Lenalidomide regulates the CCL21/CCR7/ERK1/2 axis to inhibit migration and proliferation in diffuse large B-cell lymphoma

Background:The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma(DLBCL)has been reported previously.However,the detailed mechanisms of CCR7 in DLBCL,particularly regarding its interaction with lenalidomide treatment,are not fully understood.Methods:Our study utilized bioinformatics approaches to identify hub genes in SU-DHL-2 cell lines treated with lenalidomide compared to control groups.Immunohistochemical data and clinical information from 122 patients with DLBCL were analyzed to assess the correlation of CCR7 and p-ERK1/2 expression with the prognosis of DLBCL.Furthermore,in vitro and in vivo experiments were conducted to clarify the role of CCR7 in the response of DLBCL to lenalidomide treatment.Results:Our bioinformatics analysis pinpointed CCR7 as a hub gene in the context of lenalidomide treatment in DLBCL.Notably,31.14%and 36.0%(44/122)of DLBCL cases showed positive expression for CCR7 and ERK1/2 respectively,establishing them as independent prognostic factors for adverse outcomes in DLBCL via multivariate Cox regression analysis.Additionally,our studies demonstrated that the external application of the protein CCL21 promoted proliferation,migration,invasion,and activation of the ERK1/2 pathway in SU-DHL-2 and OCI-LY3 cell lines with high levels of CCR7 expression.This effect was mitigated by CCR7 silencing through siRNA,application of ERK inhibitors,or lenalidomide treatment.In vivo experiments reinforced the efficacy of lenalidomide,significantly reducing tumor growth rate,tumor mass,serum total LDH levels,and expression of CCR7 and p-ERK1/2 in a SUDHL-2 xenograft model in nude mice(p<0.05).Conclusion:Our study clarifies the potential role of the CCL21/CCR7/ERK1/2 axis in the therapeutic effects of lenalidomide in DLBCL treatment.

阿尔茨海默病居家筛查专家共识

老年人痴呆或认知障碍多由一种以上年龄相关的常见脑部疾病所致。阿尔茨海默病(Alzheimer's disease,AD)是其中最常见的神经变性疾病,且是全球前10位死因中唯一无法治愈或缺乏长期对症疗效的疾病,给个人、家庭和全球经济都带来了巨大的负担。早期及时发现和干预是对抗AD的最佳策略。在过去的30年中,许多研究都提出了降低痴呆风险的方法,2020年《柳叶刀》杂志的痴呆预防报告已阐明通过应对风险因素可以预防或延缓超过40%的痴呆。然而,目前全球医疗体系尚未具备早期或及时发现AD的足够能力。最近的一项研究发现,只有不到10%的轻度认知障碍(mild cognitive impairment,MCI)是在初级医疗机构中诊断出来的。近来,抗淀粉样蛋白β(Amyloid beta,Aβ)抗体药物lecanemab和donanemab被批准上市用于早期AD治疗,以及30年的随访研究证明改善风险因素显著减少AD痴呆的发病率并延长了寿命,使得人们对AD早期识别的关注迅速增加。阿尔茨海默病防治协会(China Association for Alzheimer's Disease,CAAD)认识到居家早期和及时发现AD的重要性,并成立了一个由协会成员、临床医生和研究人员组成的全球AD多领域专家团队,就以下目标达成共识:①为个人、家庭、社区、协会和组织提供专家指导意见;②介绍用于认知障碍和痴呆居家筛查的数字工具和可用资源,并为AD高危人群或疑似患者制定下一步应对策略;③讨论现有可用或将来可能的居家筛查适宜AD生物标志物;④为未来的改进和全球应用建立可行性框架。专家组对于当前可用的证据、工具和资源进行综述,并进一步考量其在AD居家筛查中的价值。

中国阿尔茨海默病早期预防指南(2024)

阿尔茨海默病是一种病因复杂的严重智力致残疾病,目前尚无有效的治疗方法。我国是世界上老年人口最多、增长最快的国家之一,也是阿尔茨海默病发病率较高的国家。因此,如何早期预防阿尔茨海默病的发生,是现今健康领域最重要的课题之一。我们在国内外相关研究的基础上,通过文献循证、干预研究实践、案例分析、经验总结和专家咨询,结合中国老年健康和社会文化特点,体现中国传统医学、武术、养生以及社区组织优势,制订出具有中国特色的阿尔茨海默病早期预防指南,涵盖了个人、家庭和社会三个层面的预防策略,从积极生活态度、社会活动参与、认知训练、体育锻炼、戒烟限酒、营养、睡眠,血压、血糖、血脂管理,体重和其他慢病管理以及中医开展针对阿尔茨海默病的一级预防。本指南仅供个人、家庭和社会开展阿尔茨海默病预防时参考。

A Systematic Review and Meta-analysis for Duhuo Jisheng Decoction Combined with Manipulation in Treatment of Lumbar Disc Herniation

Objective:To systematically evaluate the efficacy and safety of Duhuo Jisheng decoction combined with manipulation in the treatment of lumbar disc herniation.Method:We systematically searched 8 databases at home and abroad.Literature quality of the included studies was evaluated by the bias risk assessment tool of Cochrane collaboration network,and the Meta-analysis was performed by RevMan 5.3 software.Result:A total of 427 related literature were retrieved,and 12 studies were eventually included,involving 1153 patients.All studies were in Chinese.Meta-analysis results showed that the total effective rate of Duhuo Jisheng decoction combined with manipulation in the treatment of LDH was better than that of the control group(RR=1.23,95%CI[1.17,1.29],P<0.00001).Subgroup analysis showed that Duhuo Jisheng decoction combined with manipulation had a more significant effect than conventional treatment(RR=1.34,95%CI[1.20,1.50],P<0.00001),nonsteroidal anti-inflammatory drugs(RR=1.24,95%CI[1.12,1.37],P<0.0001),and Yaotongning capsules(RR=1.19,95%CI[1.10,1.29],P<0.0001).It has obvious advantages in improving VAS scores(MD=-1.19,95%CI-1.19[-1.87,-0.51],P=0.0006),but it has no obvious advantages in improving JOA scores(MD=2.6595%CI[0.06,5.24],P=0.05).In terms of safety,Duhuo Jisheng decoction combined with manipulation treatment reported fewer adverse events.Conclusion:The Duhuo Jisheng decoction combined with manipulation treatment can effectively relieve the clinical symptoms of patients with lumbar disc herniation,with obvious clinical efficacy,and fewer adverse events.But in view of the limitations of clinical studies,there are some limitations in this study,and more studies with high quality of evidence are needed to further confirm its efficacy and safety.

髓源性抑制细胞在多发性骨髓瘤中的研究进展

多发性骨髓瘤(multiple myeloma,MM)是浆细胞恶性增殖性疾病,目前为血液系统第二大肿瘤。虽然蛋白酶体抑制剂和免疫治疗方案的应用改善了MM患者的预后,但大多数仍然无法被治愈,主要是因为MM细胞最终产生耐药。髓源性抑制细胞(myeloid-derived suppressor cells,MDSCs)是骨髓中髓系祖细胞分化受阻而形成的具有显著抑制T细胞免疫应答功能的一群异质性细胞,通过介导免疫抑制性作用促进MM的发展。MDSCs还刺激MM细胞增殖,诱导MM耐药和转移。本文综述了MDSCs在MM发生、发展中表现的多种机制,并探讨针对MDSCs的治疗策略在MM中的可行性及挑战,以期为MM治疗提供参考。

自发性幕上脑出血神经内镜手术与开颅血肿清除术疗效对比分析

目的 对比分析神经内镜手术与开颅血肿清除术治疗自发性幕上脑出血的疗效。方法纳入2019年12月至2020年12月广东省东莞市人民医院诊断与治疗的65例自发性幕上脑出血患者,分别行神经内镜下血肿清除术(内镜组,19例)和开颅血肿清除术(开颅组,46例),记录血肿清除率、再出血率、手术时间、术中出血量、术后重症监护病房(ICU)住院时间、术后气管切开率和术后30 d病死率,术后7 d采用Glasgow昏迷量表(GCS)评估意识状态,术后3个月采用改良Rankin量表(mRS)评估神经功能预后。结果 内镜组患者血肿清除率(t=2.393,P=0.020)和术后7 d GCS评分(t=3.445,P=0.001)高于开颅组,手术时间(t=-13.318,P=0.000)、术中出血量(t=-7.823,P=0.000)、术后ICU住院时间(t=-4.183,P=0.000)、术后气管切开率(χ^(2)=5.277,P=0.022)和术后3个月mRS评分(t=-2.493,P=0.015)低于开颅组。结论 神经内镜手术的血肿清除率更高,术中出血量更少,手术时间和术后ICU住院时间更短,术后气管切开率更低,术后意识状态和神经功能预后更佳,值得临床尝试应用。

How Does Stacking Pressure Affect the Performance of Solid Electrolytes and All-Solid-State Lithium Metal Batteries?

All-solid-state lithium metal batteries(ASSLMBs)with solid electrolytes(SEs)have emerged as a promising alternative to liquid electrolyte-based Li-ion batteries due to their higher energy density and safety.However,since ASSLMBs lack the wetting properties of liquid electrolytes,they require stacking pressure to prevent contact loss between electrodes and SEs.Though previous studies showed that stacking pressure could impact certain performance aspects,a comprehensive investigation into the effects of stacking pressure has not been conducted.To address this gap,we utilized the Li_(6)PS_(5)Cl solid electrolyte as a reference and investigated the effects of stacking pressures on the performance of SEs and ASSLMBs.We also developed models to explain the underlying origin of these effects and predict battery performance,such as ionic conductivity and critical current density.Our results demonstrated that an appropriate stacking pressure is necessary to achieve optimal performance,and each step of applying pressure requires a specific pressure value.These findings can help explain discrepancies in the literature and provide guidance to establish standardized testing conditions and reporting benchmarks for ASSLMBs.Overall,this study contributes to the understanding of the impact of stacking pressure on the performance of ASSLMBs and highlights the importance of careful pressure optimization for optimal battery performance.

Impacts of Future Changes in Heavy Precipitation and Extreme Drought on the Economy over South China and Indochina

Heavy precipitation and extreme drought have caused severe economic losses over South China and Indochina(INCSC)in recent decades.Given the areas with large gross domestic product(GDP)in the INCSC region are distributed along the coastline and greatly affected by global warming,understanding the possible economic impacts induced by future changes in the maximum consecutive 5-day precipitation(RX5day)and the maximum consecutive dry days(CDD)is critical for adaptation planning in this region.Based on the latest data released by phase 6 of the Coupled Model Intercomparison Project(CMIP6),future projections of precipitation extremes with bias correction and their impacts on GDP over the INCSC region under the fossil-fueled development Shared Socioeconomic Pathway(SSP5-8.5)are investigated.Results indicate that RX5day will intensify robustly throughout the INCSC region,while CDD will lengthen in most regions under global warming.The changes in climate consistently dominate the effect on GDP over the INCSC region,rather than the change of GDP.If only considering the effect of climate change on GDP,the changes in precipitation extremes bring a larger impact on the economy in the future to the provinces of Hunan,Jiangxi,Fujian,Guangdong,and Hainan in South China,as well as the Malay Peninsula and southern Cambodia in Indochina.Thus,timely regional adaptation strategies are urgent for these regions.Moreover,from the sub-regional average viewpoint,over two thirds of CMIP6 models agree that maintaining a lower global warming level will reduce the economic impacts from heavy precipitation over the INCSC region.

Stability-Considered Lane Keeping Control of Commercial Vehicles Based on Improved APF Algorithm

Regarding the lane keeping system,path tracking accuracy and lateral stability at high speeds need to be taken into account especially for commercial vehicles due to the characteristics of larger mass,longer wheelbase and higher mass center.To improve the performance mentioned above comprehensively,the control strategy based on improved artificial potential field(APF)algorithm is proposed.In the paper,time to lane crossing(TLC)is introduced into the potential field function to enhance the accuracy of path tracking,meanwhile the vehicle dynamics parameters including yaw rate and lateral acceleration are chosen as the repulsive force field source.The lane keeping controller based on improved APF algorithm is designed and the stability of the control system is proved based on Lyapunov theory.In addition,adaptive inertial weight particle swarm optimization algorithm(AIWPSO)is applied to optimize the gain of each potential field function.The co-simulation results indicate that the comprehensive evaluation index respecting lane tracking accuracy and lateral stability is reduced remarkably.Finally,the proposed control strategy is verified by the HiL test.It provides a beneficial reference for dynamics control of commercial vehicles and enriches the theoretical development and practical application of artificial potential field method in the field of intelligent driving.

Engineering electrolyte additives for stable zinc-based aqueous batteries:Insights and prospects

Zn-based aqueous batteries(ZABs) are gaining widespread popularity due to their low cost and high safety profile. However, the application of ZABs faces significant challenges, such as dendrite growth and parasitic reactions of metallic Zn anodes. Therefore, achieving high-energy–density ZABs necessitates addressing the fundamental thermodynamics and kinetics of Zn anodes. Various strategies are available to mitigate these challenges, with electrolyte additive engineering emerging as one of the most efficient and promising approaches. Despite considerable research in this field, a comprehensive understanding of the intrinsic mechanisms behind the high performance of electrolyte additives remains limited. This review aims to provide a detailed introduction to functional electrolyte additives and thoroughly explore their underlying mechanisms. Additionally, it discusses potential directions and perspectives in additive engineering for ZABs, offering insights into future development and guidelines for achieving high-performance ZABs.

Passive neutron multiplicity device for^(240)Pu measurement based on FPGA

A passive neutron multiplicity measurement device,FH-NCM/S1,based on field-programmable gate arrays(FPGAs),is developed specifically for measuring the mass of plutonium-240(^(240)Pu)in mixed oxide fuel.FH-NCM/S1 adopts an inte-grated approach,combining the shift register analysis mode with the pulse-position timestamp mode using an FPGA.The optimal effective length of the^(3)He neutron detector was determined to be 30 cm,and the thickness of the graphite reflector was ascertained to be 15 cm through MCNP simulations.After fabricating the device,calibration measurements were per-formed using a^(252)Cf neutron source;a detection efficiency of 43.07%and detector die-away time of 55.79μs were observed.Nine samples of plutonium oxide were measured under identical conditions using the FH-NCM/S1 in shift register analysis mode and a plutonium waste multiplicity counter.The obtained double rates underwent corrections for detection efficiency(ε)and double gate fraction(f_(d)),resulting in corrected double rates(D_(c)),which were used to validate the accuracy of the shift register analysis mode.Furthermore,the device exhibited fluctuations in the measurement results,and within a single 20 s measurement,these fluctuations remained below 10%.After 30 cycles,the relative error in the mass of^(240)Pu was less than 5%.Finally,correlation calculations confirmed the robust consistency of both measurement modes.This study holds specific significance for the subsequent design and development of neutron multiplicity devices.

Mechanism of high temperature oxidation of Inconel 625 superalloy with various solution and ageing heat treatment processes

The high-temperature oxidation behaviour of the Inconel 625 alloy at 950℃ was investigated after different ageing treatments.The effect of heat treatment on the oxidation behaviour of the alloy was analysed by characterizing the structure and elemental distribution before and after oxidation.The results reveal that the two ageing treatments at 650℃ for 500 h and at 750℃ for 400 h both reduced the oxidation mass gain.After oxidation at 950℃,an outer Cr_(2)O_(3) layer and inner Al_(2)O_(3) are identified as the main oxidation products.Moreover,Nb_(2)O_(5) andδ(Ni_(3)Nb)phases precipitated after oxidation.The ageing treatments cause the rapid generation of a dense Cr_(2)O_(3) layer on the surface,which prevents the diffusion of oxygen into the matrix,reduce the Al_(2)O_(3) inward growth depth,and improve the oxidation resistance of the alloy.

Probabilistic modeling of multifunction radars with autoregressive kernel mixture network

The task of modeling and analyzing intercepted multifunction radars(MFRs)pulse trains is vital for cognitive electronic reconnaissance.Existing methodologies predominantly rely on prior information or heavily constrained models,posing challenges for non-cooperative applications.This paper introduces a novel approach to model MFRs using a Bayesian network,where the conditional probability density function is approximated by an autoregressive kernel mixture network(ARKMN).Utilizing the estimated probability density function,a dynamic programming algorithm is proposed for denoising and detecting change points in the intercepted MFRs pulse trains.Simulation results affirm the proposed method's efficacy in modeling MFRs,outperforming the state-of-the-art in pulse train denoising and change point detection.

Wideband spectrum sensing using step-sampling based on the multipath nyquist folding receiver

Wideband spectrum sensing with a high-speed analog-digital converter(ADC) presents a challenge for practical systems.The Nyquist folding receiver(NYFR) is a promising scheme for achieving cost-effective real-time spectrum sensing,which is subject to the complexity of processing the modulated outputs.In this case,a multipath NYFR architecture with a step-sampling rate for the different paths is proposed.The different numbers of digital channels for each path are designed based on the Chinese remainder theorem(CRT).Then,the detectable frequency range is divided into multiple frequency grids,and the Nyquist zone(NZ) of the input can be obtained by sensing these grids.Thus,high-precision parameter estimation is performed by utilizing the NYFR characteristics.Compared with the existing methods,the scheme proposed in this paper overcomes the challenge of NZ estimation,information damage,many computations,low accuracy,and high false alarm probability.Comparative simulation experiments verify the effectiveness of the proposed architecture in this paper.

Surface encapsulation of layered oxide cathode material with NiTiO_(3) for enhanced cycling stability of Na-ion batteries

In Na-ion batteries,O3-type layered oxide cathode materials encounter challenges such as particle cracking,oxygen loss,electrolyte side reactions,and multi-phase transitions during the charge/discharge process.This study focuses on surface coating with NiTiO_(3) achieved via secondary heat treatment using a coating precursor and the surface material.Through in-situ x-ray diffraction(XRD)and differential electrochemical mass spectrometry(DEMS),along with crystal structure characterizations of post-cycling materials,it was determined that the NiTiO_(3) coating layer facilitates the formation of a stable lattice structure,effectively inhibiting lattice oxygen loss and reducing side reaction with the electrolyte.This enhancement in cycling stability was evidenced by a capacity retention of approximately 74%over 300 cycles at 1 C,marking a significant 30%improvement over the initial sample.Furthermore,notable advancements in rate performance were observed.Experimental results indicate that a stable and robust surface structure substantially enhances the overall stability of the bulk phase,presenting a novel approach for designing layered oxide cathodes with higher energy density.

Indirect neutron radiography experiment on dummy nuclear fuel rods for pressurized water reactors at CMRR

Nuclear energy is a vital source of clean energy that will continue to play an essential role in global energy production for future generations.Nuclear fuel rods are core components of nuclear power plants,and their safe utilization is paramount.Due to its inherent high radioactivity,indirect neutron radiography(INR)is currently the only viable technology for irradiated nuclear fuel rods in the field of energy production.This study explores the experimental technique of indirect neutron computed tomography(INCT)for radioactive samples.This project includes the development of indium and dysprosium conversion screens of different thicknesses and conducts resolution tests to assess their performance.Moreover,pressurized water reactor(PWR)dummy nuclear fuel rods have been fabricated by self-developing substitute materials for cores and outsourcing of mechanical processing.Experimental research on the INR is performed using the developed dummy nuclear fuel rods.The sparse reconstruction technique is used to reconstruct the INR results of 120 pairs of dummy nuclear fuel rods at different angles,achieving a resolution of 0.8 mm for defect detection using INCT.

Current status of surgical treatment of colorectal liver metastases

Liver metastasis （LM） is one of the major causes of death in patients with colorectal cancer （CRC）. Approxi-mately 60% of CRC patients develop LM during the course of their illness. About 85% of these patients have unresectable disease at the time of presenta-tion. Surgical resection is currently the only curative treatment for patients with colorectal LM （CRLM）. In recent years, with the help of modern multimodality therapy including systemic chemotherapy, radiation therapy, and surgery, the outcomes of CRLM treatment have signifcantly improved. This article summarizes the current status of surgical treatment of CRLM including evaluation of resectability, treatment for resectable LM, conversion therapy and liver transplantation for unresectable cases, liver resection for recurrent CRLM and elderly patients, and surgery for concomitanthepatic and extra-hepatic metastatic disease （EHMD）. We believe that with the help of modern multimodality therapy, an aggressive oncosurgical approach should be implemented as it has the possibility of achieving a cure, even when EHMD is present in patients with CRLM.

内镜下经鼻入路切除颅咽管瘤(附65例报告)

目的探讨内镜下经鼻入路切除颅咽管瘤的临床经验和应用价值。方法回顾性分析2012年2月-2016年5月使用内镜下经鼻入路切除的65例颅咽管瘤患者的临床资料,综合评价治疗效果、并发症发生率及随访结果。结果肿瘤全切52例(80.0%),次全切11例(16.9%),部分切除2例(3.1%);术中发现垂体柄共57例,保留41例(71.9%);术后视力改善31例(47.7%),6例维持在术前水平,1例术后视力下降;术后出现垂体功能下降21例(32.3%);术后短暂性尿崩45例(69.2%),长期尿崩9例(13.8%);4例(6.2%)患者出现脑脊液漏,均伴随颅内感染,均予以再次修补,成功3例,死亡1例;围手术期死亡3例(4.6%)。52例患者接受随访,时间4.0~45.0个月,平均20.8个月,44例(84.6%)恢复正常生活,8例(15.4%)出现肥胖,2例复发,尚无死亡病例。结论内镜下经鼻入路切除颅咽管瘤安全、有效、微创,具有其独到的优势。

2023中国阿尔茨海默病数据与防控策略

本报告汇总了阿尔茨海默病及痴呆相关领域现有的最新数据,分析了我国阿尔茨海默病的流行病学、疾病负担、诊断治疗、风险因素、康复护理和疾病筛查等各方面的现状、问题以及趋势,针对目前中国民众和政策制定者最关心的问题,例如:阿尔茨海默病基本数据是怎样的?为什么知晓率相对提高,但是患者就诊愿望相对不高?如何采用有效的措施来应对,等等,提出了目前阿尔茨海默病的防控策略。特别强调了要大力开发经过验证的早期筛查和诊断工具,提供更有效治疗的创新药物,以及鼓励和建立全国性属地化社会互助支持网络。本报告期望能对医学专业人士、患者、家属和照护者、政府政策制定人员、养老机构等有所帮助,能为阿尔茨海默病的防治工作提供支撑,为相关卫生政策的制定提供依据和建议,有助于提高公众对阿尔茨海默病的认识,以期缓解我国阿尔茨海默病疾病的整体负担,推动我国健康老龄化的实现。

2022年中国阿尔茨海默病知晓与需求现状调查

目的:为了更加全面了解我国老年性痴呆(阿尔茨海默病)防治工作的现状及发展趋势,更加精准地为防治工作提供政策咨询及对策建议,开展了本次阿尔茨海默病知晓与需求现状调查。对象与方法:通过线上问卷,对18岁以上普通成年居民进行调查,居民来自全国各个省市自治区和港澳台地区,调查总样本为20671人。结果:被调查人群阿尔茨海默病的总知晓率为95.9%,经统计学标化后为91.5%。不同人群对阿尔茨海默病的总知晓率存在一定差异;认为阿尔茨海默病或老年痴呆病可以预防的比例是87.9%;被调查居民觉得居家照护患者遇到的困难最主要表现在精力不够、照护能力不足和缺少专业的失智养老服务机构;患者的最主要的照护者是配偶,占47.9%,对阿尔茨海默病康复治疗内容了解的仅占23.3%;对合理安排患者营养知晓率为39%,在被调查人群中,主动愿意去医院就诊的比例只有12.9%,其中农村居民和低学历居民主动就诊愿望较低。结论:本次调查结果为更加精准地制定阿尔茨海默病防治对策,提供了重要的科学依据。