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Rapid adaptive substitution of L226Q in HA protein increases the pathogenicity of H9N2 viruses in mice HA 蛋白中 L226Q 的快速适应性替代增加了 H9N2 病毒对小鼠的致病性
Pub Date : 2024-03-01 DOI: 10.1016/j.imj.2024.100090
Min Tan , Ye Zhang , Hong Bo , Xiyan Li , Shumei Zou , Lei Yang , Jia Liu , Qi Chen , Xiaohao Xu , Wenfei Zhu , Dayan Wang

Background

Since the first human infection with H9N2 virus was reported in 1998, the number of cases of H9N2 infection has exceeded one hundred by 2021. However, there is no systematic description of the biological characteristics of H9N2 viruses isolated from humans.

Methods

Therefore, this study analyzed the pathogenicity in mice of all available H9N2 viruses isolated from human cases in China from 2013 to 2021.

Results

Although most of the H9N2 viruses analyzed showed low or no pathogenicity in mice, the leucine to glutamine substitution at residue 226 (L226Q) in the hemagglutinin (HA) protein rapidly emerged during the adaptation of H9N2 viruses, and was responsible for severe infections and even fatalities. HA amino acid 226Q conferred a remarkable competitive advantage on H9N2 viruses in mice relative to viruses containing 226L, increasing their virulence, infectivity, and replication.

Conclusion

Thus, our study demonstrates that the adaptive substitution HA L226Q rapidly acquired by H9N2 viruses during the course of infection in mice contributed to their high pathogenicity.

背景自 1998 年首次报告人类感染 H9N2 病毒以来,到 2021 年,H9N2 感染病例已超过 100 例。方法因此,本研究分析了 2013 年至 2021 年中国从人类病例中分离的所有 H9N2 病毒在小鼠中的致病性。结果尽管所分析的大多数 H9N2 病毒在小鼠中表现出低致病性或无致病性,但在 H9N2 病毒的适应过程中,血凝素(HA)蛋白中第 226 位残基的亮氨酸到谷氨酰胺的置换(L226Q)迅速出现,并导致严重感染甚至死亡。与含有 226L 的病毒相比,HA 氨基酸 226Q 使小鼠体内的 H9N2 病毒具有显著的竞争优势,增强了其毒力、感染性和复制能力。
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引用次数: 0
Viremia and clinical manifestations in acute febrile patients of Chikungunya infection during the 2016 CHIKV outbreak in Delhi, India 2016年印度德里CHIKV疫情期间基孔肯雅病毒感染急性发热患者的病毒血症和临床表现
Pub Date : 2024-03-01 DOI: 10.1016/j.imj.2024.100088
Rohit Sagar , Siva Raghavendhar , Vineet Jain , Naushad Khan , Anmol Chandele , Ashok Kumar Patel , Murali Kaja , Pratima Ray , Neera Kapoor

Background

Chikungunya virus (CHIKV) is an infectious agent that caused several outbreaks among different countries and affected approximately 1.3 million Indian populations. It is transmitted by Aedes mosquito–either A. albopictus or A. aegypti. Generally, the clinical manifestations of CHIKV infection involve high-grade fever, joint pain, skin rashes, headache, and myalgia. The present study aims to investigate the relationship between the CHIKV virus load and clinical symptoms of the CHIKV infection so that better patient management can be done in the background of the CHIKV outbreak as there is no licensed anti-viral drug and approved vaccines available against CHIKV.

Methods

CHIKV RTPCR positive samples (n = 18) (Acute febrile patients having D.O.F ≤ 7 days) were taken for the quantification of CHIKV viremia by Real-Time PCR. Clinical features of the febrile patients were recorded during the collection of blood samples.

Results

The log mean virus load of 18 RT-PCR-positive samples was 1.3 × 106 copies/mL (1.21 × 103–2.33 × 108 copies/mL). Among the observed clinical features, the log mean virus load (CHIKV) of the patients without skin rash is higher than in the patients with skin rash (6.61 vs 5.5, P = 0.0435).

Conclusion

The conclusion of the study was that the patients with skin rashes had lower viral load and those without skin rashes had higher viral load.

背景基孔肯雅病毒(CHIKV)是一种传染性病原体,曾在不同国家多次爆发,影响了约 130 万印度人。它由白纹伊蚊或埃及伊蚊传播。一般来说,CHIKV 感染的临床表现包括高烧、关节痛、皮疹、头痛和肌痛。本研究旨在探讨CHIKV病毒载量与CHIKV感染的临床症状之间的关系,以便在CHIKV疫情爆发的背景下更好地管理患者,因为目前还没有针对CHIKV的许可抗病毒药物和批准疫苗。结果 18 份 RT-PCR 阳性样本的病毒载量对数平均值为 1.3 × 106 拷贝/毫升(1.21 × 103-2.33 × 108 拷贝/毫升)。在观察到的临床特征中,无皮疹患者的病毒载量(CHIKV)对数平均值高于有皮疹的患者(6.61 vs 5.5,P = 0.0435)。
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引用次数: 0
HBsAg kinetics after 7 years of therapy with tenofovir disoproxil fumarate in a cohort of naïve patients affected by chronic hepatitis B with different genotypes 一组不同基因型的慢性乙型肝炎新患者接受富马酸替诺福韦二吡呋酯治疗 7 年后的 HBsAg 动力学研究
Pub Date : 2024-03-01 DOI: 10.1016/j.imj.2024.100087
Lucio Boglione , Tommaso Lupia , Giacomo Stroffolini , Valentina Dodaro , Giovanni Di Perri

The role of different genotypes in nucleos(t)ide analogs (NAs) treatment is still debated. Previous studies conducted on special populations evidenced that the E genotype had the lower virological and serological response. This descriptive study aims to recognize the hepatitis B “s” antigen (HBsAg) decline during tenofovir disoproxil fumarate (TDF) treatment in a cohort of patient affected by chronic hepatitis B (CHB). We retrospectively included all patients with CHB treated with TDF between April 2007 and March 2012 with a duration of treatment of 7 years. Kinetics of HBsAg was determined as serological response in this cohort. We include 110 subjects; virological response was observed in all subjects with genotypes A, B, and D; in 17 patients with C genotype (94.4%) and 24 with E genotype (96%). HBeAg loss was observed in 2 patients with genotype A (50%), 3 with B (100%), 0 with C (0%), 1 with D (20%), and 1 with E genotype (25%). In multivariate analysis we observed as predictive factors of HBsAg decline the baseline level of HBsAg (OR = 1.467; 95%CI: 1.221–5.113; p = 0.017) and viral genotypes (OR = 11.218; 95%CI: 5.441–41.138; p < 0.001). This study confirmed higher HBsAg decline after 7 years of treatment in A and B genotypes, and lower in C, E, and D genotypes. However, no evidence is enough to choose a single NAs, but in special populations, as well as in genotype E, the use of TDF should be preferred to entecavir.

不同基因型在核苷(t)类似物(NAs)治疗中的作用仍存在争议。以前对特殊人群进行的研究表明,E 基因型的病毒学和血清学反应较低。这项描述性研究旨在了解富马酸替诺福韦二吡呋酯(TDF)治疗期间慢性乙型肝炎(CHB)患者队列中乙肝 "s "抗原(HBsAg)下降的情况。我们回顾性地纳入了2007年4月至2012年3月期间接受TDF治疗的所有慢性乙型肝炎患者,治疗时间为7年。HBsAg 的动力学被确定为该队列中的血清学应答。我们共纳入了 110 名受试者;所有基因型为 A、B 和 D 的受试者都观察到了病毒学应答;基因型为 C 的患者有 17 人(94.4%),基因型为 E 的患者有 24 人(96%)。2 名基因型为 A 的患者(50%)、3 名基因型为 B 的患者(100%)、0 名基因型为 C 的患者(0%)、1 名基因型为 D 的患者(20%)和 1 名基因型为 E 的患者(25%)出现 HBeAg 消失。在多变量分析中,我们发现 HBsAg 基线水平(OR = 1.467; 95%CI: 1.221-5.113; p = 0.017)和病毒基因型(OR = 11.218; 95%CI: 5.441-41.138; p <0.001)是 HBsAg 下降的预测因素。这项研究证实,治疗 7 年后,A 和 B 基因型患者的 HBsAg 下降率较高,而 C、E 和 D 基因型患者的下降率较低。然而,没有足够的证据表明可以选择单一的 NAs,但在特殊人群和基因型 E 中,使用 TDF 应优于恩替卡韦。
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引用次数: 0
Primary nasopharyngeal carcinoma with cerebrospinal fluid EBV positivity: A case report and mini literature review 原发性鼻咽癌伴脑脊液 EBV 阳性:病例报告和小型文献综述
Pub Date : 2024-03-01 DOI: 10.1016/j.imj.2024.100089
Jinli Feng , Shuang Wang , Hongli Zhang, Jun Zhao, Xuling Wang

Background

To summarize the diagnosis and treatment of a patient with nasopharyngeal carcinoma and cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) positivity (determined by next-generation sequencing), review the relevant literature, and explore the significance of EBV presence in the CSF of patients with nasopharyngeal carcinoma.

Methods

A patient presenting with headache as the initial symptom was diagnosed with nasopharyngeal carcinoma and admitted to the Eighth Medical Center of Chinese PLA General Hospital on March 3, 2021. Available databases were screened for reports on nasopharyngeal carcinoma with EBV-positive CSF and analyzed. The patients’ general information, initial symptoms, treatment, and prognosis were subsequently evaluated.

Results

EBV-positive CSF is commonly observed in patients with recurrent nasopharyngeal carcinoma. However, no reports of EBV-positive CSF in patients with primary nasopharyngeal carcinoma have been published to date.

Conclusion

The presence of EBV in the CSF of patients with recurrent nasopharyngeal carcinoma is indicative of a poor prognosis. Thus, newly diagnosed nasopharyngeal carcinoma patients should undergo a lumbar puncture as soon as possible to have their CSF tested for EBV. Such a measure would promptly predict the prognosis and facilitate the development of a personalized treatment strategy.

背景概述一名鼻咽癌患者脑脊液(CSF)EB病毒(Epstein-Barr virus,EBV)阳性(通过新一代测序确定)的诊断和治疗,回顾相关文献,探讨鼻咽癌患者脑脊液中EBV存在的意义。方法2021年3月3日,中国人民解放军总医院第八医学中心收治了一名以头痛为首发症状的鼻咽癌患者。对现有数据库中关于鼻咽癌伴 EBV 阳性 CSF 的报告进行了筛选和分析。结果EBV阳性CSF常见于复发性鼻咽癌患者。结论复发性鼻咽癌患者 CSF 中出现 EBV 阳性表明预后不良。因此,新确诊的鼻咽癌患者应尽快进行腰椎穿刺,检测 CSF 中的 EBV。这样做可以及时预测预后,有助于制定个性化的治疗策略。
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引用次数: 0
Diagnosing and reintegrating traceability of infectious diseases via metagenomic next-generation sequencing: Study of a severe case of Rickettsia japonica infection 通过元基因组下一代测序诊断和重新整合传染病的可追溯性:日本立克次体感染重症病例研究
Pub Date : 2024-03-01 DOI: 10.1016/j.imj.2024.100094
Zhenhua Lu , Jing Han , Yuanyuan Wang , Zhen He , Shuxuan Song , Kun Liu , Zhongjun Shao

Background

In this study, we present a case of Japanese spotted fever (JSF) caused by Rickettsia japonica and use this case to investigate the process of diagnosing and reintegrating traceability of infectious diseases via metagenomic next-generation sequencing (mNGS).

Methods

From data relating to epidemiological history, clinical and laboratory examinations, and mNGS sequencing, a diagnosis of severe JSF was concluded.

Results

A detailed field epidemiological investigation discovered parasitic Haemaphysalis longicornis from a host animal (dog) in the domicile of the patient, within which R. japonica was detected, along with a diverse array of other potentially pathogenic microorganisms that could cause other infectious diseases.

Conclusion

The mNGS provided an efficient method to diagnose JSF infection. This methodology could also be applied to field epidemiological investigations to establish the traceability of infectious diseases.

背景在本研究中,我们介绍了一例由日本立克次体引起的日本斑疹热(JSF)病例,并利用该病例研究了通过元基因组下一代测序(mNGS)诊断和重新整合传染病可追溯性的过程。方法根据流行病学史、临床和实验室检查以及 mNGS 测序的相关数据,得出了严重日本斑疹热的诊断结论。结果通过详细的现场流行病学调查,从患者住所的宿主动物(狗)身上发现了寄生虫长角鲈,并在其中检测到了R. japonica,同时还发现了其他多种可能导致其他传染病的潜在病原微生物。这一方法也可用于实地流行病学调查,以建立传染病的可追溯性。
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引用次数: 0
Innovative applications of artificial intelligence during the COVID-19 pandemic COVID-19 大流行期间人工智能的创新应用
Pub Date : 2024-03-01 DOI: 10.1016/j.imj.2024.100095
Chenrui Lv , Wenqiang Guo , Xinyi Yin , Liu Liu , Xinlei Huang , Shimin Li , Li Zhang

The COVID-19 pandemic has created unprecedented challenges worldwide. Artificial intelligence (AI) technologies hold tremendous potential for tackling key aspects of pandemic management and response. In the present review, we discuss the tremendous possibilities of AI technology in addressing the global challenges posed by the COVID-19 pandemic. First, we outline the multiple impacts of the current pandemic on public health, the economy, and society. Next, we focus on the innovative applications of advanced AI technologies in key areas such as COVID-19 prediction, detection, control, and drug discovery for treatment. Specifically, AI-based predictive analytics models can use clinical, epidemiological, and omics data to forecast disease spread and patient outcomes. Additionally, deep neural networks enable rapid diagnosis through medical imaging. Intelligent systems can support risk assessment, decision-making, and social sensing, thereby improving epidemic control and public health policies. Furthermore, high-throughput virtual screening enables AI to accelerate the identification of therapeutic drug candidates and opportunities for drug repurposing. Finally, we discuss future research directions for AI technology in combating COVID-19, emphasizing the importance of interdisciplinary collaboration. Though promising, barriers related to model generalization, data quality, infrastructure readiness, and ethical risks must be addressed to fully translate these innovations into real-world impacts. Multidisciplinary collaboration engaging diverse expertise and stakeholders is imperative for developing robust, responsible, and human-centered AI solutions against COVID-19 and future public health emergencies.

COVID-19 大流行给全世界带来了前所未有的挑战。人工智能(AI)技术在应对大流行病管理和响应的关键方面具有巨大潜力。在本综述中,我们将讨论人工智能技术在应对 COVID-19 大流行带来的全球挑战方面的巨大潜力。首先,我们概述了当前流行病对公共卫生、经济和社会的多重影响。接下来,我们重点介绍先进人工智能技术在 COVID-19 预测、检测、控制和治疗药物发现等关键领域的创新应用。具体来说,基于人工智能的预测分析模型可以利用临床、流行病学和 Omics 数据来预测疾病的传播和患者的预后。此外,深度神经网络还能通过医学成像进行快速诊断。智能系统可以支持风险评估、决策和社会感应,从而改善流行病控制和公共卫生政策。此外,高通量虚拟筛选使人工智能能够加快候选治疗药物的确定,并为药物再利用提供机会。最后,我们讨论了人工智能技术在抗击 COVID-19 方面的未来研究方向,强调了跨学科合作的重要性。尽管前景广阔,但要将这些创新充分转化为现实世界的影响,必须解决与模型泛化、数据质量、基础设施准备情况和道德风险有关的障碍。要开发稳健、负责任、以人为本的人工智能解决方案来应对 COVID-19 和未来的公共卫生突发事件,就必须开展多学科合作,让不同的专业知识和利益相关者参与进来。
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引用次数: 0
Rapid adaptive substitution of L226Q in HA protein increases the pathogenicity of H9N2 viruses in mice HA 蛋白中 L226Q 的快速适应性替代增加了 H9N2 病毒对小鼠的致病性
Pub Date : 2024-02-01 DOI: 10.1016/j.imj.2024.100090
Min Tan, Ye Zhang, H. Bo, Xi-yan Li, Shu-mei Zou, Lei Yang, Jia Liu, Qi Chen, Xiaohao Xu, Wenfei Zhu, Dayan Wang
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引用次数: 0
Primary nasopharyngeal carcinoma with cerebrospinal fluid EBV positivity: a case report and mini literature review 原发性鼻咽癌伴脑脊液 EBV 阳性:病例报告和小型文献综述
Pub Date : 2024-02-01 DOI: 10.1016/j.imj.2024.100089
Jinli Feng, Shuang Wang, Hongli Zhang, Jun Zhao, Xuling Wang
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引用次数: 0
Viremia and clinical manifestations in acute febrile patients of Chikungunya infection during the 2016 CHIKV outbreak in Delhi, India 2016年印度德里CHIKV疫情期间基孔肯雅病毒感染急性发热患者的病毒血症和临床表现
Pub Date : 2024-02-01 DOI: 10.1016/j.imj.2024.100088
R. Sagar, Siva Raghavendhar, Vineet Jain, Naushad Khan, A. Chandele, Ashok Kumar Patel, M. Kaja, Pratima Ray, Neera Kapoor
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引用次数: 0
A major pain in the hip - Destruction of the left acetabulum and femoral head secondary to Tuberculosis: A case report and review of the literature 髋部剧痛继发于肺结核的左侧髋臼和股骨头破坏--病例报告和文献综述
Pub Date : 2023-12-16 DOI: 10.1016/j.imj.2023.12.001
Dominic A. Haigh , Dillan Mistry , Hamzah Z. Farooq , Katherine M.B. Ajdukiewicz

A 68-year-old-gentleman presented with left hip pain, night sweats, fatigue, and weight loss. He had previously experienced pain with white discharge until he underwent an arthroscopic washout and reduction. The left lower limb was shortened and wasted with limited hip movements. He had recently travelled to Zambia, his country of origin. Imaging demonstrated a large mass with chronic erosions of the acetabulum and femoral head. Synovial biopsy grew Mycobacterium tuberculosis, which was treated with rifampicin, isoniazid, pyrazinamide, and ethambutol for 2 months then 4 months of rifampicin and isoniazid. Whole genome sequencing indicated full sensitivity. Complex reconstructive surgery is scheduled, with a custom femoral head and acetabulum. This case illustrates the importance of considering tuberculosis in patients with erosive joint pathology and a multidisciplinary approach as delayed diagnosis results in high morbidity. Prompt diagnosis using newer modalities such as whole genome sequencing on synovial fluid can enable timely treatment.

一位 68 岁的男士因左髋部疼痛、盗汗、乏力和体重减轻前来就诊。在接受关节镜冲洗和缩小术之前,他一直感到疼痛并伴有白色分泌物。他的左下肢缩短、萎缩,髋关节活动受限。他最近曾前往原籍国赞比亚。影像学检查显示,他的髋臼和股骨头有一个慢性侵蚀的巨大肿块。滑膜活检发现了结核分枝杆菌,患者接受了为期两个月的利福平、异烟肼、吡嗪酰胺和乙胺丁醇治疗,随后又接受了为期四个月的利福平和异烟肼治疗。全基因组测序结果表明患者具有完全的敏感性。计划进行复杂的重建手术,定制股骨头和髋臼。这个病例说明,在关节侵蚀性病变患者中考虑结核病并采用多学科方法非常重要,因为延迟诊断会导致高发病率。采用滑液全基因组测序等新方法进行及时诊断,可以使患者得到及时治疗。
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引用次数: 0
期刊
Infectious Medicine
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