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Automated robot and artificial intelligence-powered wastewater surveillance for proactive mpox outbreak prediction 机器人和人工智能驱动的废水自动监测,用于猴痘疫情的主动预测
IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-08-01 DOI: 10.1016/j.bsheal.2024.07.002
Guanyong Ou , Yuxuan Tang , Jiexiang Liu , Yabin Hao , Zhi Chen , Ting Huang , Shaxi Li , Shiyu Niu , Yun Peng , Jiaqi Feng , Hongwei Tu , Yang Yang , Han Zhang , Yingxia Liu

In the wake of the largest-ever recorded outbreak of mpox in terms of magnitude and geographical spread in human history since May 2022, we innovatively developed an automated online sewage virus enrichment and concentration robot for disease tracking. Coupled with an artificial intelligence (AI) model, our research aims to estimate mpox cases based on the concentration of the monkeypox virus (MPXV) in wastewater. Our research has revealed a compelling link between the levels of MPXV in wastewater and the number of clinically confirmed mpox infections, a finding that is reinforced by the ability of our AI prediction model to forecast cases with remarkable precision, capturing 87 % of the data’s variability. However, it is worth noting that this high precision in predictions may be related to the relatively high frequency of data acquisition and the relatively non-mobile isolated environment of the hospital itself. In conclusion, this study represents a significant step forward in our ability to track and respond to mpox outbreaks. It has the potential to revolutionize public health surveillance by utilizing innovative technologies for disease surveillance and prediction.

自2022年5月以来,人类历史上爆发了规模最大、地域传播范围最广的猴痘疫情,为此,我们创新性地开发了一种用于疫情追踪的在线自动污水病毒富集和浓缩机器人。结合人工智能(AI)模型,我们的研究旨在根据污水中猴痘病毒(MPXV)的浓度来估计痘病例。我们的研究发现,废水中的猴痘病毒浓度与临床确诊的猴痘感染病例数量之间存在着令人信服的联系,而我们的人工智能预测模型能够非常精确地预测病例,捕捉到了数据变化的 87%,从而进一步证实了这一发现。不过,值得注意的是,这种高精度预测可能与数据采集频率相对较高以及医院本身相对非流动的隔离环境有关。总之,这项研究标志着我们在跟踪和应对麻痘爆发的能力方面向前迈出了重要一步。通过利用创新技术进行疾病监测和预测,它有可能彻底改变公共卫生监测。
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引用次数: 0
Cyberbiosecurity: Advancements in DNA-based information security 网络生物安全:基于 DNA 的信息安全进展
IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-08-01 DOI: 10.1016/j.bsheal.2024.06.002
Tuoyu Liu , Sijie Zhou , Tao Wang , Yue Teng

Synthetic biology is a crucial component of the “cyber-biological revolution” in this new industrial revolution. Owing to breakthroughs in synthetic biology, deoxyribonucleic acid (DNA), the storehouse of hereditary material in biological systems, can now be used as a medium for storage (synthesis) and reading (sequencing) of information. However, integrating synthetic biology with computerization has also caused cyberbiosecurity concerns, encompassing biosecurity and information security issues. Malicious codes intended to attack computer systems can be stored as artificially synthesized DNA fragments, which can be released during DNA sequencing and decoding and attack computer and network systems. As these cyberbiosecurity threats become increasingly realistic, spreading awareness and information about how they can be prevented and controlled is crucial. This review aims to address this need by offering crucial theoretical backing for cyberbiosecurity research and raising awareness of risk mitigation and control measures in information security, biosecurity, and national security.

合成生物学是新工业革命中 "网络生物革命 "的重要组成部分。由于合成生物学取得了突破性进展,生物系统中遗传物质的储存库--脱氧核糖核酸(DNA)现在可以作为信息存储(合成)和读取(测序)的媒介。然而,合成生物学与计算机化的结合也引发了网络生物安全问题,包括生物安全和信息安全问题。旨在攻击计算机系统的恶意代码可以存储为人工合成的 DNA 片段,在 DNA 测序和解码过程中释放出来,攻击计算机和网络系统。随着这些网络生物安全威胁变得越来越现实,传播如何预防和控制这些威胁的意识和信息至关重要。本综述旨在满足这一需求,为网络生物安全研究提供重要的理论支持,并提高人们对信息安全、生物安全和国家安全领域风险缓解和控制措施的认识。
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引用次数: 0
An online survey among convalescents 5 months post SARS-CoV-2 infection in China 对中国 SARS-CoV-2 感染后 5 个月康复者的在线调查
IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-08-01 DOI: 10.1016/j.bsheal.2024.06.001

The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection persist months and years after recovery. We conducted an online survey to assess the health condition of convalescents approximately 5 months following the primary infection of SARS-CoV-2. The study recruited 5,510 individuals who were primary infected, 626 participants who had experienced reinfection, and 521 participants who were without infective history. The most common disorders after the primary infection group were fatigue (15.18 %), memory issue (13.13 %), post-exertional malaise (PEM, 11.68 %), and brain fog (11.29 %) at the time of survey. In addition, SARS-CoV-2 infection had an impact on the reproductive systems. In stepwise logistic regression analysis, smoking currently, with background diseases, and outpatient visits in the acute phase could be associated with moderate / severe disorders. Further analysis of different background diseases showed that allergic rhinitis, hyperlipidemia, cardiovascular disease, autoimmune diseases, neurological diseases, and asthma likely increased the risk of moderate/severe disorders. The probability of developing disorders of individuals with SARS-CoV-2 reinfection was higher before the secondary infection than uninfected people. Fatigue, PEM, muscle pain/spasms, chills, joint pain, excessive sweating at rest, headache / dizziness, sore throat or foreign body sensation in the throat, cough, expectoration, dry / painful / watery eyes, loss of appetite and constipation were associated with an increased risk of reinfection. It was essential to undertake further research with enhanced randomization in a larger sample in the community, and to strengthen the validation of the research conclusions. The findings of this study contribute to a deeper understanding of the health recovery process among coronavirus disease 2019 (COVID-19) convalescents. Moreover, the findings help identify characteristic health risk factors associated with convalescents and highlight the risk of moderate / severe disorders and reinfection. Furthermore, the findings also provide valuable guidance and reference for SARS-CoV-2 rehabilitation strategies and the prevention of reinfection, offering insights for scientific recommendations.

严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)感染的影响在康复后数月甚至数年仍然存在。我们进行了一项在线调查,以评估初次感染 SARS-CoV-2 约 5 个月后康复者的健康状况。研究共招募了 5,510 名初次感染者、626 名再次感染者和 521 名无感染史者。在调查时,原发感染组最常见的疾病是疲劳(15.18%)、记忆问题(13.13%)、劳累后不适(PEM,11.68%)和脑雾(11.29%)。此外,SARS-CoV-2 感染对生殖系统也有影响。在逐步逻辑回归分析中,目前吸烟、患有背景疾病和急性期门诊就诊可能与中度/重度失调有关。对不同背景疾病的进一步分析表明,过敏性鼻炎、高脂血症、心血管疾病、自身免疫性疾病、神经系统疾病和哮喘可能会增加中度/重度失调的风险。与未感染者相比,SARS-CoV-2 再感染者在二次感染前发生疾病的概率更高。疲倦、心悸、肌肉疼痛/痉挛、发冷、关节痛、休息时出汗过多、头痛/头晕、喉咙痛或喉咙有异物感、咳嗽、痰多、眼睛干涩/疼痛/流泪、食欲不振和便秘与再感染风险增加有关。有必要在更大的社区样本中加强随机化,开展进一步研究,并加强对研究结论的验证。本研究的结果有助于加深对 2019 年冠状病毒病(COVID-19)康复者健康恢复过程的理解。此外,研究结果还有助于确定与康复者相关的特征性健康风险因素,并强调中度/重度失调和再感染的风险。此外,研究结果还为SARS-CoV-2康复策略和预防再感染提供了有价值的指导和参考,为科学建议提供了启示。
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引用次数: 0
The differential effects of integrase strand transfer inhibitors and efavirenz on neuropsychiatric conditions and brain imaging in HIV-positive men who have sex with men 整合酶链转移抑制剂和依非韦伦对艾滋病毒阳性男男性行为者神经精神状况和脑成像的不同影响
IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-08-01 DOI: 10.1016/j.bsheal.2024.07.001
Yihui He , Yang Zhang , Jiaxin Zhen , Guangqiang Sun , Zhen Li , Bo Yang , Bin Yang , Keyi Chang , Xue Chen , Yulin Zhang , Caiping Guo , Wen Wang , Ping Wu , Tong Zhang , Lei Wang

Integrase strand transfer inhibitors (INSTIs) have emerged as the first-line choice for treating human immunodeficiency virus (HIV) infection due to their superior efficacy and safety. However, the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV (PLWH) is not fully understood due to limited data. In this study, we conducted a cross-sectional examination of PLWH receiving antiretroviral therapy, with a specific focus on HIV-positive men who have sex with men (MSM) on INSTI-based regimens (n = 61) and efavirenz (EFV)-based regimens (n = 28). Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging (MRI) scans, including T1-weighted images and resting-state functional MRI. Compared to the EFV group, the INSTI group exhibited primarily reduced gray matter volume (GMV) in the right superior parietal gyrus, higher regional homogeneity (ReHo) in the left postcentral gyrus, lower ReHo in the right orbital part of the inferior frontal gyrus, and increased voxel-wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus. Furthermore, the analysis revealed a main effect of antiretroviral drugs on GMV changes, but no main effect of neuropsychiatric disorders or their interaction. The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group, validating the initial findings. Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI-based regimens compared to those on EFV-based regimens. These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI-based regimens.

整合酶链转移抑制剂(INSTIs)因其卓越的疗效和安全性,已成为治疗人类免疫缺陷病毒(HIV)感染的一线选择。然而,由于数据有限,INSTIs 对艾滋病病毒感染者(PLWH)神经精神疾病发展的影响尚不完全清楚。在本研究中,我们对接受抗逆转录病毒治疗的艾滋病感染者进行了横断面检查,重点关注接受 INSTI 治疗方案(n = 61)和依非韦伦(EFV)治疗方案(n = 28)的艾滋病阳性男男性行为者(MSM)。参与者接受了全面的神经精神评估和多模态磁共振成像(MRI)扫描,包括T1加权图像和静息态功能磁共振成像。与 EFV 组相比,INSTI 组主要表现出右侧顶叶上回灰质体积(GMV)减少,左侧中央后回区域同质性(ReHo)提高,右侧额叶下回眶部 ReHo 降低,左侧颞下回种子区与右侧楔状回集群的体素功能连接性增强。此外,分析显示抗逆转录病毒药物对 GMV 变化有主效应,但神经精神疾病或它们之间的交互作用没有主效应。对未更换治疗方案的参与者进行的重复分析证实了 INSTI 组的 GMV 变化,从而验证了最初的研究结果。我们的研究表明,与使用 EFV 治疗方案的 PLWH 相比,使用 INSTI 治疗方案的 PLWH 脑灰质萎缩,脑功能发生变化。这些神经影像学结果为了解接受 INSTI 治疗方案的 PLWH 脑网络改变的特征提供了宝贵的见解。
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引用次数: 0
A secure visualization platform for pathogenic genome analysis with an accurate reference database 利用精确参考数据库进行病原体基因组分析的安全可视化平台
IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-08-01 DOI: 10.1016/j.bsheal.2024.07.003
Guomei Fan , Chongye Guo , Qian Zhang , Dongmei Liu , Qinglan Sun , Zhigang Cui , Haijian Zhou , Yuanchun Zhou , Zhibin Guo , Juncai Ma , Linhuan Wu

Investigating the genetic and developmental characteristics, infection transmission attributes, and epidemiological trends of pathogens using genomic data represents the foundation for pathogen surveillance and is a crucial prerequisite for guaranteeing global health security. To meet the analytical demands of research relating to pathogen prevention and control, we designed a secure visualization system capable of pathogen genome assembly, annotation, species identification, sequence typing, antibiotic resistance and virulence analysis, genomic mobile element and transferable resistance gene annotation, and phylogenetic tree reconstruction. For highly pathogenic organisms requiring complete data protection, we have developed a secure computing tool that utilizes a trusted execution environment, is combined with blockchain and privacy computing technologies, and is specifically designed for nucleotide basic local alignment search tool (BLASTn) comparison analysis. This technological advancement offers scientific support for in-depth investigations into pathogen transmission and epidemiological mechanisms, environmental adaptability, evolutionary trends, and immune evasion mechanisms, as well as the identification of new or emerging pathogen strains. This, in turn, aids efforts in infectious disease prevention, treatment, and research.

利用基因组数据调查病原体的遗传和发育特征、感染传播属性和流行趋势是病原体监测的基础,也是保障全球健康安全的重要前提。为了满足病原体防控研究的分析需求,我们设计了一套安全的可视化系统,能够进行病原体基因组组装、注释、物种鉴定、序列分型、抗生素耐药性和毒力分析、基因组移动元件和可转移耐药基因注释以及系统发生树重建。针对需要全面数据保护的高致病性生物,我们开发了一种安全计算工具,利用可信执行环境,结合区块链和隐私计算技术,专门用于核苷酸基本局部比对搜索工具(BLASTn)比对分析。这一技术进步为深入研究病原体传播和流行病学机制、环境适应性、进化趋势和免疫逃避机制以及识别新的或新出现的病原体菌株提供了科学支持。这反过来又有助于传染病的预防、治疗和研究工作。
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引用次数: 0
Evaluation of antibody responses in healthy individuals receiving SARS-CoV-2 inactivated vaccines 评估接种 SARS-CoV-2 灭活疫苗的健康人的抗体反应
IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-06-01 DOI: 10.1016/j.bsheal.2024.04.001
Ziyu Liu , Liyan Cai , Man Xing , Nan Qiao , Jiaojiao Liu , Xuejun Li , Chiyu Zhang , Naijun Tang , Zhelong Xu , Yingying Guo , Renfei Lu , Dongming Zhou

Inactivated coronavirus disease 2019 (COVID-19) vaccines such as CoronaVac and BBIBP-CorV have been widely used in China. However, more investigation is still needed to understand antibodies' duration and effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the real world. In this study, 575 participants who had been vaccinated with two or three doses of the inactivated vaccine were recruited. Serum samples were collected and tested for anti-spike IgG and neutralizing antibodies against SARS-CoV-2 (original strain, Dela, and Omicron). Unsurprisingly, a third dose of the vaccine significantly enhanced antibody responses against SARS-CoV-2 and its variants. However, despite a booster dose, the neutralizing antibody levels against Omicron, particularly the BA.5.2 subvariant, remained low. There was no sex bias, but an age bias was observed. Notably, the predominant IgG subclass antibodies were IgG1 and IgG2, with a much lower level of IgG4. After the booster shot, the ratio of IgG4 to IgG1 significantly increased. The observation of IgG1 to the IgG4 class switch after repeated inactivated vaccinations underscores the importance of continuous monitoring of subclass antibody responses. Further clinical investigations are required to understand the implications of this class switch for optimizing immunization strategies.

冠状病毒病2019(COVID-19)灭活疫苗(如CoronaVac和BBIBP-CorV)已在中国广泛使用。然而,要了解在现实世界中抗体对严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2)变种的持续时间和有效性,还需要进行更多的调查。在这项研究中,共招募了 575 名接种过两剂或三剂灭活疫苗的参与者。研究人员收集了血清样本,并对其进行了抗尖峰抗体 IgG 和抗 SARS-CoV-2(原始株、德拉株和 Omicron 株)中和抗体的检测。不出所料,第三剂疫苗显著增强了对 SARS-CoV-2 及其变种的抗体反应。然而,尽管注射了一剂加强剂,针对 Omicron(尤其是 BA.5.2 亚变异株)的中和抗体水平仍然很低。没有性别偏差,但观察到年龄偏差。值得注意的是,主要的 IgG 亚类抗体是 IgG1 和 IgG2,IgG4 的水平要低得多。注射加强针后,IgG4 与 IgG1 的比例明显增加。在反复接种灭活疫苗后观察到 IgG1 向 IgG4 的转变,这强调了持续监测亚类抗体反应的重要性。要了解这种类别转换对优化免疫策略的影响,还需要进一步的临床研究。
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引用次数: 0
Advances in technology for the laboratory diagnosis of individuals with HIV/AIDS coinfected with Mycobacterium tuberculosis 实验室诊断合并感染结核分枝杆菌的艾滋病毒/艾滋病患者的技术进展
IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-06-01 DOI: 10.1016/j.bsheal.2024.04.003
Jin Sun , Xiaoxu Han , Hongxia Yan , Xin Zhang , Taiyi Jiang , Tong Zhang , Hao Wu , Grigory Kaminskiy , Yingmin Ma , Eduard Karamov , Bin Su

The high morbidity and mortality rate of individuals with human immunodeficiency virus (HIV) / acquired immunodeficiency syndrome (AIDS) coinfected with Mycobacterium tuberculosis (MTB) is a tough challenge for current global tuberculosis prevention and control efforts. HIV/MTB coinfection is more complex than a single infection, and the interaction between the two diseases aggravates the deterioration caused by the disease, resulting in increased hospitalizations and deaths. Rapid screening and early diagnosis facilitate the timely initiation of anti-tuberculosis treatment in HIV/MTB coinfected individuals, thereby reducing transmission and the incidence of adverse prognoses. To date, pathogenic detection has remained the gold standard for diagnosing tuberculosis, but its sensitivity and specificity are greatly affected by the body's immune status, which limits its application in the diagnosis of HIV/MTB coinfection. Recently, immunology and molecular detection technology has developed rapidly. New detection technologies, such as interferon-γ release assays, interferon-gamma inducible protein 10, and GeneXpert MTB/RIF assay have overcome the limitations of traditional detection methods, significantly improved the sensitivity and specificity of tuberculosis diagnosis, and brought new hope to the detection of HIV/MTB coinfection. In this article, the principle, scope of application, and latest research progress of relevant detection methods are reviewed to provide a reference for the early diagnosis of HIV/MTB coinfection.

人类免疫缺陷病毒(HIV)/获得性免疫缺陷综合征(AIDS)合并感染结核分枝杆菌(MTB)的患者发病率和死亡率都很高,这对当前全球结核病防控工作是一个严峻的挑战。艾滋病病毒/结核分枝杆菌合并感染比单一感染更为复杂,两种疾病的相互作用加剧了疾病的恶化,导致住院和死亡人数增加。快速筛查和早期诊断有助于对艾滋病毒/结核病合并感染者及时启动抗结核治疗,从而减少传播和不良预后的发生。迄今为止,病原体检测仍是诊断结核病的金标准,但其灵敏度和特异性受人体免疫状态的影响很大,这限制了其在艾滋病毒/结核病合并感染诊断中的应用。近年来,免疫学和分子检测技术发展迅速。干扰素-γ释放测定、干扰素-γ诱导蛋白10、GeneXpert MTB/RIF测定等新型检测技术克服了传统检测方法的局限性,显著提高了结核病诊断的灵敏度和特异性,为HIV/MTB合并感染的检测带来了新的希望。本文综述了相关检测方法的原理、应用范围和最新研究进展,为 HIV/MTB 合并感染的早期诊断提供参考。
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引用次数: 0
A novel method to assess antibody-dependent cell-mediated cytotoxicity against influenza A virus M2 in immunized murine models 在免疫小鼠模型中评估抗甲型流感病毒 M2 的抗体依赖性细胞介导细胞毒性的新方法
IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-06-01 DOI: 10.1016/j.bsheal.2024.04.002
Yinjie Liang , Junjia Guo , Zhen Li , Shiyuan Liu , Ting Zhang , Shucai Sun , Funa Lu , Yuqian Zhai , Wenling Wang , Chuanyi Ning , Wenjie Tan

The matrix protein 2 (M2) is a preferred target for developing a universal vaccine against the influenza A virus (IAV). This study aimed to develop a method for assessing antibody-dependent cell-mediated cytotoxicity (ADCC) associated with M2-based immunization in mice. We first established a stable cell line derived from mouse lymphoma cells (YAC-1) expressing M2 of H3N2. This cell line, designated as YAC-1-M2, was generated using a second-generation lentiviral tricistronic plasmid system to transduce the M2 gene into YAC-1 cells. The ADCC effect induced by polyclonal antibodies targeting matrix protein 2 ectodomain (M2e) was demonstrated by YAC-1-M2 cell lysis by natural killer cells (NK) derived from mice, in the presence of anti-M2 antibodies obtained from mice immunized with an mRNA vaccine based on M2e. This ADCC effect was found to be stronger compared to the effect induced by monoclonal antibodies (14C2) against M2. Moreover, the ADCC effect was enhanced as the effector-to-target ratio of NK to YAC-1-M2 cells increased. In conclusion, we established a novel method to detect ADCC of M2 of IAV, which paves the way for the development of an M2-based universal vaccine against IAV and an in-depth analysis of its mechanism of broad-spectrum immune protection in mice.

基质蛋白2(M2)是开发甲型流感病毒(IAV)通用疫苗的首选靶标。本研究旨在开发一种方法,用于评估与基于 M2 的小鼠免疫相关的抗体依赖性细胞介导的细胞毒性(ADCC)。我们首先建立了一个稳定的细胞系,该细胞系来源于表达 H3N2 M2 的小鼠淋巴瘤细胞(YAC-1)。这种细胞系被命名为 YAC-1-M2,是利用第二代慢病毒三链式质粒系统将 M2 基因转入 YAC-1 细胞中产生的。靶向基质蛋白 2 外结构域(M2e)的多克隆抗体诱导的 ADCC 效应通过小鼠自然杀伤细胞(NK)对 YAC-1-M2 细胞的裂解得到了证实。与针对 M2 的单克隆抗体(14C2)诱导的效果相比,这种 ADCC 效果更强。此外,随着 NK 与 YAC-1-M2 细胞的效应目标比的增加,ADCC 效应也会增强。总之,我们建立了一种检测 IAV M2 ADCC 的新方法,这为开发基于 M2 的通用 IAV 疫苗以及深入分析其在小鼠中的广谱免疫保护机制铺平了道路。
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引用次数: 0
Impact of ursodeoxycholic acid therapy in autoimmune liver disease patients with COVID-19 and its clinical prognosis 熊去氧胆酸治疗对 COVID-19 自身免疫性肝病患者的影响及其临床预后
IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-06-01 DOI: 10.1016/j.bsheal.2024.04.004
Minghui Li , Weihua Cao , Tingting Jiang , Wen Deng , Shiyu Wang , Shuling Wu , Lu Zhang , Yao Lu , Min Chang , Ruyu Liu , Xiaoyan Ding , Ge Shen , Yuanjiao Gao , Hongxiao Hao , Xiaoxue Chen , Leiping Hu , Mengjiao Xu , Yuyong Jiang , Wei Yi , Yao Xie , Rui Song

To explore the impact of ursodeoxycholic acid (UDCA) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and clinical outcomes in patients with autoimmune liver disease (AILD). Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment. Relevant data were collected regarding AILD diagnosis, treatment, biochemical indicators, and imaging examination. The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed. A total of 1,138 patients completed follow-up. The usage rate of hormone (P = 0.003) and immunosuppressant (P = 0.001) used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group. The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients (P = 0.003). The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group (P = 0.018). Logistic regression analysis showed that UDCA use (P = 0.003) was correlated to a lower incidence of SARS-CoV-2, while immunosuppressant use (P = 0.017) increased the incidence. Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group (P = 0.018). UDCA is associated with low SARS-CoV-2 incidence in AILD patients, while immunosuppressant increases its incidence instead. Patients receiving UDCA treatment have a longer recovery time after being infected.

目的:探讨熊去氧胆酸(UDCA)对自身免疫性肝病(AILD)患者严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2)感染和临床预后的影响。研究人员招募了确诊为自身免疫性肝病(AILD)的患者,并根据他们是否接受 UDCA 治疗将其分为 UDCA 组和非 UDCA 组。收集了有关 AILD 诊断、治疗、生化指标和影像学检查的相关数据。观察 AILD 患者的 SARS-CoV-2 感染率和预后。共有 1 138 名患者完成了随访。非 UDCA 组用于治疗 AILD 的激素(P = 0.003)和免疫抑制剂(P = 0.001)的使用率明显低于 UDCA 组。感染 SARS-CoV-2 的患者使用 UDCA 的比例明显低于未感染患者(P = 0.003)。非 UDCA 组的 SARS-CoV-2 感染率明显高于 UDCA 组(P = 0.018)。逻辑回归分析显示,使用 UDCA(P = 0.003)与较低的 SARS-CoV-2 感染率相关,而使用免疫抑制剂(P = 0.017)则会增加感染率。接受 UDCA 治疗的患者从 SARS-CoV-2 感染中恢复的时间明显长于未接受 UDCA 治疗的患者(P = 0.018)。UDCA 可降低 AILD 患者的 SARS-CoV-2 感染率,而免疫抑制剂反而会增加感染率。接受 UDCA 治疗的患者在感染后的恢复时间更长。
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引用次数: 0
Caspase-8 activation regulates enterovirus D68 infection-induced inflammatory response and cell death Caspase-8 激活调控肠道病毒 D68 感染诱发的炎症反应和细胞死亡
IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-06-01 DOI: 10.1016/j.bsheal.2024.03.003
Yuanyuan Zhou , Chongtao Zhang , Yuhan Zhang , Fei Li , Jun Shen

Enterovirus D68 (EV-D68) infection causes severe acute respiratory infection and severe neurological complications, such as acute flaccid myelitis (AFM), in children. However, although EV-D68 has pandemic potential, no effective drugs or vaccines are currently clinically available. Furthermore, EV-D68 infection-induced inflammatory response and cell death are not fully understood. In this study, we demonstrated that several inflammatory cytokines were upregulated in a multiplicity of infection (MOI) dependent manner in EV-D68-infected human rhabdomyosarcoma (RD) cells. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) confirmed that tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand-5 (CCL-5), and CXC motif chemokine ligand-5 (CXCL-5) mRNA levels were highly upregulated after EV-D68 infection. IL-1β processing and maturation mediated by caspase-8 was inhibited by the caspase-8 inhibitor Z-IETD-FMK. EV-D68 infection activates caspase-8 to mediate IL-1β maturation and secretion. Additionally, EV-D68 activated cell death-related proteins such as caspase-3, poly (ADP-ribose) polymerase 1 (PARP-1), phosphorylation of Mixed Lineage Kinase domain-like protein (pMLKL), and gasdermin E (GSDME). Thus, EV-D68 infection activates caspase-8, which triggers the necroptosis and apoptosis pathways. Overall, our data suggest that caspase-8 activation is associated with the inflammatory response and cell death in EV-D68-infected RD cells. This mechanism represents a novel target for the treatment of EV-D68 infection by inhibiting caspase-8 activation.

肠道病毒 D68(EV-D68)感染会导致儿童严重的急性呼吸道感染和严重的神经系统并发症,如急性弛缓性脊髓炎(AFM)。然而,尽管 EV-D68 有可能大流行,但目前临床上还没有有效的药物或疫苗。此外,EV-D68 感染诱导的炎症反应和细胞死亡尚未完全明了。在这项研究中,我们证实了在 EV-D68 感染的人横纹肌肉瘤(RD)细胞中,几种炎症细胞因子以依赖感染倍数(MOI)的方式上调。定量逆转录酶聚合酶链反应(qRT-PCR)证实,EV-D68感染后,肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)、C-C马达趋化因子配体-5(CCL-5)和CXC马达趋化因子配体-5(CXCL-5)的mRNA水平高度上调。Caspase-8抑制剂Z-IETD-FMK抑制了Caspase-8介导的IL-1β加工和成熟。EV-D68感染激活了caspase-8,从而介导了IL-1β的成熟和分泌。此外,EV-D68 还激活了与细胞死亡相关的蛋白,如 caspase-3、多聚(ADP-核糖)聚合酶 1(PARP-1)、混合系激酶域样蛋白磷酸化(pMLKL)和 gasdermin E(GSDME)。因此,EV-D68 感染会激活 caspase-8,从而触发坏死和凋亡途径。总之,我们的数据表明,caspase-8 的激活与 EV-D68 感染的 RD 细胞的炎症反应和细胞死亡有关。这一机制代表了通过抑制 caspase-8 活化来治疗 EV-D68 感染的新靶点。
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