delivery system (NDDS) for chemotherapy was evaluated in CD20-positive Raji cells in vitro. Nanoparticles were formed by the assembly of an amphiphilic polymer consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxypolyethyleneglycol-2000 (DSPE-PEG2000). Active carbon nanoparticles (ACNP) were conjugated to the chemotherapeutic agent, doxorubicin (DOX), and the nanoliposome carrier, DSPE-PEG2000 and DSPE-PEG2000-NH2 conjugated to the human anti-CD20 monoclonal antibody that targets B-lymphocytes. This monoclonal antibody targeted nanoparticle delivery system for chemotherapy formed the active NDDS complex, ACNP-DOX-DSPE-PEG2000-anti-CD20. This active NDDS was spherical in morphology and had good dispersion in the culture medium. When compared with the effects on CD20-negative YTS cells derived from natural killer/T-cell lymphoma, the active NDDS, ACNP-DOX-DSPE-PEG2000-anti-CD20, demonstrated DOX delivery to CD20-positive Raji cells derived from Burkitt’s lymphoma (B cell lymphoma), resulting in increased cell killing in vitro. The intracellular targeting efficiency of the ACNP-DOX-DSPE-PEG2000-anti-CD20 complex was assessed by confocal laser microscopy and flow cytometry. The findings of this in vitro study have shown that the DSPE-PEG2000 polymeric liposome is an effective nanocarrier of both a monoclonal antibody and a chemotherapy agent and can be used to target chemotherapy to specific cells, in this case to CD20-positive B-cells. Future developments in this form of targeted therapy will depend on the development of monoclonal antibodies that are specific for malignant cells, including antibodies that can distinguish between lymphoma cells and normal lymphocyte subsets. Keywords: CD20, active carbon nanoparticles, doxorubicin, nanoscale drug delivery, targeted therapy, DSPE-NH2-anti-CD20 conjugate

A new RIB project, Beijing Radioactive Ion-beam Facility (BRIF), has been started at CIAE since 2004. For this project, a 100 MeV high intensity compact cyclotron, CYCIAE-100, is selected as the driving accelerator for radioactive ion beam production. The cyclotron will provide the proton beam of 75–100 MeV with an intensity of 200–500 μA. The features of the cyclotron have already been described in several papers published elsewhere. In this paper the beam dynamics study is reviewed systematically. The basic parameters and numerical calculations results on the static orbit and accelerated orbit are given. The space charge effects, including the mutual interaction of neighboring multiple bunches in the radial direction, are studied with OPAL-CYCL code, and the current limit determined by space charge effects for this machine is predicted by fully 3D simulation.

CYCIAE-100, a 100 MeV H− cyclotron under construction at China Institute of Atomic Energy (CIAE), is an AVF compact cyclotron. With energy above 70 MeV, the straight-edge sector magnet, instead of the spiral one normally used for AVF cyclotrons in this case, is still used to simplify the engineering procedures. The vertical focusing is likely not strong enough at the outer region and the Walkinshaw resonance may occur, if either the permeability decreasing tolerance in large scale pure iron castings and forgings, or the fabrication tolerance during the magnet construction, are seriously excessive. Theoretical investigation and numerical simulation results presented in this paper show that this kind of risk could be avoided by using a set of specially designed asymmetrical shimming bars between the pole edge and dummy Dee of the RF cavity at the outer region. In this way, the vertical focusing at outer radius region will increase substantially. This investigation provides a protective measure for the main magnet construction of CYCIAE-100.

For the production of intense protons and radioactive ion beam(RIB) used in fundamental and applied research, the Beijing radioactive ion-beam facility (BRIF) was started at China Institute of Atomic Energy (CIAE) in 2004. A 100 MeV H − cyclotron, CYCIAE-100, is designed as the driving accelerator to provide proton consistent beams from 75 to100 MeV with the beam intensity up to 200 μA. The cyclotron contains seven beam lines in total for different experimental applications. The transfer matrix from the stripper to the extracted-switch-magnet is calculated in the design. Based on this matrix and the beam parameter on the stripper, the beam optics simulation is carried out from the stripper to the experimental terminal. Other aspects pertaining to the beamline design, including the arrangement of the elements and magnets are also illustrated in this paper.

The beam dynamics behaviour in the compact cyclotron central region is investigated. The design study for central region, including the spiral inflector, Dee tip, shield and posts, for three cyclotrons at CIAE will be described in this paper. The code development by CIAE and the UNIX based codes developed by TRIUMF were implemented on WINDOWS/PC by CIAE for the spiral inflector and central region design will be given too.

A 14 MeV high intensity compact cyclotron, CYCIAE-14, was built at China Institute of Atomic Energy (CIAE). An injection system based on the external H− ion source was used on CYCIAE-14 so as to provide high intensity beam, while most positron emission tomography cyclotrons adopt internal ion source. A beam intensity of 100 μA/14 MeV was extracted from the cyclotron with a small multi-cusp H− ion source (CIAE-CH-I type) and a short injection line, which the H− ion source of 3 mA/25 keV H− beam with emittance of 0.3π mm mrad and the injection line of with only 1.2 m from the extraction of ion source to the medial plane of the cyclotron. To increase the extracted beam intensity of the cyclotron, a new ion source (CIAE-CH-II type) of 9.1 mA was used, with maximum of 500 μA was achieved from the cyclotron. The design and test results of the ion source and injection line optimized for high intensity acceleration will be given in this paper.

In this thesis the chromatography on Sephadex G-100 was used to purify the purple sweet potato polysaccharide (PPSP-1) which had been isolated by DEAE-Cellulose 52 column. To get the best purification effect, the several elution conditions were researched in tests. The results suggested that the purification effect of Sephadex G-100 was best when eluted with 5.85g.L-1 NaCl after loading with 1mL sample then collected 2mL eluates each tube; the small, middle and large molecular weight range polysaccharides (PPSP-1-1-1, PPSP-1-1-2 and PPSP-1-1-3 respectively) got under the best purification effect did't contain the protein and polypeptide; the infrared spectra presented that the PPSP-1-1-2 and the PPSP-1-1-3 configurations of the end group anomeric carbon were both α-type, their ring structures were both furanoid type; the molecular weights of polysaccharide under the first three peaks were calculated roughly by the method of gel chromatography and they were about 129,909Da, 107,354Da and 88,715Da respectively.

The construction of a 100-MeV high-intensity cyclotron, from which proton beam will be extracted through stripping to several proton beam lines for different users, has been completed at China Institute of Atomic Energy. Given that it is the H-ions that are to be accelerated in the machine, the peak field is only 1.35 T. To simplify the fabrication, the pole adopts straight sector instead of the spiral one. Meanwhile, vertical focusing should be sufficiently high to obtain high-current proton beam. All these demands make it particularly difficult for the design and fabrication of the main magnet, which is heavy in weight and challenging to meet precision requirement in fabrication. In the process, we have developed a high-performance parallel computation PIC code for beam dynamics of high-current cyclotrons and for FFAGs, which can be used for beam dynamic simulation at a very precise level. The result is then applied to guide the design, fabrication, installation, magnetic mapping, and shimming of the 416-ton main magnet with a precision requirement up to 0.05 mm. Another challenge is due to the deformations of the magnet without/with the vacuum. The whole map measured in the vacuum has to be completed in such a big machine for the first time in the world. The result shows that all requirements, including the isochronous field, vertical focusing, and imperfection fields, have been satisfied properly. The first beam and the stable beam for an 8-h commissioning test had been achieved on July 4 and July 25, 2014, respectively.

Recently, a new H- source and test stand was developed at CIAE. The design of this new source is based on the experience on our previous 10-15 mA H(-) ion source and the source at TRIUMF. Major efforts include the study of the virtual filter magnetic field, confining magnetic field, filament shape and location, the vacuum improvement on the extracting area, the extraction optics, new control and interlock system of the power supplies. More than 15 mA of H-beam was obtained for 36 h with stability of +/-0.5%. The normalized emittance of 0.48pi mm mrad (4 rms normalized emittance) were measured with approximately 8 mA dc beam. Further experimental studies are proceeding in an effort to reach 20 mA with reasonable emittance at this moment. More study plans are conducted, e.g., building a longer source body and using cesium injection to get better emittance, which will be presented as a separate paper at this conference.

At the China Institute of Atomic Energy, a central region model cyclotron has been constructed, which is dedicated for various experimental verifications to study beam properties. The design features of the ion source and injection line have already been described in other papers. We shall report here the results of the initial beam tests. A wire scanner is employed in the injection line to measure beam transverse sizes and these data can be used to fit the phase plane parameters after the ion source. Based on the beam tests results, the ion source built in 2003 has been improved recently. The improvement is mainly due to the repair of the multicusp field. From the ion source to the exit of the inflector, a transmission efficiency of 93% has been obtained for a continuous and low current input beam. It is also described here the experimental arrangement and the results.

At CIAE, a 100 MeV H(-) cyclotron (CYCIAE-100) is under design and construction. A central region model (CRM) cyclotron was built for various experimental verifications for the CYCIAE-100 project and for research and development of high current injection to accelerate milliampere H(-) beam. The H(-) multicusp source built in 2003 has been improved recently to make the source operation more stable. A new injection line for axial low energy high current injection has been designed and constructed for the CRM cyclotron.

The way of matching the beam from an external ion source to the central region of the cyclotron CYCIAE-100 is presented in this article. The transverse acceptances of the central region were calculated, which provided the matching ellipse parameter requirements to the injection transport optics design. The optics of the injection line was simulated using TRANSOPTR, which allowed space charge effect calculation, and neutralization was taken into account.

A comprehensive test stand for high-intensity cyclotron development, a 10 MeV 430 μA cyclotron, has been successfully constructed at China Institute of Atomic Energy (CIAE) for the experimental verification of the viability of a 100 MeV high-intensity cyclotron (CYCIAE-100) being constructed at CIAE. The verification includes the overall design technology, detail design and engineering technology for the crucial parts of the machine, e.g. main magnet and beam diagnostics. It will also pave the way for future enhancement of the beam intensity. The test stand consists of a H− ion source, axial injection system, central region, main magnet and coil, RF resonator, stripping extraction, and auxiliary systems, which include the RF power amplifier, high voltage and DC power supplies, electric apparatus, beam diagnostics, control, vacuum, water cooling, pneumatic system, and safety interlock. This paper presents the work regarding the design and sub-system development of the test sand, and the results of the beam commissioning of the machine.