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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.

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.

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

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.

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.