Chemotherapy and target therapy for hepatocellular carcinoma:New advances and challenges

Primary liver cancer is one of the commonest causes of death.Hepatocellular carcinoma(HCC) accounts for 90% of primary liver cancers.For patients with unresectable or metastatic HCC,conventional chemotherapy is of limited or no benefit.Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit,leading to an era of targeted agents.Many clinical trials of targeted drugs have been carried out with many more in progress.Some drugs like PTK787 showed potential benefits in the treatment of HCC.Despite these promising breakthroughs,patients with HCC still have a dismal prognosis.Recently,both a phase Ⅲ trial of everolimus and a phase Ⅱ clinical trial of trebananib failed to demonstrate effective antitumor activity in advanced HCC.Sorafenib still plays a pivotal role in advanced HCC,leading to further explorations to exert its maximum efficacy.Combinations targeted with chemotherapy or transarterial chemoembolization is now being tested and might bring about advances.New targeted agents such as mammalian target of rapamycin inhibitors are under investigation,as well as further exploration of the mechanism of hepatocarcinogenesis.

Integrin-linked kinase overexpression promotes epithelial-mesenchymal transition via nuclear factor-κB signaling in colorectal cancer cells

AIM: To investigate the effect of integrin-linked kinase(ILK) on proliferation, metastasis, and invasion of the colorectal cancer cell line SW480. METHODS: In this study, the colorectal cancer cell line SW480 was stably transfected with ILK plasmids, and small interfering RNA(si RNA) was used to knockdown expression of nuclear factor(NF)-κB/p65. Methylthiazole tetrazolium(MTT) assay was performed to measure proliferation, and the wound healing migration assay and matrigel invasion assay were used to test the metastasis and invasion ability of SW480 cells. To explore the epithelial-mesenchymal transition(EMT) process, embryonic development, and the invasion and metastasis of tumors, the protein level of E-cadherin, vimentin, snail, and slug was detected by western blot. Immunofluorescence was also used to detect E-cadherin expression. Western blot was used to determine the level of phosphorylated-inhibitor of kappa B(IκB)a, inhibitor of gamma B(IγB)a, and nuclear factor kappa B(NF-κB) expressions and toexplore the ILK signaling pathway. RESULTS: Western blot results revealed that ILK expression significantly increased when ILK was overexpressed in SW480 cells(P < 0.05). Proliferation, metastasis, and invasion ability were improved in the vector-ILK group compared to the vector group(P < 0.05). Immunofluorescence results revealed that E-cadherin fluorescence intensity decreased after ILK was overexpressed(P < 0.05). Western blot results revealed that the protein expression of E-cadherin was reduced, while vimentin, snail, and slug were upregulated when ILK was overexpressed in SW480 cells(P < 0.05). In order to determine the role of the NF-κB signaling pathway in ILK overexpression promoted EMT occurrence, we overexpressed ILK in SW480 cells and found that levels of NF-κB/p65 and cytoplasmic phosphorylated-IκBa were increased and that cytoplasmic IкBa levels were decreased compared to the control group(P < 0.05). Furthermore, NF-κB/p65 knockout revealed that E-cadherin was increased in the overexpressed ILK group. CONCLUSION: ILK overexpression improved the proliferation, metastasis, and invasion ability of SW480 cells, and this effect may be mediated by the NF-κB signaling pathway.

THE STEPS FORWARD OF GIS IN CHINA

Researches and applications of Geographic Information Systems (GIS) in China started in the early 1980s. In the early period, the development of GIS was mainly depended on the progress and applications of remote sensing, aerial photography, as well as computer aided design (CAD). In recent years, with the development of Global Positioning System(GPS) and Internet technology, GIS has being developed vigorously in the county. Looking ahead to the 21st century, a new era of “Digital Earth” and “Cyberspace” is coming, which will provide a great opportunity as well as a challenge to the China’s GIS circles.

基于高通量测序分析晚期肺癌患者肺部微生物多样性

背景与目的肺部微生物组与肺部疾病的发生密切相关,微生物可从多方面促进肿瘤的发生与发展。既往研究证实肺癌患者肺部微生物组较健康人发生了变化,但关于不同类型肺癌患者中肺部微生物组的微生物组成尚未明确。本研究旨在探讨不同组织学类型肺癌间的微生物组相关性及差异性。方法采用Illumina HiSeq高通量测序技术对晚期肺癌患者痰样本进行细菌V3-V4区的16S rDNA测序及生物信息学分析。结果经物种分类分析发现肺癌患者痰样本中以链球菌属、奈瑟氏菌属、普雷沃氏菌属为主。腺癌(adenocarcinoma,AD)组以链球菌属及奈瑟氏菌属为主,小细胞肺癌(small cell lung cancer,SCLC)组以奈瑟氏菌属为主,鳞状细胞癌(squamous cell carcinoma,SCC)组以链球菌属为主,混合型小细胞肺癌(combined small cell lung cancer,C-SCLC)组以链球菌属为主。结论不同组织学类型肺癌的肺部细菌微生物组结构及组成存在差异性,不同组织学类型肺癌间优势菌群有所不同,本研究丰富了肺癌肺部细菌微生物组学数据。

Vibration analysis of piezoelectric sandwich nanobeam with flexoelectricity based on nonlocal strain gradient theory

A nonlocal strain gradient theory(NSGT) accounts for not only the nongradient nonlocal elastic stress but also the nonlocality of higher-order strain gradients,which makes it benefit from both hardening and softening effects in small-scale structures.In this study, based on the NSGT, an analytical model for the vibration behavior of a piezoelectric sandwich nanobeam is developed with consideration of flexoelectricity. The sandwich nanobeam consists of two piezoelectric sheets and a non-piezoelectric core. The governing equation of vibration of the sandwich beam is obtained by the Hamiltonian principle. The natural vibration frequency of the nanobeam is calculated for the simply supported(SS) boundary, the clamped-clamped(CC) boundary, the clamped-free(CF)boundary, and the clamped-simply supported(CS) boundary. The effects of geometric dimensions, length scale parameters, nonlocal parameters, piezoelectric constants, as well as the flexoelectric constants are discussed. The results demonstrate that both the flexoelectric and piezoelectric constants enhance the vibration frequency of the nanobeam.The nonlocal stress decreases the natural vibration frequency, while the strain gradient increases the natural vibration frequency. The natural vibration frequency based on the NSGT can be increased or decreased, depending on the value of the nonlocal parameter to length scale parameter ratio.

Recurrent Patterns and Factors Involved in Node-negative Advanced Gastric Cancer

Objective： To investigate the recurrent patterns and factors involved in node-negative advanced gastric cancer after curative resection. Patients and Methods： Clinicopathological characteristics and prognostic outcomes of 310 patients who had lymph node-negative advanced gastric adenocarcinoma and received curative resection between 2002 and 2006 were retrospectively evaluated. Results： Among the 300 patients, 15 （5.0%） had locoregional recurrence, 5 （1.7%） had lymph node recurrence, 27 （9.0%） had peritoneal seeding recurrence, and 21 （7.0%） had hematogenous metastasis. Using multivariate analysis, we found that the maximum tumor diameter （P=0.014）, histological type （P=0.001） and Borrmann type （P=0.033） were independent factors predicting the locoregional recurrence. Lymph node recurrence was significantly affected by lymph node dissection （P=0.029） and lymphovascular invasion （P=0.004）. Clinicopathological factors predicting the peritoneal seeding recurrence were the depth of invasion （P=0.001） and Borrmann type （P=0.002）. In addition, lymphovascular invasion （P=0.013） and histological type （P=0.001） were significantly associated with hematogenous metastasis. Conclusion： Node-negative advanced gastric cancer has a high amount of peritoneal seeding and hematogenous metastasis.

川南地区ABO血型与不同病理类型肺癌的关系

目的探讨川南地区ABO血型与不同病理类型肺癌的关系。方法回顾性分析西南医科大学附属医院2017年8月—2020年12月收治的903例肺癌患者(肺癌组)的临床资料和ABO血型。根据病理类型将肺癌组分为小细胞肺癌组(n=154)和非小细胞肺癌组(n=749),后者再分为肺腺癌组(n=442)、肺鳞癌组(n=307)。选取该院同期1061例健康体检者为对照组。比较各肺癌组与对照组的ABO血型分布。结果肺鳞癌组的ABO血型分布为A型(31.9%)、B型(39.7%)、O型(21.2%)、AB型(7.2%),对照组的ABO血型分布为A型(32.2%)、B型(24.4%)、O型(35.7%)、AB型(7.6%),两组的血型构成比较,差异有统计学意义(P<0.001)。调整年龄、性别、吸烟史及饮酒史后,多因素Logistic回归分析显示:B型血患肺鳞癌的风险较O型血高(P<0.05),年龄<60岁患肺鳞癌风险较年龄≥60岁低(P<0.05),不吸烟者患肺鳞癌风险较吸烟者低(P<0.05)。小细胞肺癌组、肺腺癌组与对照组ABO血型构成比较,差异无统计学意义(P>0.05)。结论川南地区ABO血型与肺鳞癌的发生可能有相关性,与小细胞肺癌、肺腺癌无相关性。

JUNO sensitivity on proton decay p→νK^(+)searches

The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK^(+)mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification.Moreover,the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals.Based on these advantages,the detection efficiency for the proton decay via p→νK^(+)is 36.9%±4.9%with a background level of 0.2±0.05(syst)±0.2(stat)events after 10 years of data collection.The estimated sensitivity based on 200 kton-years of exposure is 9.6×1033 years,which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies.

Design and experimental study of the fertilizer applicator with vertical spiral fluted rollers

To improve the uniformity and accuracy of fertilizing amount for fertilizer applicators with spiral fluted roller,this paper experimentally studied the influence of major structural parameters on the fertilizing performance.Through two sets of orthogonal tests,it is found that the helix angle and installation angle of spiral fluted rollers are the main factors,which affect the uniformity of fertilizer discharge and the linear relationship between fertilizing amount and opening,respectively.Based on these findings,the experiment and analysis were carried out to determine the optimal helix angle and installation angle for the spiral fluted roller The experimental results of fertilizing performance show that:when the helix angle is 45°,it able to achieve satisfactory uniformity of fertilizer discharge and linear relationship between fertilizing amount and rotational speed;when the installation angle is 40°,it enhances the accuracy of fertilizer discharge with good linear relationship between fertilizing amount and opening.Compared with the fertilizing performance of traditional fertilizer applicators with horizontally installed straight fluted roller,in the aspect of uniformity,the optimized fertilizer applicators reduce the variation coefficient of fertilizing amount within 0.2 s at low speed(10-30 r/min)from 5.1%-52.5%to 4.2%-14.7%;in the aspect of accuracy;and increase the correlation coefficient square R2 between fertilizing amount and opening from 0.93-0.97 to no less than 0.996,and the regression intercept in the fitting equation is reduced from larger than 10.0 to less than 1.0.

Structural design and parameter determination for fluted-roller fertilizer applicator

The instability of the motion layer of fertilizer particle influences the precision and the accuracy of the amount of fertilizer application in the working process of fluted-roller fertilizer applicator.The characteristics of the motion layer were investigated,and a systematic scheme was proposed for designing the structures of fertilizer-filling cavity,fertilizer-filling surface and fertilizer-delivery cavity.The key parameters of the structure were studied by discrete element method.It was figured out that to ensure the smooth operation of fertilizer applicator,the fertilizer-filling angle was 105°,fertilizer-contact angle should be large than 100°,and the fertilizer-resistance angle should be smaller than 35°.Moreover,the stability of fertilizer motion morphology was investigated to verify the design.The results showed that when the roll rotational speed was larger than 120 deg/s,compared with the conventional design the CV of the amount of fertilizer application was reduced from 1.5%-3.5%to 0.5%-1.0%,and the accuracy of the fertilizer discharge was improved with the square of the correlation coefficient between the amount of fertilizer application and the roll rotational speed was larger than 0.999.It was deduced from the results that the precision and accuracy of the amount of fertilizer application are improved via eliminating the driving layer and enhancing the stable filling and conveying of the forced layer.

Design and experiment of vertical pneumatic fertilization system with spiral Geneva mechanism

In the traditional fertilization method,a large amount of fertilizer is applied,which causes congestion easily.It is not conducive to the sustainable development of agriculture.In this work,a vertical pneumatic fertilization system with a spiral Geneva mechanism was designed according to the operational requirements of variable-rate and smooth fertilization.The uniformity in discharging fertilizer with different spiral angles was simulated and analyzed by extended discrete element method(EDEM)based simulation software,from where the spiral angle of the fertilizer discharge wheel was determined to be 45°.The fertilization system includes a fertilizer apparatus with a spiral Geneva mechanism,whose optimal performance parameters were obtained from the bench experiment.The accuracy and uniformity of the fertilizer application system were taken as the evaluation indicators.The linear relationships of the discharged amount of fertilizer with the rotational speed and the opening of the fertilizer discharging wheel were verified by both static blowing fertilization and field experiments.The static blowing experimental results show that the discharged amount of fertilizer has a high linear correlation and accuracy with both the opening and rotational speed,and the highest correlation occurs with the rotational speed.The rotational speed and opening have significant effects on the discharged amount of fertilizer and the average coefficient of variation.The effect of the rotational speed was the most significant.According to the model obtained by multiple regression fittings,the optimal parameters were determined when the average coefficient of variation was small,the rotational speed was 15.9 r/min and the opening was 34.4 mm.Therefore,the purpose of precise fertilization can be achieved by adjusting the opening or rotational speed in a way to get the exact amount of fertilizer discharged as required by the corresponding crops.The field experiment showed that the variation coefficient of each fertilizer discharged decreases first and then increases with an increasing opening under different rotational speeds,which is consistent with the theoretical value.When the opening was 40 mm or 50 mm,the variation coefficient reached the minimum value,which is far less than the qualified index of 7.8%.In the static blowing experiment and the dynamic field experiment,the stability of the fertilizer discharging device can be significantly enhanced with the utilization of the pneumatic conveying fertilizer.This study can provide a theoretical reference for parameter selection and optimization of vertical spiral fertilization systems.

Unidirectional and stage-dependent roles of Notch1 in Wnt-responsive Lgr5+ cells during mouse inner ear development

Wnt and Notch signaling play crucial roles in the determination of the prosensory domain and in the differentiation of hair cells(HCs)and supporting cells during mouse inner ear development;however,the relationship between the two signaling pathways in the mouse cochlea remains largely unknown.Here,we investigated the interactions between Notch and Wnt signaling on the basis of the bidirectional regulation of Notch1 specifically in Wnt-responsive Lgr5+progenitors during different cochlear development stages.We found that the downregulation of Notch1 in Lgr5+cells from embryonic day(E)14.5 to E18.5 can drive the quiescent Lgr5+cells to re-enter the cell cycle and differentiate into extra HCs,whereas the upregulation of Notch1 expression did not affect the proliferation or differentiation of otic progenitor cells.No effect was observed on the upregulation or downregulation of Notch1 in Lgr5+cells from E10.5 to E14.5.We concluded that the roles of Notch1 in Wnt-responsive Lgr5+cells are unidirectional and stage dependent and Notch1 serves as a negative regulator for Lgr5+progenitor activation during cochlear differentiation.Our findings improved the understanding of the interactions between Notch and Wnt signaling in cochlear development.

Numerical simulation and experiment of grain motion in the conveying system of ratooning rice harvesting machine

The mixtures,grains,and residues in the ratooning rice harvesting machine need to be conveyed forward,backward,upward,and downward.Due to such operations,often accumulation and blockage take place at the intersection of a horizontal-vertical screw conveyor,resulting in low efficiency,high power consumption,and even grain damage.In this study,a CFD-DEM approach was applied to address the above problems.Firstly,a pneumatic conveying device was designed for ratooning rice,and then the motion of the rice grains and airflow field was analyzed in detail.The effects of different cross-sectional heights and lengths of the contraction section related to the mixing cavity were examined.Finally,the three-factor quadratic regression orthogonal rotational combination method was adopted in the experiment,and the fan velocity,filling coefficient,and speed of the horizontal screw conveyor were taken as test factors.The results showed that with the increasing cross-sectional height of the contraction section in the mixing cavity,the grain velocity decreased and the dispersity increased.With increasing length of the contraction section in the mixing cavity,the area of the high-speed airflow zone increased and the diffusion effect was enhanced.At the fan velocity of 2700 r/min,the filling coefficient was 0.41,the speed of the horizontal screw conveyor was 1173 r/min,and the outlet flow optimization index was the highest,which was 45.9%higher than that obtained without airflow.

化危为机——后疫情时期艺术管理教育的发展潜力

本文针对新冠疫情期间艺术教育与管理、文化艺术产业与社会传播所面临的困境,以及相关措施进行调研、分析。本文聚焦艺术管理作为中国院校的新兴专业,其跨学科研究特点,艺科融合的发展趋势,社会文化需求和专业发展问题如何在疫情肆虐全球的背景中建构新型艺术管理共同体理念。同时,根据作者在具体教学管理工作中,针对未来专业人才培养、文化艺术生产和社会发展趋势进行阐述。

新时代文化艺术管理共同体——第十三届中国艺术管理教育学会年会综述

第13届中国艺术管理教育学会年会暨新时代文化艺术管理共同体高峰论坛'于2018年12月1日在中国美术学院盛大开幕。本次大会恰逢中国美术学院建校90周年之际,汇聚全国艺术管理教育开拓者、相关机构负责人、媒体和文创产业领域精英,展开新时期多维度'文化艺术管理共同体'探讨。在大数据、智能化背景下,本次年会倡导共创、共享新时代文化资源的模式,突破地缘、文化、城乡和行业壁垒,以互联互结的智慧,共同激发当下艺术生产、艺术教育向社会文化资源转换、强化艺术教育一体化的实践。年会论坛分别聚焦'智能化时代艺术管理开展的可能性和方式''艺术管理机构与院校交流机制与人才供需''文化政策与产业化运作对艺术管理的影响''不同艺术门类艺术管理教育学科建设的共性与个性探讨'等重要议题。

Analyzing and Optimizing Packet Corruption in RDMA Network

Remote direct memory access (RDMA) has become one of the state-of-the-art high-performance network technologies in datacenters. The reliable transport of RDMA is designed based on a lossless underlying network and cannot endure a high packet loss rate. However, except for switch buffer overflow, there is another kind of packet loss in the RDMA network, i.e., packet corruption, which has not been discussed in depth. The packet corruption incurs long application tail latency by causing timeout retransmissions. The challenges to solving packet corruption in the RDMA network include: 1) packet corruption is inevitable with any remedial mechanisms and 2) RDMA hardware is not programmable. This paper proposes some designs which can guarantee the expected tail latency of applications with the existence of packet corruption. The key idea is controlling the occurring probabilities of timeout events caused by packet corruption through transforming timeout retransmissions into out-of-order retransmissions. We build a probabilistic model to estimate the occurrence probabilities and real effects of the corruption patterns. We implement these two mechanisms with the help of programmable switches and the zero-byte message RDMA feature. We build an ns-3 simulation and implement optimization mechanisms on our testbed. The simulation and testbed experiments show that the optimizations can decrease the flow completion time by several orders of magnitudes with less than 3% bandwidth cost at different packet corruption rates.

Sub-percent precision measurement of neutrino oscillation parameters with JUNO

JUNO is a multi-purpose neutrino observatory under construction in the south of China.This publication presents new sensitivity estimates for the measurement of the △m_(31)^(2),△m_(21)^(2),sin^(2)θ_(12),and sin^(2)θ_(13) oscillation parameters using reactor antineutrinos,which is one of the primary physics goals of the experiment.The sensitivities are obtained using the best knowledge available to date on the location and overburden of the experimental site,the nuclear reactors in the surrounding area and beyond,the detector response uncertainties,and the reactor antineutrino spectral shape constraints expected from the TAO satellite detector.It is found that the △m_(21)^(2) and sin^(2)θ_(12) oscillation parameters will be determined to 0.5%precision or better in six years of data collection.In the same period,the △m_(31)^(2) parameter will be determined to about 0.2%precision for each mass ordering hypothesis.The new precision represents approximately an order of magnitude improvement over existing constraints for these three parameters.

Construction and application of LHAASO data processing platform

Purpose The LHAASO project collects trillions of cosmic ray events every year,generating about 10 PB of raw data annually,which brings big challenges for data processing platform.Method The LHAASO data processing platform is built to handle such a large amount of data,which is composed of some subsystems such as data transfer,data storage,high throughput computing and metadata management.Results and conclusions The platform was under construction since 2018 and has been working well since 2021.In this paper,the details of the design,implementation and performance of the data processing platform are presented.

Feasibility and physics potential of detecting ^(8)B solar neutrinos at JUNO

The Jiangmen Underground Neutrino Observatory(JUNO)features a 20 kt multi-purpose underground liquid scintillator sphere as its main detector.Some of JUNO's features make it an excellent location for^8B solar neutrino measurements,such as its low-energy threshold,high energy resolution compared with water Cherenkov detectors,and much larger target mass compared with previous liquid scintillator detectors.In this paper,we present a comprehensive assessment of JUNO's potential for detecting^8B solar neutrinos via the neutrino-electron elastic scattering process.A reduced 2 MeV threshold for the recoil electron energy is found to be achievable,assuming that the intrinsic radioactive background^(238)U and^(232)Th in the liquid scintillator can be controlled to 10^(-17)g/g.With ten years of data acquisition,approximately 60,000 signal and 30,000 background events are expected.This large sample will enable an examination of the distortion of the recoil electron spectrum that is dominated by the neutrino flavor transformation in the dense solar matter,which will shed new light on the inconsistency between the measured electron spectra and the predictions of the standard three-flavor neutrino oscillation framework.IfDelta m^(2)_(21)=4.8times10^(-5);(7.5times10^(-5))eV^(2),JUNO can provide evidence of neutrino oscillation in the Earth at approximately the 3sigma(2sigma)level by measuring the non-zero signal rate variation with respect to the solar zenith angle.Moreover,JUNO can simultaneously measureDelta m^2_(21)using^8B solar neutrinos to a precision of 20% or better,depending on the central value,and to sub-percent precision using reactor antineutrinos.A comparison of these two measurements from the same detector will help understand the current mild inconsistency between the value of Delta m^2_(21)reported by solar neutrino experiments and the KamLAND experiment.

Diet and Nutrition of Healthcare Workers in COVID-19 Epidemic—Hubei,China,2019

From late January to March,more than 42,000 doctors,nurses,public health workers,and health administrators across China went to Hubei Province to assist in the response to coronavirus disease 2019(COVID-19).There are many studies on nutrition status of affected people amid natural disasters or pandemics(1–3),but the diet and nutrition status of healthcare workers receive little attention.The aim of this article is to provide evidence for addressing this issue by investigating food supply and nutrition status during the COVID-19 response period.