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Expanded Scope of Bacillus Calmette-Guerin (BCG) Vaccine Applicability in Disease Prophylaxis, Diagnostics, and Immunotherapeutics. 卡介苗(BCG)疫苗在疾病预防、诊断和免疫治疗中的适用范围扩大
Q3 INFECTIOUS DISEASES Pub Date : 2020-10-20 eCollection Date: 2020-12-01 DOI: 10.1097/IM9.0000000000000040
Oluwafolajimi A Adesanya, Christabel I Uche-Orji, Yeshua A Adedeji, John I Joshua, Adeniyi A Adesola, Chibuike J Chukwudike

Following the discovery of the Bacillus Calmette-Guerin (BCG) vaccine, its efficacy against Mycobacterium tuberculosis was soon established, with several countries adopting universal BCG vaccination schemes for their populations. Soon, however, studies aimed to further establish the efficacy of the vaccine in different populations discovered that the vaccine has a larger effect in reducing mortality rate than could be explained by its effect on tuberculosis alone, which sparked suggestions that the BCG vaccine could have effects on other unrelated or non-mycobacterial pathogens causing diseases in humans. These effects were termed heterologous, non-specific or off-target effects and have been shown to be due to both innate and adaptive immune system responses. Experiments carried out in a bid to further understand these effects led to many more discoveries about the applicability of the BCG vaccine for the prevention, diagnosis, and treatment of certain disease conditions. As we approach the second century since the discovery of the vaccine, we believe it is timely to review these interesting applications of the BCG vaccine, such as in the prevention of diabetes, atherosclerosis, and leukemia; the diagnosis of Kawasaki disease; and the treatment of multiple sclerosis, non-muscle invading bladder cancer, and stage III melanoma. Furthermore, complications associated with the administration of the BCG vaccine to certain groups of patients, including those with severe combined immunodeficiency and HIV, have been well described in literature, and we conclude by describing the mechanisms behind these complications and discuss their implications on vaccination strategies, especially in low-resource settings.

随着卡介苗(Bacillus calmetter - guerin, BCG)疫苗的发现,其抗结核分枝杆菌的有效性很快得到了证实,一些国家在其人口中普遍采用了卡介苗接种方案。然而,不久,旨在进一步确定疫苗在不同人群中的功效的研究发现,该疫苗在降低死亡率方面的作用比仅对结核病的作用更大,这引发了人们的建议,即卡介苗可能对引起人类疾病的其他不相关或非分枝杆菌病原体也有影响。这些效应被称为异源、非特异性或脱靶效应,并已被证明是由于先天和适应性免疫系统反应。为了进一步了解这些影响而进行的实验导致了更多关于卡介苗在预防、诊断和治疗某些疾病条件方面适用性的发现。在我们接近卡介苗发现的第二个世纪之际,我们认为是时候回顾一下卡介苗在预防糖尿病、动脉粥样硬化和白血病等方面的有趣应用;川崎病的诊断;以及多发性硬化症、非肌肉侵袭性膀胱癌和III期黑色素瘤的治疗。此外,与某些患者群体(包括严重联合免疫缺陷和HIV患者)接种卡介苗相关的并发症已经在文献中得到了很好的描述,我们通过描述这些并发症背后的机制并讨论它们对疫苗接种策略的影响,特别是在资源匮乏的环境中。
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引用次数: 0
On or Off: Life-Changing Decisions Made by Vibrio cholerae Under Stress. 开或关:霍乱弧菌在压力下做出的改变生命的决定。
Q3 INFECTIOUS DISEASES Pub Date : 2020-10-14 eCollection Date: 2020-12-01 DOI: 10.1097/IM9.0000000000000037
Yitian Zhou, Zachariah L Lee, Jun Zhu

Vibrio cholerae, the causative agent of the infectious disease, cholera, is commonly found in brackish waters and infects human hosts via the fecal-oral route. V. cholerae is a master of stress resistance as V. cholerae's dynamic lifestyle across different physical environments constantly exposes it to diverse stressful circumstances. Specifically, V. cholerae has dedicated genetic regulatory networks to sense different environmental cues and respond to these signals. With frequent outbreaks costing a tremendous amount of lives and increased global water temperatures providing more suitable aquatic habitats for V. cholerae, cholera pandemics remain a probable catastrophic threat to humanity. Understanding how V. cholerae copes with different environmental stresses broadens our repertoire of measures against infectious diseases and expands our general knowledge of prokaryotic stress responses. In this review, we summarize the regulatory mechanisms of how V. cholerae fights against stresses in vivo and in vitro.

霍乱弧菌是传染病霍乱的病原体,通常存在于咸水中,通过粪口途径感染人类宿主。霍乱弧菌是抗应激高手,因为霍乱弧菌在不同物理环境中的动态生活方式使其不断面临各种应激环境。具体来说,霍乱弧菌有专门的基因调控网络来感知不同的环境线索并对这些信号做出反应。霍乱的频繁爆发夺走了大量生命,而全球水温的升高又为霍乱弧菌提供了更合适的水生栖息地,因此霍乱大流行仍可能对人类造成灾难性威胁。了解霍乱弧菌如何应对不同的环境压力拓宽了我们应对传染病的措施范围,并扩展了我们对原核生物压力反应的一般知识。在这篇综述中,我们总结了霍乱弧菌如何在体内和体外对抗压力的调控机制。
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引用次数: 0
Sex Bias in Sample Collections From Bats, the Culprit of SARS Coronavirus, SARS-Coronavirus-2, and Other Emerging Viruses. 蝙蝠——SARS冠状病毒、SARS冠状病毒-2和其他新出现的病毒的罪魁祸首——样本采集中的性别偏见
Q3 INFECTIOUS DISEASES Pub Date : 2020-10-06 eCollection Date: 2020-12-01 DOI: 10.1097/IM9.0000000000000036
Susanna K P Lau, Zirong He, Ken P K Lin, Patrick C Y Woo
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引用次数: 0
Microbiological Characteristics and Antibiotic Sensitivity in Patients with Nosocomial Spontaneous Bacterial Peritonitis Caused by Escherichia coli: A Multicenter Study. 大肠杆菌引起的院内自发性细菌性腹膜炎的微生物学特征和抗生素敏感性:一项多中心研究
Q3 INFECTIOUS DISEASES Pub Date : 2020-08-07 eCollection Date: 2020-12-01 DOI: 10.1097/IM9.0000000000000035
Bo Tu, Yuening Zhang, Jingfeng Bi, Zhe Xu, Lei Shi, Xin Zhang, Peng Zhao, Dawei Zhang, Guang Yang, Enqiang Qin

Escherichia coli is a prevalent causative pathogen of spontaneous bacterial peritonitis (SBP). In this retrospective study, we investigated the microbiological characteristics and antibiotic susceptibility of E. coli clinical isolates obtained from liver cirrhosis patients suffering from nosocomial SBP. Our results showed that extended-spectrum β-lactamase (ESBL)-producing E. coli accounted for 47% of the cases, while 62% of the isolates were multi-drug resistant (MDR) pathogens. ESBL-producing and MDR isolates showed high incidences of resistance to third-generation cephalosporins, but they displayed susceptibility to carbapenems, β-lactamase inhibitors, and aminoglycosides. Importantly, liver cirrhosis patients with MDR E. coli SBP showed a significantly higher death rate than patients with non-MDR infections (P = 0.021). The 30-day mortality of nosocomial SBP was independently correlated with female gender [odds ratio (OR) = 5.200, 95% confidence interval (CI) = 1.194-22.642], liver failure (OR = 9.609, 95% CI = 1.914-48.225), hepatocellular carcinoma (OR = 8.176, 95% CI = 2.065-32.364), hepatic encephalopathy (OR = 8.176, 95% CI = 2.065-32.364), model of end-stage liver disease score (OR = 1.191, 95% CI = 1.053-1.346), white blood cell count (OR = 0.847, 95% CI = 0.737-0.973), and ascites polymorphonuclear (OR = 95.903, 95% CI = 3.410-2697.356). In conclusion, third-generation cephalosporins may be inappropriate for empiric treatment of nosocomial SBP caused by E. coli, due to the widespread presence of ESBLs and high incidence of MDR pathogens.

摘要大肠杆菌是自发性细菌性腹膜炎(SBP)的常见致病菌。在这项回顾性研究中,我们研究了从肝硬化院内性收缩压患者中获得的大肠杆菌临床分离株的微生物学特征和抗生素敏感性。结果显示,产广谱β-内酰胺酶(ESBL)的大肠杆菌占47%,而62%的分离株为耐多药(MDR)病原体。产esbl和MDR分离株对第三代头孢菌素耐药发生率高,但对碳青霉烯类、β-内酰胺酶抑制剂和氨基糖苷类敏感。重要的是,MDR型大肠杆菌SBP肝硬化患者的死亡率明显高于非MDR型感染患者(P = 0.021)。院内SBP的30天死亡率是独立与女性性别(比值比(或)= 5.200,95%可信区间(CI) = 1.194 - -22.642),肝功能衰竭(或= 9.609,95% CI -48.225 = 1.914),肝细胞癌(或= 8.176,95% CI -32.364 = 2.065),肝性脑病(或= 8.176,95% CI -32.364 = 2.065),终末期肝病评分模型(或= 1.191,95% CI -1.346 = 1.053),白细胞计数(或= 0.847,95% CI = 0.737 - -0.973),腹水多形核(OR = 95.903, 95% CI = 3.410 ~ 2697.356)。综上所述,由于ESBLs的广泛存在和耐多药病原菌的高发,第三代头孢菌素可能不适合经验性治疗大肠杆菌引起的医院性收缩压。
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引用次数: 0
Will the Overuse of Antibiotics During the Coronavirus Pandemic Accelerate Antimicrobial Resistance of Bacteria? 冠状病毒大流行期间抗生素的过度使用会加速细菌的抗菌素耐药性吗?
Q3 INFECTIOUS DISEASES Pub Date : 2020-07-21 eCollection Date: 2020-09-01 DOI: 10.1097/IM9.0000000000000034
Prasanth Manohar, Belinda Loh, Sebastian Leptihn
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引用次数: 0
Potential Therapeutic Options for COVID-19. COVID-19的潜在治疗方案
IF 2 Q3 INFECTIOUS DISEASES Pub Date : 2020-07-16 eCollection Date: 2020-09-01 DOI: 10.1097/IM9.0000000000000033
Xiaoqin Zheng, Lanjuan Li

The recently emerged coronavirus disease 2019 (COVID-19) has rapidly evolved into a pandemic with over 10 million infections and over 500 thousand deaths. There are currently no effective therapies or vaccines available to protect against this coronavirus infection. In this review, we discuss potential therapeutic options for COVID-19 based on the available information from previous research on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Substantial efforts are underway to discover new therapeutic agents for COVID-19, including the repurposing of existing agents and the development of novel agents that specifically target SARS-coronavirus 2 (SARS-CoV-2) or host factors. Through the screening of compound libraries, various classes of drugs, such as ribavirin, remdesivir, lopinavir/ritonavir, and hydroxychloroquine have been identified as potential therapeutic candidates against COVID-19. Novel antiviral drugs for SARS-coronavirus 2 are being developed to target viral enzymes or functional proteins, as well as host factors or cell signaling pathways.

最近出现的冠状病毒病2019 (COVID-19)已迅速演变为一场大流行,感染人数超过1000万,死亡人数超过50万。目前还没有有效的治疗方法或疫苗来预防这种冠状病毒感染。在这篇综述中,我们根据以往关于严重急性呼吸综合征(SARS)和中东呼吸综合征(MERS)的研究信息,讨论了COVID-19的潜在治疗方案。人们正在努力发现新的COVID-19治疗剂,包括重新利用现有药物和开发专门针对sars -冠状病毒2 (SARS-CoV-2)或宿主因子的新药。通过对化合物文库的筛选,确定了利巴韦林、瑞德西韦、洛匹那韦/利托那韦和羟氯喹等不同类别的药物是抗COVID-19的潜在候选药物。针对sars -冠状病毒2的新型抗病毒药物正在开发中,其目标是病毒酶或功能蛋白,以及宿主因子或细胞信号通路。
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引用次数: 0
Molecular Mechanisms of Gut Microbiota-Associated Colorectal Carcinogenesis 肠道微生物群与结直肠癌发生的分子机制
Q3 INFECTIOUS DISEASES Pub Date : 2020-06-24 DOI: 10.1097/IM9.0000000000000030
Yichang Shao, Xun Zeng
Abstract Colorectal cancer (CRC) is the cancer occurring in colon and rectum, and is the fourth leading cause of tumor-associated deaths worldwide. As a multi-etiological cancer, CRC could be induced by genetic and environmental factors, including unhealthy diet, irregular lifestyle, inappropriate inflammatory, and the dysbiosis of gut microbiota. Since immunotherapy has been the most popular cancer therapy nowadays, the relationships among gut microbiota, host immune cells and CRC pathogenesis are widely investigated. Scientists constantly tried to figure out the underlying mechanisms involved to support the further therapeutic studies. In this review, we discuss the component shifts of gut microbiota in CRC patients compared with healthy people, summarize how immune cells participate in protecting host from pathogenic microbes, elaborate the molecular mechanisms involved in gut microbiota-associated carcinogenesis of colonic epithelial cells and look into how gut microbiota influence the CRC therapy.
摘要癌症(CRC)是发生在结肠和直肠的癌症,是全球第四大肿瘤相关死亡原因。CRC作为一种多病因癌症,可能由遗传和环境因素诱导,包括不健康的饮食、不规律的生活方式、不适当的炎症和肠道微生物群的微生态失调。由于免疫疗法是目前最流行的癌症治疗方法,肠道微生物群、宿主免疫细胞和CRC发病机制之间的关系被广泛研究。科学家们不断试图找出相关的潜在机制,以支持进一步的治疗研究。在这篇综述中,我们讨论了CRC患者与健康人相比肠道微生物群的成分变化,总结了免疫细胞如何参与保护宿主免受病原微生物的侵害,阐述了肠道微生物群相关结肠上皮细胞癌变的分子机制,并探讨了肠道微生物组如何影响CRC治疗。
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引用次数: 1
Impact of Population Mask Wearing on Covid-19 Post Lockdown. 人口戴口罩对封锁后新冠肺炎的影响
IF 2 Q3 INFECTIOUS DISEASES Pub Date : 2020-06-05 DOI: 10.1097/IM9.0000000000000029
Babak Javid, Nathalie Q Balaban
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引用次数: 0
Transcriptomics Curation of SARS-CoV-2 Related Host Genes in Mice With COVID-19 Comorbidity: A Pilot Study. COVID-19合并症小鼠中SARS-CoV-2相关宿主基因的转录组学调控:一项初步研究
Q3 INFECTIOUS DISEASES Pub Date : 2020-05-06 eCollection Date: 2020-06-01 DOI: 10.1097/IM9.0000000000000025
Kunkai Su, Xin Huang, Kaijin Xu, Weibo Du, Danhua Zhu, Meifang Yang, Wenji Yuan, Lanjuan Li

The pandemic of coronavirus disease 2019 (COVID-19), a respiratory disease caused by a novel severe acute respiratory syndrome coronavirus-2, is causing substantial morbidity and mortality. Along with the respiratory symptoms, underlying diseases in senior patients, such as diabetes, hypertension, and coronary heart disease, are the most common comorbidities, which cause more severe outcomes and even death. During cellular attachment and entry of severe acute respiratory syndrome coronavirus-2, the key protein involved is the angiotensin I converting enzyme 2 (ACE2), which is located on the membrane of host cells. Here, we aim to curate an expression profile of Ace2 and other COVID-19 related genes across the available diabetes murine strains. Based on strictly manual curation and bioinformatics analysis of the publicly deposited expression datasets, Ace2 and other potentially involved genes such as Furin, Tmprss2, Ang, and Ang2 were examined. We found that Ace2 expression is rather ubiquitous in three selected diabetes prone strains (db/db, ob/ob and diet-induced obese). With the most abundant datasets present, the liver shows a medium Ace2 expression level compared with the lungs, pancreatic islets, brain and even T cells. Age is a more critical factor for Ace2 expression in db/db compared with the other two strains. Besides Ace2, the other four host genes showed varied levels of correlation to each other. To accelerate research on the interaction between COVID-19 and underlying diseases, the Murine4Covid transcriptomics database (www.geneureka.org/Murine4Covid) will facilitate the design of research on COVID-19 and comorbidities.

2019冠状病毒病(COVID-19)是一种由新型严重急性呼吸综合征冠状病毒-2引起的呼吸道疾病,其发病率和死亡率都很高。除了呼吸道症状外,糖尿病、高血压、冠心病等老年患者的潜在疾病是最常见的合并症,这些合并症会导致更严重的后果,甚至死亡。在严重急性呼吸综合征冠状病毒-2的细胞附着和进入过程中,参与的关键蛋白是位于宿主细胞膜上的血管紧张素I转换酶2 (ACE2)。在这里,我们的目标是在可用的糖尿病小鼠品系中整理Ace2和其他COVID-19相关基因的表达谱。基于对公开保存的表达数据集的严格手工整理和生物信息学分析,Ace2和其他可能涉及的基因如Furin、Tmprss2、Ang和Ang2进行了检测。我们发现Ace2在三种糖尿病易感菌株(db/db, ob/ob和饮食诱导的肥胖)中普遍表达。根据目前最丰富的数据集,与肺、胰岛、脑甚至T细胞相比,肝脏显示出中等水平的Ace2表达。与其他菌株相比,年龄是影响Ace2表达(db/db)的关键因素。除Ace2外,其余4个宿主基因均表现出不同程度的相关性。为了加速研究COVID-19与基础疾病之间的相互作用,Murine4Covid转录组学数据库(www.geneureka.org/Murine4Covid)将促进COVID-19及其合并症的研究设计。
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引用次数: 0
Suspected Close Contacts as the Pilot Indicator of the Growth Trend of Confirmed Population During the COVID-19 Pandemic: A Simulation Approach. 疑似密切接触者作为新冠肺炎大流行期间确诊人口增长趋势的试点指标:一种模拟方法
IF 2 Q3 INFECTIOUS DISEASES Pub Date : 2020-05-05 DOI: 10.1097/IM9.0000000000000026
Sisi Huang, Anding Zhu, Yan Wang, Yancong Xu, Lu Li, Dexing Kong

Background: Regarding to the actual situation of the new coronavirus disease 2019 epidemic, social factors should be taken into account and the increasing growth trend of confirmed populations needs to be explained. A proper model needs to be established, not only to simulate the epidemic, but also to evaluate the future epidemic situation and find a pilot indicator for the outbreak.

Methods: The original susceptible-infectious-recover model is modified into the susceptible-infectious-quarantine-confirm-recover combined with social factors (SIDCRL) model, which combines the natural transmission with social factors such as external interventions and isolation. The numerical simulation method is used to imitate the change curve of the cumulative number of the confirmed cases and the number of cured patients. Furthermore, we investigate the relationship between the suspected close contacts (SCC) and the final outcome of the growth trend of confirmed cases with a simulation approach.

Results: This article selects four representative countries, that is, China, South Korea, Italy, and the United States, and gives separate numerical simulations. The simulation results of the model fit the actual situation of the epidemic development and reasonable predictions are made. In addition, it is analyzed that the increasing number of SCC contributes to the epidemic outbreak and the prediction of the United States based on the population of the SCC highlights the importance of external intervention and active prevention measures.

Conclusions: The simulation of the model verifies its reliability and stresses that observable variable SCC can be taken as a pilot indicator of the coronavirus disease 2019 pandemic.

摘要背景:关于2019新型冠状病毒病疫情的实际情况,需要考虑社会因素,并解释确诊人口的增长趋势。需要建立一个适当的模型,不仅要模拟疫情,还要评估未来的疫情,并为疫情的爆发找到一个试点指标。方法:将原来的易感传染病康复模型修改为易感传染检疫确认康复与社会因素相结合(SIDCRL)模型,该模型将自然传播与外部干预、隔离等社会因素相融合。采用数值模拟方法模拟累计确诊病例数和治愈人数的变化曲线。此外,我们采用模拟方法研究了疑似密切接触者(SCC)与确诊病例增长趋势的最终结果之间的关系。结果:本文选取了中国、韩国、意大利和美国四个具有代表性的国家,分别进行了数值模拟。模型的仿真结果符合疫情发展的实际情况,并做出了合理的预测。此外,据分析,SCC数量的增加导致了疫情的爆发,美国基于SCC人口的预测突出了外部干预和积极预防措施的重要性。结论:该模型的模拟验证了其可靠性,并强调可观察变量SCC可以作为2019冠状病毒病大流行的试点指标。
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引用次数: 0
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Infectious microbes & diseases
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