CHIP相关基因与MPN患者心脑血管事件的风险分析

目的:分析骨髓增殖性肿瘤(MPN)患者不确定潜能的克隆性造血(CHIP)相关基因突变谱和临床特征,探讨CHIP相关基因与其心脑血管事件(CCE)的相关性及可能作用机制。方法:回顾性分析2019年8月-2022年7月首都医科大学附属北京安贞医院血液科收治的73例MPN患者的临床资料和二代测序结果,采用Logistic回归分析CHIP相关基因、炎症细胞因子对MPN患者CCE的影响。结果:55例(75.3%)MPN患者检出CHIP相关基因,原发性血小板增多症(ET)和真性红细胞增多症(PV)患者CHIP相关基因各突变频率差异无统计学意义。CHIP相关基因突变以单基因形式为主,检出率从高至低依次为JAK2V617F(63.0%,46/73)、ASXL1(16.4%,12/73)、TET2(11.0%,8/73)、DNMT3A(9.6%,7/73)、SRSF2(6.9%,5/73)、SF3B1(4.1%,3/73)、TP53(1.4%,1/73)和PPMID(1.4%,1/73)。年龄>60岁患者CHIP相关基因检出率明显高于≤60岁者[91.7%(33/36)vs 59.5%(22/37)]。27例(37.0%)MPN患者伴CCE(MPN/CCE),2次CCE者5例,均为动脉事件。CCE组患者年龄(62.8±12.8 vs 53.9±15.8岁,P=0.015)、IL-1β水平(17.7±26.0vs 4.3±8.6,P=0.012)、IL-8水平(360.7±598.6 vs 108.3±317.0,P=0.045)、血栓形成史(29.6%vs 2.2%,P=0.020)和CHIP相关基因检出率(88.9%vs 67.4%,P=0.040)高于无CCE组。多因素Logistic回归分析结果显示,年龄(OR=0.917,95%CI:0.843-0.999,P=0.047)、血栓形成史(OR=34.148,95%CI:2.392-487.535,P=0.009)、任何1个CHIP相关基因突变(OR=16.065,95%CI:1.217-212.024,P=0.035)和IL-1β水平升高(OR=0.929,95%CI:0.870-0.992,P=0.027)均是MPN/CCE的独立危险因素;CHIP相关单基因突变与MPN/CCE无关,但DNMT3A(OR=88.717,95%CI:2.690-292.482,P=0.012)、ASXL1(OR=7.941,95%CI:1.045-60.353,P=0.045)突变是PV/CCE的独立危险因素。结论:MPN患者CHIP相关基因突变率高,尤其是60岁以上患者;高龄、血栓形成史、CHIP相关基因突变和IL-1β水平升高是MPN发生CCE的独立危险因素。DNMT3A、ASXL1单基因突变是PV患者CCE的独立危险因素。CHIP相关基因突变及炎症细胞因子IL-1β升高是MPN新的CCE危险因素。

替普瑞酮通过E3泛素连接酶CHIP减轻LPS引起的心肌炎症反应和心功能障碍

目的:探究替普瑞酮又称香叶基香叶基丙酮,GGA)对脂多糖(LPS)诱导的心功能障碍的治疗作用及机制。方法:(1)取8周龄C57BL/6雄性野生型小鼠和热休克蛋白70(HSP70)羧基末端相互作用蛋白(CHIP)基因敲除小鼠,随机分为对照组、LPS组、LPS+GGA组和GGA组,每组8只。用腹腔注射LPS(25 mg/kg)的方法建立模型,于LPS刺激后1 h给予小鼠腹腔注射GGA(100 mg/kg)。利用小动物超声系统评估小鼠心脏功能;采集各组小鼠血清,检测血清肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)水平;HE染色观察病理学改变;ELISA检测心脏组织中炎症因子肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)的水平;Western blot检测各组心脏组织HSP70、CHIP、核转运蛋白α2(KPNA2)、髓过氧化物酶(MPO)、血管细胞黏附分子(VCAM)和细胞间黏附分子(ICAM)的蛋白表达以及细胞核NF-κB的水平。(2)利用小鼠心肌细胞HL-1,建立LPS刺激的离体细胞炎症模型。ELISA检测细胞上清中TNF-α和IL-6的水平;Western blot检测心肌细胞中HSP70、CHIP和KPNA2蛋白表达;免疫荧光染色观察细胞核NF-κB的表达。结果:(1)GGA有效改善LPS刺激小鼠的心脏功能,显著提高射血分数和左室短轴缩短率(P<0.01),减少血清CK-MB和LDH含量(P<0.01),减轻心肌损伤。(2)GGA显著减少LPS引起的TNF-α和IL-6炎症因子的释放(P<0.01),以及NF-κB的入核,降低心肌组织中KPNA2、MPO、VCAM和ICAM蛋白表达,增加心肌组织和细胞HSP70的水平(P<0.01)。(3)在CHIP基因敲除的心肌细胞和小鼠中,GGA不能抑制LPS引起的炎症反应,失去了改善LPS刺激小鼠心脏功能的作用。结论:GGA能够减轻LPS引起的心功能障碍,其作用机制与升高HSP70的表达,促进CHIP的活化,减少NF-κB的入核,抑制炎症因子的释放有关。CHIP的敲除使GGA丧失了减轻LPS诱导的炎症反应和心肌损伤的作用。

Efficient stochastic parallel gradient descent training for on-chip optical processor

In recent years,space-division multiplexing(SDM)technology,which involves transmitting data information on multiple parallel channels for efficient capacity scaling,has been widely used in fiber and free-space optical communication sys-tems.To enable flexible data management and cope with the mixing between different channels,the integrated reconfig-urable optical processor is used for optical switching and mitigating the channel crosstalk.However,efficient online train-ing becomes intricate and challenging,particularly when dealing with a significant number of channels.Here we use the stochastic parallel gradient descent(SPGD)algorithm to configure the integrated optical processor,which has less com-putation than the traditional gradient descent(GD)algorithm.We design and fabricate a 6×6 on-chip optical processor on silicon platform to implement optical switching and descrambling assisted by the online training with the SPDG algorithm.Moreover,we apply the on-chip processor configured by the SPGD algorithm to optical communications for optical switching and efficiently mitigating the channel crosstalk in SDM systems.In comparison with the traditional GD al-gorithm,it is found that the SPGD algorithm features better performance especially when the scale of matrix is large,which means it has the potential to optimize large-scale optical matrix computation acceleration chips.

Simulation and fabrication of in vitro microfluidic microelectrode array chip for patterned culture and electrophysiological detection of neurons

To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.

On-chip quantum NOON state sensing for temperature and humidity

A maximal photon number entangled state,namely NOON state,can be adopted for sensing with a quantum enhancedprecision.In this work,we designed silicon quantum photonic chips containing two types of Mach-Zehnder interferometerswherein the two-photon NOON state,sensing element for temperature or humidity,is generated.Compared with classicallight or single photon case,two-photon NOON state sensing shows a solid enhancement in the sensing resolution andprecision.As the first demonstration of on-chip quantum photonic sensing,it reveals the advantages of photonic chips forhigh integration density,small-size,stability for multiple-parameter sensing serviceability.A higher sensing precision isexpected to beat the standard quantum limit with a higher photon number NOON state.

A Fully-Integrated Memristor Chip for Edge Learning

It is still challenging to fully integrate computing in memory chip as edge learning devices.In recent work published on Science,a fully-integrated chip based on neuromorphic memristors was developed for edge learning as artificial neural networks with functionality of synapses,dendrites,and somas.A crossbar-array memristor chip facilitated edge learning including hardware realization,learning algorithm,and cycle-parallel sign-and threshold-based learning(STELLAR)scheme.The motion control and demonstration platforms were executed to improve the edge learning ability for adapting to new scenarios.

Curriculum Ideological and Political Teaching and Practice of Study Tour Course Design in Higher Vocational Colleges: A Case Study of Qingdao Preschool Education College

Curriculum ideology and politics are critical for colleges and universities to fulfill theirfundamental mission of fostering moral and intellectual development. Within this framework, professionalcourses serve as the primary vehicles for integrating ideological and political education. Specifically, inthe field of study tours, the Study Tour Course Design emerges as a pivotal component for actualizingthe educational objectives of such programs. To construct a robust ideological and political curriculum,it is essential to devise a comprehensive system that aligns with professional teaching standards, industrybenchmarks, and vocational skill requirements. This involves a thorough exploration of ideologicaland political elements within the curriculum, ensuring their seamless integration throughout the coursedevelopment process.

Simplified quantitative analysis method and its application in the insitu synthesized copper-based azide chips

Copper-based azide(Cu(N_(3))2 or CuN_(3),CA)chips synthesized by in-situ azide reaction and utilized in miniaturized explosive systems has become a hot research topic in recent years.However,the advantages of in-situ synthesis method,including small size and low dosage,bring about difficulties in quantitative analysis and differences in ignition capabilities of CA chips.The aim of present work is to develop a simplified quantitative analysis method for accurate and safe analysis of components in CA chips to evaluate and investigate the corresponding ignition ability.In this work,Cu(N_(3))2 and CuN_(3)components in CA chips were separated through dissolution and distillation by utilizing the difference in solubility and corresponding content was obtained by measuring N_(3)-concentration through spectrophotometry.The spectrophotometry method was optimized by studying influencing factors and the recovery rate of different separation methods was studied,ensuring the accuracy and reproducibility of test results.The optimized method is linear in range from 1.0-25.0 mg/L,with a correlation coefficient R^(2)=0.9998,which meets the requirements of CA chips with a milligram-level content test.Compared with the existing ICP method,component analysis results of CA chips obtained by spectrophotometry are closer to real component content in samples and have satisfactory accuracy.Moreover,as its application in miniaturized explosive systems,the ignition ability of CA chips with different component contents for direct ink writing CL-20 and the corresponding mechanism was studied.This study provided a basis and idea for the design and performance evaluation of CA chips in miniaturized explosive systems.

A novel integrated microfluidic chip for on-demand electrostatic droplet charging and sorting

On-demand droplet sorting is extensively applied for the efficient manipulation and genome-wide analysis of individual cells.However,state-of-the-art microfluidic chips for droplet sorting still suffer from low sorting speeds,sample loss,and labor-intensive preparation procedures.Here,we demonstrate the development of a novel microfluidic chip that integrates droplet generation,on-demand electrostatic droplet charging,and high-throughput sorting.The charging electrode is a copper wire buried above the nozzle of the microchannel,and the deflecting electrode is the phosphate buffered saline in the microchannel,which greatly simplifies the structure and fabrication process of the chip.Moreover,this chip is capable of high-frequency droplet generation and sorting,with a frequency of 11.757 kHz in the drop state.The chip completes the selective charging process via electrostatic induction during droplet generation.On-demand charged microdroplets can arbitrarilymove to specific exit channels in a three-dimensional(3D)-deflected electric field,which can be controlled according to user requirements,and the flux of droplet deflection is thereby significantly enhanced.Furthermore,a lossless modification strategy is presented to improve the accuracy of droplet deflection or harvest rate from 97.49% to 99.38% by monitoring the frequency of droplet generation in real time and feeding it back to the charging signal.This chip has great potential for quantitative processing and analysis of single cells for elucidating cell-to-cell variations.

Single event effects evaluation on convolution neural network in Xilinx 28 nm system on chip

Convolutional neural networks(CNNs) exhibit excellent performance in the areas of image recognition and object detection, which can enhance the intelligence level of spacecraft. However, in aerospace, energetic particles, such as heavy ions, protons, and alpha particles, can induce single event effects(SEEs) that lead CNNs to malfunction and can significantly impact the reliability of a CNN system. In this paper, the MNIST CNN system was constructed based on a 28 nm systemon-chip(SoC), and then an alpha particle irradiation experiment and fault injection were applied to evaluate the SEE of the CNN system. Various types of soft errors in the CNN system have been detected, and the SEE cross sections have been calculated. Furthermore, the mechanisms behind some soft errors have been explained. This research will provide technical support for the design of radiation-resistant artificial intelligence chips.

Rapid fabrication of modular 3D paper-basedmicrofluidic chips using projection-based 3D printing

Paper-based microchips have different advantages,such as better biocompatibility,simple production,and easy handling,making them promising candidates for clinical diagnosis and other fields.This study describes amethod developed to fabricate modular three-dimensional(3D)paper-based microfluidic chips based on projection-based 3D printing(PBP)technology.A series of two-dimensional(2D)paper-based microfluidic modules was designed and fabricated.After evaluating the effect of exposure time on the accuracy of the flow channel,the resolution of this channel was experimentally analyzed.Furthermore,several 3D paper-based microfluidic chips were assembled based on the 2D ones using different methods,with good channel connectivity.Scaffold-based 2D and hydrogel-based 3D cell culture systems based on 3D paper-based microfluidic chips were verified to be feasible.Furthermore,by combining extrusion 3D bioprinting technology and the proposed 3D paper-based microfluidic chips,multiorgan microfluidic chips were established by directly printing 3D hydrogel structures on 3D paperbased microfluidic chips,confirming that the prepared modular 3D paper-based microfluidic chip is potentially applicable in various biomedical applications.

Exploring Marine Literature in University Curriculum Development from the Perspective of a Maritime Power

As a nation with an extensive coastline,China has regions that have flourished and prospered due to the sea,and marine culture has developed vigorously,with marine literature being an indispensable component.In the new era,the youth in higher education institutions should focus on the ocean,listen to,inherit,and promote marine literature,aligning with policies to establish confidence in marine culture.Research indicates that the integration of marine literature offers numerous benefits to students’learning and future development,playing a crucial role in education.This paper will analyze the significance of marine literature in education,its current development status,and explore the application value of Chinese marine literature in educational settings.

On the Reform of ESP Curriculum for New Medicine Discipline

This paper discusses the reform of ESP(English for special purpose)curriculum in Chinese medicine universities for new medicine discipline.The reconstruction of ESP curriculum and evaluation system can better meet different students’needs,broaden their horizons,and cultivate compound talents of Chinese medicine with more competitiveness and international vision.

Curriculum Development and Teachers for Cultivating OECD Student Agency in Japan:From an Examination of Educational Thought,Educational System,History,and Contemporary Science and Mathematics Education Practices

The purpose of this paper is to examine the development of a curriculum in Japan to foster the agency(OECD Student Agency)necessary for children living in the future,as outlined in the OECD Education2030 Project,and the role of teachers who implement this curriculum.Therefore,I aim to achieve this goal by taking an overview of educational thought,educational systems and history,and examining several initiatives in the OECD Project and the situation of a Japanese high school that practices science and mathematics education.As a result of analyzing previous research and the narratives obtained from interviews with Teacher A(pseudonym)of a certain F High School(pseudonym),it was found that school education should not simply teach subjects,but should aim to enable student to help student exercise agency in the future.It was suggested that it is not necessary to add content to the curriculum,but rather to prepare to provide students with competencies that will enable them to use the content in various contexts,situations,and circumstances,suggesting that in order to discover such important competencies,teachers and other related parties are required to implement curricula that allow students to slowly and carefully explore the competencies surrounding the content,and to conceive and build curricula that include both hidden and intended curriculum that allows student to reflect on the curriculum they have achieved.

Formulation of Work-Study Combined and Result-Oriented Integrated Curriculum Standards

According to the Annex Technical Regulations for Integrated Curriculum Development(Trial)in Document No.30 of the General Office of the Ministry of Human Resources and Social Security(2012),this paper studies the formulation of the curriculum standards for the integration of Chinese medicinal materials production.We focus on the formulation ideas of the curriculum standards for the integration of Chinese medicinal materials production,the formulation process of the curriculum standards for the integration of Chinese medicinal materials production,including the description of typical work tasks,the determination of curriculum objectives,the analysis of study content,the description of referential study tasks,teaching implementation suggestions,assessment and evaluation suggestions,which can provide a reference for the development and research of other related integrated courses.

Designing a medical ethics curriculum in ophthalmology

Ethical principles form a bedrock to medical practice in any specialty,guiding physicians to appropriate attitudes and behaviors.A formal ethics curriculum can be difficult to generate de novo in an ophthalmology training program.A number of barriers exist in most ophthalmology departments:trainees may think ethics is of secondary importance compared to core basic and clinical science topics;most ophthalmology faculty have no formal degree in medical ethics;there is limited didactic time with competing academic,clinical,and surgical priorities;work-hours regulations may limit the time available to deliver“para-professional”lectures;and there is a belief that the medical ethics lectures during medical school is a sufficient amount of coursework to last through a physician’s career with no need for continuing professional development.The four pillars of medical ethics are beneficence,non-maleficence,autonomy,and justice.In addition,morals,ethics,and professionalism are important aspects of sound medical practice.A curriculum specific to medical ethics in ophthalmology can be developed in any of our sub-specialties and include lectures,curated readings,case rounds,and clinic wrap-up sessions.Ethical considerations are part of everyday clinical practice,and a structured ethics curriculum can be incorporated into ophthalmology training programs.The concept of backward design can be used to structure the curriculum,starting with the expected outcome,then designing authentic assessments,and finally putting together a learning plan that has students actively involved in ethical discussions.This paper will provide a guide to developing an ethics curriculum for an ophthalmology training program utilizing the concept of backwards design and guide the reader through the process of developing expected learning outcomes,authentic assessments,and a unified learning plan.

Significance of“Printing English”in the Curriculum Setting of Business English Majors(Publishing Direction)

With the development of the global economy and the quick growth of international exchanges,Business English major plays an increasingly important role in higher education.The training goal of Business English major(publishing direction)has gradually shifted from the improvement of studentslanguage abilities to the cultivation of more specialized business knowledge and publishing skills.As an important course for Business English majors(publishing direction),Printing English is of great significance for cultivating studentsprofessional quality,professional competitiveness,career development,and practical ability.From the perspective of curriculum setting,it is necessary to re-understand the importance of Printing English in the curriculum setting of Business English major(publishing direction),and put forward corresponding teaching methods and strategies.

Applying Design Thinking in Ecotourism Curriculum Design: The Educational Design Ladder

The design thinking approach transforms student’s learning process to connect with real-world experience, making connections between knowledge and improving critical thinking and problem-solving capability. Previous research has focused on what design thinking is taught (content) and how it is taught (learning modes and assessment). However, there needs to be an integrative approach in the context of ecotourism education. Therefore, applying Wrigley and Straker’s Educational Design Ladder mode, this study develops an Ecotourism Design Thinking Curriculum framework to combine the ecotourism content, teaching/learning mode and assessment.

College English Curriculum Reform in the Context of New Engineering Education:Taking Wuhan University of Technology as an Example

With the introduction of“new engineering,new medical science,new agricultural science,and new liberal arts”construction,the reform of college English teaching is also imperative.Scholars nationwide have conducted attempts in different aspects of college English teaching and produced fruitful results.Yet,more efforts should be made.This paper discusses the reforms made by Wuhan University of Technology,focusing on the reformation of curriculum.

Exploration on the Integration of Curriculum Ideological and Political Concept into the Teaching Design of"Culinary Raw Materials":A Case Study of Livestock and Poultry Raw Materials

Comprehensively promoting curriculum ideological and political education is a strategic measure to implement the fundamental task of establishing moral integrity and educating people.Culinary raw materials is the core curriculum of culinary majors,which is rich in ideological and political elements.In this study,taking livestock and poultry raw materials as an example,the teaching design of integrating curriculum ideological and political education into culinary raw materials were investigated by sorting out its teaching contents and excavating its ideological and political elements.Taking livestock and poultry raw materials in Teochew Cuisine Raw Materials as an example,the teaching design of curriculum ideological and political education was conducted,aiming to provide some reference and guidance for curriculum ideological and political education of the curriculum.