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The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1951-1964页

作者： Longsheng Wang Jie Zhang wenxin Zhang Mingming Zheng Hongjie Guo xiaohui Pan wen Li Bo Yang Ling Ding Zhejiang Province Key Laboratory of Anti-Cancer Drug Research Institute of Pharmacology and ToxicologyCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China The Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 310018China Nanhu Brain-Computer Interface Institute Hangzhou 311100China

Adenosine(Ado)is significantly elevated in the tumor microenvironment(TME)compared to normal tissues.It binds to adenosine receptors(AdoRs),suppressing tumor antigen presentation and immune cell activation,thereby inhibiting tumor adaptive immunity.Ado downregulates major histocompatibility complex II(MHC II)and co-stimulatory factors on dendritic cells(DCs)and macrophages,inhibiting antigen presentation.It suppresses anti-tumor cytokine secretion and T cell activation by disrupting T cell receptor(TCR)binding and signal transduction.Ado also inhibits chemokine secretion and KCa3.1 channel activity,impeding effector T cell trafficking and infiltration into the tumor site.Furthermore,Ado diminishes T cell cytotoxicity against tumor cells by promoting immune-suppressive cytokine secretion,upregulating immune checkpoint proteins,and enhancing immune-suppressive cell activity.Reducing Ado production in the TME can significantly enhance anti-tumor immune responses and improve the efficacy of other immunotherapies.Preclinical and clinical development of inhibitors targeting Ado generation or AdoRs is underway.Therefore,this article will summarize and analyze the inhibitory effects and molecular mechanisms of Ado on tumor adaptive immunity,as well as provide an overview of the latest advancements in targeting Ado pathways in anti-tumor immune responses.

关键词： Adenosine Adenosine receptors Adenosine-generating enzymes Tumor microenvironment Immune suppression Immune escape Clinical treatment Targeting drugs

Efficacy and safety of clarithromycin for patients with sepsis or septic shock:a systematic review and meta-analysis

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Emergency and Critical Care Medicine 2024年第2期4卷 90-96页

作者： Pengyue Zhao Renqi Yao Jiaqi Yang Wei wen Yongming Yao xiaohui Du Department of General Surgery First Medical Center of the Chinese PLA General HospitalBeijingChina Translational Medicine Research Center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General HospitalBeijingChina Department of Burn Surgery the First Affiliated Hospital of Naval Medical UniversityShanghaiChina Department of General Surgery Hainan Hospital of Chinese PLA General HospitalSanyaHainanChina.

Background:Clarithromycin exerts an immunomodulatory role in several human diseases.However,whether this effect improves the prognosis in patients with sepsis remains controversial,and higher levels of clinical evidence are urgently needed.To the best of our knowledge,no meta-analysis to date has reported the clinical efficacy and safety of clarithromycin in sepsis.Methods:A comprehensive literature search of PubMed,EMBASE,and the Cochrane Library was conducted up to December 31,2022.Only randomized controlled trials comparing the clinical efficacy and safety of clarithromycin with controls among patients with sepsis or septic shock were included.Data were pooled by applying a fixed-effects model and a relative risk(RR)estimate with 95%confidence intervals(CIs)using Review Manager(version 5.3;Cochrane Collaboration,Copenhagen,Denmark).Results:Three randomized controlled trials involving a total of 910 patients were included.The pooled results confirmed that clarithromycin had no beneficial effect on progression to multiple organ dysfunction syndrome(RR:1.51;95%CI:1.02-2.25;P=0.04;I^(2)=0%),28-day mortality(RR:1.09;95%CI:0.87-1.36;P=0.46;I^(2)=0%),and 90-day mortality(RR:0.86;95%CI:0.71-1.03;P=0.10;I^(2)=81%)in patients with sepsis or septic shock.Moreover,there was no difference in other serious adverse events between patients who received clarithromycin and those in the control group(RR:1.02;95%CI:0.87-1.19;P=0.83;I^(2)=18%).Conclusion:Our meta-analysis did not reveal an improvement to short-term outcomes in patients with sepsis treated with clarithromycin.However,administration of clarithromycin did not increase the risk of adverse events.

关键词： Clarithromycin Meta-analysis Outcomes Sepsis Septic shock

Oxygen-defects evolution to stimulate continuous capacity increase in Co-free Li-rich layered oxides

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Journal of Energy Chemistry 2023年第7期82卷 259-267,I0006页

作者： Yibin Zhang xiaohui wen Zhepu Shi Bao Qiu Guoxin Chen Zhaoping Liu Ningbo Institute of Materials Technology and Engineering(NIMTE) Chinese Academy of Sciences(CAS)Ningbo 315201ZhejiangChina School of Materials Science and Chemical Engineering Ningbo UniversityNingbo 315201ZhejiangChina Department of Chemical and Environmental Engineering Faculty of Science and EngineeringUniversity of Nottingham Ningbo Chin1Ningbo 315199ZhejiangChina

Though oxygen defects are associated with deteriorated structures and aggravated cycling performance in traditional layered cathodes,the role of oxygen defects is still ambiguous in Li-rich layered oxides due to the involvement of oxygen redox.Herein,a Co-free Li-rich layered oxide Li_(1.286)Ni_(0.071)Mn_(0.643)O_(2)has been prepared by a co-precipitation method to systematically investigate the undefined effects of the oxygen defects.A significant O_(2)release and the propagation of oxygen vacancies were detected by operando differential electrochemical mass spectroscopy(DEMS)and electron energy loss spectroscopy(EELS),respectively.Scanning transmission electron microscopy-high angle annular dark field(STEMHAADF)reveals the oxygen vacancies fusing to nanovoids and monitors a stepwise electrochemical activation process of the large Li_(2)MnO_(3)domain upon cycling.Combined with the quantitative analysis conducted by the energy dispersive spectrometer(EDS),existed nano-scale oxygen defects actually expose more surface to the electrolyte for facilitating the electrochemical activation and subsequently increasing available capacity.Overall,this work persuasively elucidates the function of oxygen defects on oxygen redox in Co-free Li-rich layered oxides.

关键词： Li-rich layered oxide Irreversible oxygen loss Nano-scale oxygen defect Li_(2)MnO_(3)-domain activation

Genomic surveillance of emerging SARS-CoV-2 Omicron variations in Tianjin Municipality, China 2022

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Biosafety and Health 2024年第2期6卷 61-69页

作者： Xin Gao Ming Zou Yue Lei Zhaolin Tan Zhichao Zhuang Baolu Zheng Aiping Yu Yanzhen Han xiaohui Lu Xiaochang Liu Ying Wang Yuan Wang Liru Guo Guangwen Liu wen Li Yang Liu Likun Lv Peiyong Ning Xiaoyan Li Tianjin Centers for Disease Control and Prevention Tianjin 300011China Tianjin Key Laboratory of Pathogenic Microbiologyof Infectious Disease Tianjn Centers for Disease Controland PreventionTianjin 300011China

The coronavirus disease 2019(COvID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has severely impacted public health.In 2022,the Omicron variant of SARS-CoV-2 rapidly became the dominant circulating variant in the local COVID-19 outbreaks in Tianjin Municipality,China.To gain a deeper understanding of the genetic variations of the Omicron variant in Tianjin,specimens from indi-viduals who tested positive for SARS-CoV-2 between December 2021 and November 2022 were used for virus whole genome sequencing and phylogenetic analysis.A total of 1,674 high-quality Omicron sequences were obtained,consisting of 1,339 sequences from local cases belonging to 20 Phylogenetic Assignment of Named Global Outbreak(PANGO)lineages and 335 sequences from imported cases belonging to 70 lineages.Tianjin experienced five waves of local outbreaks,accompanied by multiple substitutions among subvariants,ranging from the initial BA.1.1 lineage to the subsequent BA.2,BF.7,and BA.5.2 lineages.The evolutionary rate of local strains,estimated to be 28.999 substitutions per year,and the evolutionary rate of imported strains,estimated to be 24.946 substitutions per year,were lower than that of the strains circulating globally.The addi-tional substitutions and deletions of local strains have been used to identify and disrupt the virus transmission chains.The subvariants such as BA.5.2.48,BA.5.2.49,BF.7.14,and XBB.1 circulating in the fifth epidemic wave presented criterial immune escape mutations including S:R346T,S:L452R and S:F486V.It is essential to implement genomic surveillance strategies to investigate further the development of genomic mutation char-acteristics in the SARS-CoV-2 variant.This ongoing monitoring will contribute to a better understanding of the virus's genetic changes and aid in effective control measures.

关键词： Severeacute respiratory syndrome coronavirus 2(SARS-CoV-2) Coronavirusdisease2019(COVID-19) Omicron variant Wholegenome sequencing(WGS)

Detection of cognitive impairment in patients with obstructive sleep apnea hypopnea syndrome using mismatch negativity

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Neural Regeneration Research 2012年第20期7卷 1591-1598页

作者： xiaohui wen Ningyu Wang Jinfeng Liu Zhanfeng Yan Zhonghai Xin Department of Otolaryngology Head & Neck Surgery Beijing Chaoyang Hospital Capital Medical University Beijing 100020 China Department of Otolaryngology Beijing Wangjing Hospital China Academy of Chinese Medical Sciences Beijing 100102 China

In this experiment, 97 patients with obstructive sleep apnea hypopnea syndrome were divided into three groups （mild, moderate, severe） according to minimum oxygen saturation, and 35 healthy subjects were examined as controls. Cognitive function was determined using the mismatch negativity paradigm and the Montreal Cognitive Assessment. The results revealed that as the disease worsened, the mismatch negativity latency was gradually extended, and the amplitude gradually declined in patients with obstructive sleep apnea hypopnea syndrome. Importantly, mismatch negativity latency in severe patients with a persistent time of minimum oxygen saturation 〈 60 seconds was significantly shorter than that with a persistent time of minimum oxygen saturation 〉 60 seconds. Correlation analysis revealed a negative correlation between minimum oxygen saturation latency and Montreal Cognitive Assessment scores. These findings indicate that intermittent night-time hypoxemia affects mismatch negativity waveforms and Montrea Cognitive Assessment scores. As indicators for detecting the cognitive functional status of obstructive sleep apnea hypopnea syndrome patients, the sensitivity of mismatch negativity is 82.93%, the specificity is 73.33%, the accuracy rate is 81.52%, the positive predictive value is 85.00%, the negative predictive value is 70.21%, the positive likelihood ratio is 3, and the negative likelihood ratio is 0.23. These results indicate that mismatch negativity can be used as an effective tool for diagnosis of cognitive dysfunction in obstructive sleep apnea hypopnea syndrome patients.

关键词： obstructive sleep apnea hypopnea syndrome mismatch negativity cognitive function MontrealCognitive Assessment latency diagnosis

基于GPU的北斗B1宽带复合信号实时发生器设计

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系统工程与电子技术 2024年第3期46卷 795-804页

作者：王子涵巴晓辉姜维蔡伯根王剑文韬北京交通大学电子信息工程学院北京100044 北京交通大学轨道交通控制与安全国家重点实验室北京100044 北京市电磁兼容与卫星导航工程技术研究中心北京100044 北京交通大学计算机与信息技术学院北京100044

为了实现北斗B1C+B1I信号的联合生成,提出一种基于软件无线电和图形处理器(graphics processing unit,GPU)加速的北斗B1宽带复合信号的实时生成方法,该方法针对单边带复数二进制偏移载波(single-sideband complex binary offset carrier... 详细信息

为了实现北斗B1C+B1I信号的联合生成,提出一种基于软件无线电和图形处理器(graphics processing unit,GPU)加速的北斗B1宽带复合信号的实时生成方法,该方法针对单边带复数二进制偏移载波(single-sideband complex binary offset carrier,SCBOC)调制方式的信号体制进行设计,系统根据用户配置的接收机运动轨迹和星历文件,生成中频信号并通过射频端发射。为了进一步提升GPU并行运算速度,从优化设备内存结构、设计并行线程架构和统一计算设备架构流(compute unified device architecture stream,CUDA)加速3个方面,设计了基于异步运算的加速采样点数据计算的CUDA优化实现方案。测试结果证明,优化后的算法可以基于SCBOC调制实时生成北斗B1I+B1C信号,基于GTX3060的GPU平台,信号90 M采样率下能实现8颗卫星复合信号的实时生成。

关键词： B1宽带复合信号软件无线电单边带复数二进制偏移载波调制统一计算设备架构流实时生成

Clinicoradiologic features of Mycoplasma pneumoniae bronchiolitis in children

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Pediatric Investigation 2018年第4期2卷 248-252页

作者： xiaohui wen Jinrong Liu Huimin Li Chengsong Zhao Shunying Zhao Department of Respiratory Medicine Beijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina

Importance: Acute Mycoplasma pneumoniae bronchiolitis can progress into bronchiolitis obliterans (BO) in children, which has a major influence on a child's quality of life and is associated with M. pneumoniae bronchiolitis. Early identification and treatment of M. pneumoniae bronchiolitis is important to prevent the development of BO. Objective: To enhance the understanding of the diagnosis and treatment of M. pneumoniae bronchiolitis in children. Methods: Eight patients with M. pneumoniae bronchiolitis were retrospectively analyzed. results: Five of the patients with M. pneumoniae bronchiolitis were male and three of them were female. All patients suffered from fever and cough. Moist rales and wheezing were noted in both lungs in six patients. High-resolution computed tomography of the chest showed bronchiolitis in all patients, with large airway injury in two and focal bronchopneumonia in six. Two patients were confirmed to have asthma. Seven patients had personal and/or family histories of atopic diseases. Allergen testing was performed in six patients, which produced positive results in four;the remaining two patients had negative results, but their total IgE levels were > 200 IU/ml. Azithromycin therapy and glucocorticoid therapy was administered to all eight patients. One patient required noninvasive ventilation. Treatment of all patients was successful, with no development of bronchiolitis obliterans during the 4- to 8-month follow-up. Interpretation: Mycoplasma pneumoniae bronchiolitis can occur in children, especially in atopic individuals. The use, time of initiation, and effects of glucocorticoids administration in these patients for the prevention of BO require further investigation.

关键词： Mycoplasma pneumoniae Bronchiolitis Glucocorticoid Bronchiolitis obliterans

X射线成像用零维无铅杂化卤化物闪烁体研究进展(特邀)

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激光与光电子学进展 2024年第3期61卷 331-347页

作者：李雯李云云迟晓慧吴云涛中国科学院上海硅酸盐研究所人工晶体研究中心上海201899 强脉冲辐射环境模拟与效应国家重点实验室陕西西安710024

X射线闪烁体在医疗诊断、安全检查、工业无损探测等领域应用广泛。近十年来,零维结构有机-无机杂化金属卤化物因具有非潮解、高稳定性、无自吸收、高荧光量子效率等优异的物理性质和发光性能,在X射线成像领域逐渐受到关注并已展现出极... 详细信息

X射线闪烁体在医疗诊断、安全检查、工业无损探测等领域应用广泛。近十年来,零维结构有机-无机杂化金属卤化物因具有非潮解、高稳定性、无自吸收、高荧光量子效率等优异的物理性质和发光性能,在X射线成像领域逐渐受到关注并已展现出极大的应用潜力。本文将概述X射线闪烁体的基本探测原理和关键探测性能参数,介绍最具代表性的零维锰基、锡基、锑基和铜基卤化物闪烁体在X射线成像领域的研究进展,并展望此类零维杂化材料的未来发展方向。

关键词：零维结构杂化金属卤化物无铅卤化物闪烁体光致发光辐照发光 X射线探测 X射线成像

Local inhibition of GABA affects precedence effect in the inferior colliculus

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Neural Regeneration Research 2014年第4期9卷 420-429页

作者： Yanjun Wang Ningyu Wang Dan Wang Jun Jia Jinfeng Liu Yan Xie xiaohui wen Xiaoting Li Department of Otorhinolaryngology Head and Neck Surgery Beijing Chaoyang HospitalCapital Medical University Department of Neurophysiology Capital Medical University

The precedence effect is a prerequisite for faithful sound localization in a complex auditory environment, and is a physiological phenomenon in which the auditory system selectively suppresses the directional information from echoes. Here we investigated how neurons in the inferior colliculus respond to the paired sounds that produce precedence-effect illusions, and whether their firing behavior can be modulated through inhibition with gamma-aminobutyric acid （GABA）. We recorded extracellularly from 36 neurons in rat inferior colliculus under three conditions： no injection, injection with saline, and injection with gamma-aminobutyric acid. The paired sounds that produced precedence effects were two identical 4-ms noise bursts, which were delivered contralaterally or ipsilaterally to the recording site. The normalized neural responses were measured as a function of different inter-stimulus delays and half-maximal interstimulus delays were acquired. Neuronal responses to the lagging sounds were weak when the inter-stimulus delay was short, but increased gradually as the delay was lengthened. Saline injection produced no changes in neural responses, but after local gamma-arninobutyric acid application, responses to the lagging stimulus were suppressed. Application of gamma-aminobutyric acid affected the normalized response to lagging sounds, independently of whether they or the paired sounds were contralateral or ipsilateral to the recording site. These observations suggest that local inhibition by gamma-aminobutyric acid in the rat inferior colliculus shapes the neural responses to lagging sounds, and modulates the precedence effect.

关键词： nerve regeneration precedence effect auditory center inferior colliculus gamma-amino-butyric acid local inhibition echo suppression lagging stimulus NSFC grant neural regeneration