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CRISPR-Cas9 System: A Revolutionary Tool in the Fight Against Antimicrobial Resistance: Retracted CRISPR-Cas9系统:对抗耐药性的革命性工具:撤回
Q3 INFECTIOUS DISEASES Pub Date : 2021-01-19 DOI: 10.1097/IM9.0000000000000049
Osmond C Ekwebelem, Job C. Aleke, Ekenedirichukwu S. Ofielu, Obinna V. Nnorom-Dike
Abstract The rapidly evolving world of antimicrobial resistance has not only made it difficult to combat infectious diseases, but during the last decades also brought the discovery of novel antimicrobials to a standstill. In recent years, researchers discovered the potential of the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (CRISPR-Cas) system as an alternative therapeutic. Since the unearthing of CRISPR-Cas9 as an “adaptive immune system” of bacteria, the CRISPR-Cas9 system has been improved into a state-of-the-art genetic engineering tool, with an impressive ability to cause specific gene insertions and/or gene deletions, in almost all microorganisms. The emerging picture suggests that the CRISPR-Cas9 system can be exploited in a sequence-specific manner to selectively eliminate individual bacterial strains in a mixed microbial population, and/or re-sensitize bacteria to antibiotics. These findings have not only revolutionized biomedical research, but might also prove to be pivotal in creating novel alternative treatments for multidrug-resistant infections. Here, we discussed the up-to-date findings reported in this area, as well as the approaches involved in the utilization of CRISPR-Cas9 as a novel technology in the fight against antimicrobial resistance. We also highlighted recent studies that have exploited the CRISPR-Cas9 system in the context of targeting pathogenic and drug-resistant bacteria.
快速发展的抗菌素耐药性世界不仅使对抗传染病变得困难,而且在过去的几十年里,也使新型抗菌素的发现陷入停滞。近年来,研究人员发现了聚集规律间隔短回文重复序列(CRISPR)相关(CRISPR- cas)系统作为替代治疗的潜力。自从CRISPR-Cas9作为细菌的“适应性免疫系统”被发现以来,CRISPR-Cas9系统已被改进为最先进的基因工程工具,具有在几乎所有微生物中引起特定基因插入和/或基因缺失的令人印象深刻的能力。新出现的图像表明,CRISPR-Cas9系统可以以序列特异性的方式被利用,以选择性地消除混合微生物群体中的单个细菌菌株,和/或使细菌对抗生素重新敏感。这些发现不仅使生物医学研究发生了革命性的变化,而且可能在为耐多药感染创造新的替代疗法方面发挥关键作用。在这里,我们讨论了这一领域的最新发现,以及利用CRISPR-Cas9作为对抗抗菌素耐药性的新技术所涉及的方法。我们还强调了最近在靶向致病性和耐药细菌的背景下利用CRISPR-Cas9系统的研究。
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引用次数: 5
A Retrospective Study of the Epidemiologic and Clinical Characteristics of COVID-19 Among Hospitalized Patients in Quanzhou, China. 泉州市住院患者新冠肺炎流行病学及临床特征的回顾性研究
Q3 INFECTIOUS DISEASES Pub Date : 2021-01-15 eCollection Date: 2021-03-01 DOI: 10.1097/IM9.0000000000000048
Wenhuang Chen, Yijian Lin, Hongbo Huang, Maosheng Cai, Dongheng Lin, Milong Su, Zhijun Su, Xibin Zhuang, Xueping Yu

Coronavirus disease 2019 (COVID-19) has spread throughout China. However, information about COVID-19 in cities and regions outside Wuhan is limited and the indicators that predict the length of hospital stay for patients with COVID-19 are unclear. Therefore, we collected clinical data from 47 patients with COVID-19 in Quanzhou City. The median age was 38 years [interquartile range (IQR): 31-50 years], and 24 (51%) were male. There were 8 mild, 36 moderate, and 3 severe/critical cases. The median interval from exposure to disease onset was 13 days (IQR: 8-18 days). The incidence of severe/critical cases was 33% (3/10) in patients with hypertension. Common symptoms included fever (83%), cough (77%), fatigue (40%), a sore, dry throat (28%), and diarrhea (21%). One patient (2%) developed respiratory distress syndrome on day 13 of inpatient treatment. Six patients had leukopenia, 17 had elevated C-reactive protein (CRP), and 8 had lymphocytopenia and elevated lactate dehydrogenase (LDH). The median length of hospitalization was 22 days (IQR: 16-30 days). Dynamic monitoring of LDH, CRP, and neutrophil-lymphocyte ratio predicted whether length of hospitalization would exceed 21 days. Most patients presented with mild and moderate disease. Patients with hypertension were more likely to become severe or critical. Dynamic monitoring of LDH, CRP, and neutrophil-lymphocyte ratio levels can help predict delayed discharge from the hospital.

摘要2019冠状病毒病(新冠肺炎)已在中国蔓延。然而,武汉以外城市和地区有关新冠肺炎的信息有限,预测新冠肺炎患者住院时间的指标也不清楚。因此,我们收集了泉州市47例新冠肺炎患者的临床数据。中位年龄为38岁 年龄[四分位间距(IQR):31-50岁],24岁(51%)为男性。轻度8例,中度36例 严重/危重病例。从接触到发病的中位间隔为13 天(IQR:8-18 天)。高血压患者的重症/危重病例发生率为33%(3/10)。常见症状包括发烧(83%)、咳嗽(77%)、疲劳(40%)、喉咙痛、干燥(28%)和腹泻(21%)。一名患者(2%)在住院治疗的第13天出现呼吸窘迫综合征。6名患者白细胞减少,17名患者C反应蛋白(CRP)升高,8名患者淋巴细胞减少和乳酸脱氢酶(LDH)升高。住院时间中位数为22 天(IQR:16-30 天)。LDH、CRP和中性粒细胞淋巴细胞比率的动态监测预测住院时间是否会超过21 天。大多数患者表现为轻度和中度疾病。高血压患者更有可能变得严重或危重。LDH、CRP和中性粒细胞淋巴细胞比率水平的动态监测有助于预测延迟出院。
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引用次数: 0
Dietary Pterostilbene Inhibited Colonic Inflammation in Dextran-Sodium-Sulfate-Treated Mice: A Perspective of Gut Microbiota 膳食紫檀芪抑制右旋糖酐-硫酸钠处理小鼠的结肠炎症:肠道微生物群的观点
Q3 INFECTIOUS DISEASES Pub Date : 2021-01-08 DOI: 10.1097/IM9.0000000000000047
Fang Li, Qi Wang, Yanhui Han, Mingyue Song, Xiaokun Cai, Timothy R. Goulette, Hang Xiao
Abstract Dietary interventions based on the use of bioactive nutraceuticals might offer an effective adjuvant therapeutic and preventive method for inflammatory bowel disease by reshaping colitis-associated bacterial dysbiosis. The current study aimed to determine the anti-inflammatory effect of pterostilbene (PTE, a methylated derivative of resveratrol) and its potential modulatory roles in gut microbiota in a dextran sodium sulfate (DSS)-induced colitis mouse model. Our results supported our hypothesis that dietary PTE exerted protective effects against colonic inflammation; evidenced by the reduced colonic tissue damage, decreased disease activity index, and lowered production of pro-inflammatory cytokines such as interferon gamma, interleukin (IL)-2, IL-4, and IL-6 in the colon of DSS-treated mice. Moreover, α-diversity analysis indicated that dietary PTE significantly improved gut microbial evenness and diversity. Noteworthy, PTE modified gut microbiota composition toward a healthier profile by boosting the richness of Bifidobacterium and decreasing the distribution of pathogenic Bilophila and Rc4-4. Pearson correlation analysis also revealed strong associations between the shifting of gut microbiota and expression of inflammatory cytokines in the colon. Overall, our study demonstrated that dietary PTE alleviated the severity of colitis in DSS-treated mice and gut microbiota may play an indispensable role in this process mechanistically.
摘要基于生物活性营养品的饮食干预可能通过重塑结肠炎相关细菌微生态失调,为炎症性肠病提供一种有效的辅助治疗和预防方法。本研究旨在确定在右旋糖酐-硫酸钠(DSS)诱导的结肠炎小鼠模型中,紫檀烯(PTE,白藜芦醇的甲基化衍生物)的抗炎作用及其在肠道微生物群中的潜在调节作用。我们的研究结果支持了我们的假设,即膳食PTE对结肠炎症具有保护作用;DSS处理的小鼠结肠中结肠组织损伤减少、疾病活性指数降低以及促炎细胞因子如干扰素γ、白细胞介素(IL)-2、IL-4和IL-6的产生降低证明了这一点。此外,α-多样性分析表明,日粮PTE显著改善了肠道微生物的均匀性和多样性。值得注意的是,PTE通过提高双歧杆菌的丰富度和减少致病性嗜胆菌和Rc4-4的分布,使肠道微生物群组成更健康。Pearson相关性分析还揭示了肠道微生物群的转移与结肠中炎性细胞因子的表达之间的强烈关联。总之,我们的研究表明,在DSS治疗的小鼠中,膳食PTE减轻了结肠炎的严重程度,肠道微生物群可能在这一过程中发挥着不可或缺的作用。
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引用次数: 1
Probiotics and Their Metabolites Ameliorate Inflammatory Bowel Disease: A Critical Review 益生菌及其代谢产物改善炎症性肠病的研究进展
Q3 INFECTIOUS DISEASES Pub Date : 2020-12-30 DOI: 10.1097/IM9.0000000000000046
Y. Liang, Manman Liu, J. Pu, Zichun Zhu, Zining Gao, Qingqing Zhou, Q. Gu, Ping Li
Abstract Crohn disease and ulcerative colitis are the two main manifestations of inflammatory bowel disease (IBD), and both are highly morbid. However, the precise etiology of IBD is still unknown and effective therapeutics are yet to be discovered. It is becoming increasingly clear that a combination of factors, including genetic background, host immune response, and microbial reduced diversity status are related to IBD. The cardinal symptom of IBD patients is the imbalance of the intestinal microflora. According to previous studies, both probiotics and symbiotic microbiota can play a protective role through intestinal micro-ecosystem regulation, epithelial barrier integrity enhancement, and inflammation reduction. Therefore, probiotics can provide an alternative or auxiliary method to traditional IBD treatment. Here, we reviewed the possible pathogenesis of IBD, summarized the possible mechanisms of probiotics modulation of IBD, and emphasized the prevention and treatment targets of probiotics-mediated IBD, with the aim to provide theoretical support for the treatment of IBD patients by probiotics in clinical trials.
摘要克罗恩病和溃疡性结肠炎是炎症性肠病(IBD)的两种主要表现,两者都是高度病态的。然而,IBD的确切病因仍然未知,有效的治疗方法尚待发现。越来越清楚的是,遗传背景、宿主免疫反应和微生物多样性减少状态等多种因素与IBD有关。IBD患者的主要症状是肠道菌群失衡。根据先前的研究,益生菌和共生微生物群都可以通过调节肠道微生态系统、增强上皮屏障完整性和减少炎症发挥保护作用。因此,益生菌可以为传统IBD治疗提供一种替代或辅助方法。在此,我们回顾了IBD可能的发病机制,总结了益生菌调节IBD的可能机制,并强调了益生菌介导的IBD的预防和治疗靶点,旨在为临床试验中益生菌治疗IBD患者提供理论支持。
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引用次数: 15
The Impact of SARS-CoV-2 on the Human Immune System and Microbiome. 严重急性呼吸系统综合征冠状病毒2型对人体免疫系统和微生物组的影响
Q3 INFECTIOUS DISEASES Pub Date : 2020-12-23 eCollection Date: 2021-03-01 DOI: 10.1097/IM9.0000000000000045
Chuxi Wang, Xin Zhou, Meng Wang, Xin Chen

A recent outbreak of coronavirus disease 2019 (COVID-19) caused by the single-stranded enveloped RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global pandemic, after it was first reported in Wuhan in December 2019. SARS-CoV-2 is an emerging virus, and little is known about the basic characteristics of this pathogen, the underlying mechanism of infection, and the potential treatments. The immune system has been known to be actively involved in viral infections. To facilitate the development of COVID-19 treatments, the understanding of immune regulation by this viral infection is urgently needed. This review describes the mechanisms of immune system involvement in viral infections and provides an overview of the dysregulation of immune responses in COVID-19 patients in recent studies. Furthermore, we emphasize the role of gut microbiota in regulating immunity and summarized the impact of SARS-CoV-2 infection on the composition of the microbiome. Overall, this review provides insights for understanding and developing preventive and therapeutic strategies by regulating the immune system and microbiota.

摘要2019年12月首次在武汉报告后,由单链包膜RNA病毒严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的2019冠状病毒病(新冠肺炎)最近爆发,已发展为全球大流行。严重急性呼吸系统综合征冠状病毒2型是一种新出现的病毒,对这种病原体的基本特征、感染的潜在机制和潜在的治疗方法知之甚少。众所周知,免疫系统与病毒感染密切相关。为了促进新冠肺炎治疗的发展,迫切需要了解这种病毒感染的免疫调节。这篇综述描述了免疫系统参与病毒感染的机制,并概述了最近研究中新冠肺炎患者免疫反应的失调。此外,我们强调了肠道微生物群在调节免疫中的作用,并总结了严重急性呼吸系统综合征冠状病毒2型感染对微生物组组成的影响。总的来说,这篇综述通过调节免疫系统和微生物群,为理解和制定预防和治疗策略提供了见解。
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引用次数: 0
Microbiota, Viral Infection, and the Relationship to Human Diseases: An Area of Increasing Interest in the SARS-CoV-2 Pandemic. 微生物群、病毒感染及其与人类疾病的关系:严重急性呼吸系统综合征冠状病毒2型大流行日益引起关注的领域
Q3 INFECTIOUS DISEASES Pub Date : 2020-11-04 eCollection Date: 2021-03-01 DOI: 10.1097/IM9.0000000000000043
Matthew D Moore, Cassandra Suther, Yanjiao Zhou
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引用次数: 0
The Correlation Between Heart Failure and Gut Microbiome Metabolites. 心力衰竭与肠道微生物代谢物的相关性
IF 2 Q3 INFECTIOUS DISEASES Pub Date : 2020-11-04 eCollection Date: 2020-12-01 DOI: 10.1097/IM9.0000000000000042
Lina Chen, Senhao Li, Lanmu Ai, Jun Zhou, Junlin Huang, Feng Xu, Xiangyuan Zeng, Jia Han, Fangxue Yin, Yixin Zhu, Yifang Xie

Heart failure (HF) is a global public health problem, with morbidity and mortality increasing year by year. The gut microbiome actively affects the physiological and pathological activities of the human body in a variety of ways. More and more studies have suggested a strong correlation between HF and gut microbiome metabolites. Our review summarizes the specific alteration of these metabolites and their connection to the progression of HF, aiming at considering new approaches toward regulating the gut microbiome and using its metabolic pathways to treat HF, potentially decreasing the morbidity and mortality of HF as well as improving prognosis.

摘要心力衰竭是一个全球性的公共卫生问题,发病率和死亡率逐年上升。肠道微生物组以多种方式积极影响人体的生理和病理活动。越来越多的研究表明HF与肠道微生物组代谢产物之间存在着强烈的相关性。我们的综述总结了这些代谢产物的具体变化及其与HF进展的联系,旨在考虑调节肠道微生物组并利用其代谢途径治疗HF的新方法,从而潜在地降低HF的发病率和死亡率,并改善预后。
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引用次数: 0
Will Technology Rather Than Vaccination Be the Way to Control Pandemics? 控制流行病的方法是技术而不是疫苗吗?
Q3 INFECTIOUS DISEASES Pub Date : 2020-10-23 eCollection Date: 2020-12-01 DOI: 10.1097/IM9.0000000000000041
Sebastian Leptihn, Susan C Welburn
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引用次数: 0
Genetic Characterization of Streptococcus pyogenes emm89 Strains Isolated in Japan From 2011 to 2019. 2011 年至 2019 年在日本分离到的化脓性链球菌 emm89 菌株的遗传特征。
Q3 INFECTIOUS DISEASES Pub Date : 2020-10-21 eCollection Date: 2020-12-01 DOI: 10.1097/IM9.0000000000000038
Yujiro Hirose, Masaya Yamaguchi, Norihiko Takemoto, Tohru Miyoshi-Akiyama, Tomoko Sumitomo, Masanobu Nakata, Tadayoshi Ikebe, Tomoki Hanada, Takahiro Yamaguchi, Ryuji Kawahara, Rumi Okuno, Hitoshi Otsuka, Yuko Matsumoto, Yuji Terashima, Yu Kazawa, Noriko Nakanishi, Kaoru Uchida, Yumi Akiyama, Kaori Iwabuchi, Chikara Nakagawa, Kazunari Yamamoto, Victor Nizet, Shigetada Kawabata

Invasive infection caused by Streptococcus pyogenes emm89 strains has been increasing in several countries linked to a recently emergent clade of emm89 strains, designated clade 3. In Japan, the features of emm89 S. pyogenes strains, such as clade classification, remains unknown. In this study, we collected emm89 strains isolated from both streptococcal toxic shock syndrome (STSS) (89 STSS isolates) and noninvasive infections (72 non-STSS isolates) in Japan from 2011 to 2019, and conducted whole-genome sequencing and comparative analysis, which resulted in classification of a large majority into clade 3 regardless of disease severity. In addition, invasive disease-associated factors were found among emm89 strains, including mutations of control of virulence sensor, and absence of the hylP1 gene encoding hyaluronidase. These findings provide new insights into genetic features of emm89 strains.

化脓性链球菌emm89菌株引起的侵入性感染在一些国家呈上升趋势,这与最近出现的emm89菌株支系(即支系3)有关。在日本,emm89 化脓性链球菌菌株的特征(如支系分类)仍然未知。在本研究中,我们收集了 2011 年至 2019 年期间在日本从链球菌中毒性休克综合征(STSS)(89 株 STSS 分离株)和非侵袭性感染(72 株非 STSS 分离株)中分离出的 emm89 菌株,并进行了全基因组测序和比较分析,结果发现无论疾病严重程度如何,绝大多数菌株都被归入支系 3。此外,在emm89菌株中还发现了侵袭性疾病相关因素,包括毒力传感器控制突变和编码透明质酸酶的hylP1基因缺失。这些发现为了解emm89菌株的遗传特征提供了新的视角。
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引用次数: 0
Characteristics of Liver Functions in Patients With COVID-19 and Construction of a Prognostic Evaluation Decision Model Based on Liver Functions. 新冠肺炎患者肝功能特点及基于肝功能的预后评估决策模型的构建
Q3 INFECTIOUS DISEASES Pub Date : 2020-10-20 eCollection Date: 2020-12-01 DOI: 10.1097/IM9.0000000000000039
Tongtong Pan, Dazhi Chen, Chenwei Pan, Yi Kang, Junping Liu, Feifei Su, Liang Hong, Huili Li, Hui Zhao, Zhuo Lin, Xiaodong Wang, Hongwei Lin, Qianjing Du, Chao Cai, Yongping Chen

A number of studies have suggested that coronavirus disease 2019 (COVID-19) can cause liver damage. However, clinical features and outcome of COVID-19 in patients with liver injury remain to be further investigated. In this study, the clinical data of 265 COVID-19 patients admitted to seven tertiary hospitals were collected. Based on a threshold for transaminase or total bilirubin levels at two times the normal upper limit, patients were divided into mild or moderate/severe liver injury groups. Among the 265 patients, 183 patients showed liver injury within 48 hours of admission. Aspartate aminotransferase levels were predominantly elevated in the liver injury group, but albumin levels were reduced. Moreover, fibrinogen and D-dimer were significantly increased. Furthermore, 68% of the patients with moderate/severe liver injury had one or more underlying diseases. Almost half of these patients developed acute respiratory distress syndrome (44%) and secondary infections (46%). These patients showed increased interleukin-6 and interleukin-10 levels and a decrease in PaO2 and the oxygenation index. In addition, levels of alanine aminotransferase, aspartate aminotransferase, and albumin were correlated with the oxygenation index, D-dimer and lymphocyte counts. Furthermore, a novel prognostic assessment model based on liver function was established, which accuracy reached 88% and was able to accurately assess the prognosis of COVID-19 patients.

多项研究表明,冠状病毒病2019 (COVID-19)可导致肝脏损伤。然而,COVID-19在肝损伤患者中的临床特征和预后仍有待进一步研究。本研究收集了7家三级医院收治的265例新冠肺炎患者的临床资料。根据转氨酶或总胆红素水平阈值为正常上限的两倍,将患者分为轻度或中度/重度肝损伤组。265例患者中,有183例患者在入院48小时内出现肝损伤。肝损伤组天冬氨酸转氨酶水平明显升高,而白蛋白水平降低。纤维蛋白原和d -二聚体显著升高。此外,68%的中度/重度肝损伤患者有一种或多种基础疾病。这些患者中几乎有一半出现急性呼吸窘迫综合征(44%)和继发性感染(46%)。这些患者表现出白细胞介素-6和白细胞介素-10水平升高,PaO2和氧合指数下降。此外,丙氨酸转氨酶、天冬氨酸转氨酶和白蛋白水平与氧合指数、d -二聚体和淋巴细胞计数相关。建立了基于肝功能的新型预后评估模型,准确率达到88%,能够准确评估COVID-19患者的预后。
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引用次数: 0
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Infectious microbes & diseases
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