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1. chinaXiv:202002.00078 [pdf]

Confirmed asymptomatic carrier of SARS-CoV-2

Luo, Sihui; Liu, Wei; Liu, Zhenjun; Zheng, Xueying; Ling, Ping; Ding, Yu; Hong, Changxing; Liu, Zhirong; Liu, Jian; Weng, Jianping
Subjects: Medicine, Pharmacy >> Clinical Medicine

Here we reported a case of asymptomatic carrier of SARS-CoV-2 infection. A 50-year old woman, lived with her husband in Anqing(Anhui, China) with no significant past medical history, travel history to Wuhan or adjacent area, or exposure to wild animals. She took throat swab test for SARS-CoV-2 nucleic acid due to her husband’s close contact with patients who had SARS-CoV-2 infection. Her results were confirmed positive on February 6, 2020. But she did not report elevation of temperature measurement, nor respiratory or gastrointestinal symptoms and her chest CT scan showed no significant abnormalities. She was hospitalized on February 6 and treated with antiviral agents. During her hospitalization, apart from a mild elevation of liver enzymes after 10-day treatment of lopinavir/ritonavir, she was asymptomatic, with her blood cell count, live and renal function largely normal. Her subcutaneous oxygen saturation stayed above 97%. Chest CT scan was repeated on February 11 and 20, and both were negative for signs of viral pneumonia. Notably, a second set of throat swabs and anal swabs were sent to test for SARS-CoV-2 on February 19, and the results were still confirmed positive. This is a confirmed case of asymptomatic carrier of SARS-CoV-2 infection. Her persistent positive findings in both throat and anal swabs suggested the possibility of healthy carrier of the virus, which adds to the difficulty in preventing transmission of the disease.

submitted time 2020-02-28 Hits947Downloads259 Comment 0

2. chinaXiv:202002.00080 [pdf]

Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia

Zikuan Leng; Rongjia Zhu; Wei Hou; Yingmei Feng; Hongjian Liu; Ronghua Jin; Kunlin Jin; Robert Chunhua Zhao
Subjects: Medicine, Pharmacy >> Clinical Medicine

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China, Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improve the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China from Jan 23, 2020. to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients with COVID-19 pneumonia in 14 days without observed adverse effect. The pulmonary function and symptoms of all patients with COVID-19 pneumonia were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells were disappeared in 3-6 days. And a group of CD14+CD11c+CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level TNF-α is significantly decreased while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

submitted time 2020-02-28 Hits187Downloads48 Comment 0

3. chinaXiv:202002.00079 [pdf]

基于移动平均预测限预判新型冠状病毒感染疫情趋势与适时风险分级

何豪; 何韵婷; 翟晶; 王筱金; 王炳顺
Subjects: Medicine, Pharmacy >> Preventive Medicine and Hygienics

目的 建立一种数据驱动的实用方法预测突发全新传染性疾病的疫情趋势,通过动态预判疫情风险与分级为防控策略提供量化依据。 方法 在移动平均法的基础上予以改进,提出一种移动平均预测限(Moving Average Prediction Limits, MAPL)方法,采用既往重症急性呼吸综合征(Severe Acute Respiratory Syndrome,SARS)疫情数据验证MAPL方法对疫情趋势和风险预判的实用性。追踪本次新型冠状病毒(COVID-19)感染疫情从2020年1月16日起的官方公布数据,采用MAPL方法预判疫情变动趋势与疫区适时风险分级。 结果 基于MAPL方法分析显示,2020年2月初全国COVID-19感染疫情达到峰值。经过前期积极防控,2月中旬起全国疫情整体呈下降趋势。到2月下旬各地疫情有明显的区域性差异。与湖北地区相比,非湖北地区新增病例数下降速度快且未来疫情加重的风险相对较小。在几个重要的疫情输入省份,新增确诊病例数和可疑病例数的发展趋势一致,但消减速度在各省份间存在差异。 结论 MAPL方法可以辅助判断疫情趋势并适时预判风险分级,各疫情输入区可结合当地实际与疫情风险分级规划落实差异化精准防控策略。

submitted time 2020-02-28 Hits174Downloads50 Comment 0

4. chinaXiv:202002.00085 [pdf]

晚期肺癌患者药物治疗前后尿蛋白质组的变化

张亚萌; 衡姊琦; 魏静; 王颖轶; 高友鹤
Subjects: Biology >> Biochemistry

肺癌作为一种严重威胁人类生命健康的疾病,尽管治疗方法种类较多,但如何把握治疗时机,为患者确定最有效的治疗用药仍然是一个难题。尿液蛋白质组可以敏感的反映机体的生理变化,有希望反映药物治疗后机体的病理或生理变化。为了研究晚期肺癌患者使用不同的药物进行治疗时其尿液蛋白质组的变化情况,通过收集晚期肺癌患者治疗前后的不同时间的尿液样本,使用液相色谱联用质谱(LC-MS / MS)来检测其尿蛋白组的变化。比较结果发现,当不同的患者使用不同药物治疗后,差异蛋白的变化各不相同,其差异蛋白反映的生物学过程变化和患者的临床表现变化较为一致。这项研究结果表明,(1)能够通过尿蛋白的变化反映不同药物治疗后患者的病理生理变化;(2)当不同患者使用相同药物治疗后,尿蛋白的变化能够反映出患者体内不同的病理生理变化,且和患者的临床病情评估结果较为一致。这些发现有可能为辅助临床治疗提供重要信息。

submitted time 2020-02-28 Hits2Downloads0 Comment 0

5. chinaXiv:202002.00082 [pdf]

ACE2 shedding and furin abundance in target organs may influence the efficiency of SARS-CoV-2 entry

Yuanchen Ma; Yinong Huang; Tao Wang; Andy Peng Xiang; Weijun Huang
Subjects: Medicine, Pharmacy >> Preclinical Medicine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified lineage B coronavirus, causing rapid worldwide outbreak of Corona Virus Disease 2019 (COVID-19). Despite genetically closed to SARS-CoV, SARS-CoV-2 seems to possess enhanced infectivity and subtle different clinical features, which may hamper the early screening of suspected patients as well as the control of virus transmission. Unfortunately, there are few tools to predict the potential target organ damage and possible clinical manifestations caused by such novel coronavirus. To solve this problem, we investigate the potential host cell entry mechanisms of SARS-CoV-2 through bioinformatics. Using the online single-cell sequence datasets, we analyze the expression of major receptor in host cells that mediates the virus entry, including angiotensin converting enzyme 2 (ACE2), and its co-expressed membrane endopeptidases. The results indicated the differential expression of ADAM10 and ADAM17 might contribute to the ACE2 shedding and affect the membrane ACE2 abundance. We further confirm a putative furin-cleavage site reported recently in the spike protein of SARS-CoV-2, which may facilitate the virus-cell fusion. Based on these findings, we develop a novel approach that comprehensively analyzed the virus receptor expression, ACE2 shedding, membrane fusion activity, virus uptake and virus replication to evaluate the infectivity of SARS-CoV-2 to different human organs. Our results indicate that, in addition to airway epithelia, cardiac tissue and enteric canals are susceptible to SARS-CoV-2 as well.

submitted time 2020-02-27 Hits60Downloads25 Comment 0

6. chinaXiv:202002.00076 [pdf]

瞳孔是心灵的窗口吗?——瞳孔在心理学研究中的应用及测量

杨晓梦; 王福兴; 王燕青; 赵婷婷; 高春颍; 胡祥恩
Subjects: Psychology >> Other Disciplines of Psychology

瞳孔大小是眼动研究中一个重要的参数指标,在一定程度上能够反映人的心理活动并影响他人的心理与行为。一方面,瞳孔变化受到自上而下的知觉与注意、情绪与动机、心理努力、社会认知与发展等因素的影响,另一方面,大瞳孔能引起他人更多的积极评价和积极行为。瞳孔的神经机制(蓝斑-去甲肾上腺素系统)和自适应增益理论解释了瞳孔与心理之间存在紧密联系的原因。瞳孔测量(pupillometry)作为一种有效的眼动追踪方法有助于理解瞳孔与心理的关系,研究者在测量瞳孔时需要关注无关变量(如亮度、注视位置),原始数据处理(如基线校正、眨眼处理)及瞳孔指标选取(如瞳孔直径、震颤频率)等问题,未来研究应继续探讨瞳孔与其他心理之间的关系,并探索更有效地处理和使用瞳孔指标的方法。

submitted time 2020-02-27 Hits45Downloads17 Comment 0

7. chinaXiv:202002.00083 [pdf]

新型冠状病毒肺炎中药天然产物、芳香产物计算筛选与文献证据集成

高敏; 朱月星; 熊江辉
Subjects: Medicine, Pharmacy >> Other Disciplines of Medicine and Pharmacology

药物重定位(老药新用)策略在新发传染病中具有独特应用前景。我们前期提出了一种新的药物重定位系统——aCODE,可以基于疾病流行早期有限信息对潜在有效的天然产物进行预测。本文基于计算工具与文献证据,对可能在新冠病毒肺炎(COVID-19)防治中发挥作用的中药天然产物进行理论研究,发现:(1)文献调研共发现56种经过实验验证具有抗冠状病毒活性的天然产物成分,可靶向冠状病毒的结构蛋白和非结构蛋白;(2)将aCODE系统所预测的抗冠状病毒天然产物成分与文献证据对比,发现交集有大黄素、甘草酸、人参皂苷R1、利血平和杨梅素等。大黄素可破坏冠状病毒S蛋白与宿主ACE2相互作用,阻止病毒入侵宿主细胞;同时具有抑制3a蛋白离子通道、阻止病毒释放的作用。甘草酸或其衍生物也是国内相关团队在新冠病毒肺炎治疗研究中重点关注的候选药物,已进入临床试验。(3)针对中药预测结果中大量出现的芳香化合物,aCODE系统增加芳香植物提取物数据源,计算发现氨基肉桂酸、肉桂醛、茴香烯、紫苏醇、芳樟醇、柠檬烯具有潜在的抗病毒效应。提示“芳香避秽”的细胞分子学机理值得进一步深入研究。aCODE系统的前期版本见:《一种新型冠状病毒肺炎COVID-19药物与天然产物快速发现的计算药理学方法》http://chinaxiv.org/abs/202002.00009。

submitted time 2020-02-27 Hits32Downloads268 Comment 0

8. chinaXiv:202002.00084 [pdf]

Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells

Bing Liang; Junhui Chen; Tao Li; Haiying Wu; Wenjie Yang; Yanjiao Li; Jianchun Li; Congtao Yu; Fangang Nie; Zhaoxia Ma; Mingxi Yang; Panrong Nie; Yanfeng Gao; Chuanyun Qian; Min Hu
Subjects: Medicine, Pharmacy >> Clinical Medicine

Background The COVID-19 cases increased very fast in the last two months. The mortality among critically ill patients, especially the elder ones, was relatively high. Considering that most of the dead patients were caused by severe inflammation response, it is very urgent to develop effective therapeutic agents and strategies for these patients. The human umbilical cord mesenchymal stem cells (hUCMSCs) have shown very good capability to modulate immune response and repair the injured tissue with good safety. Case Presentation Here, we reported the treatment process and clinical outcome of a 65-year-old female critically ill COVID-19 patient infected with 2019-nCoV (now called SARS-CoV-2). The significant clinical outcome and well tolerance was observed by the adoptive transfer of allogenic hUCMSCs. Conclusions Our results suggested that the adoptive transfer therapy of hUCMSCs might be an ideal choice to be used or combined with other immune modulating agents to treat the critically ill COVID-19 patients.

submitted time 2020-02-27 Hits110Downloads13 Comment 0

9. chinaXiv:202002.00081 [pdf]

SARS-coronavirus-2 nsp13 possesses NTPase and RNA helicase activities

Shu, Ting; Huang, Muhan; Wu, Di; Ren, Yujie; Zhang, Xueyi; Han, Yang; Mu, Jingfang; Wang, Ruibing; Qiu, Yang; Zhang, Ding-Yu; Zhou, Xi
Subjects: Biology >> Virology

The ongoing outbreak of Coronavirus Disease 2019 (Covid-19) emerged from Wuhan, Hubei, since December 2019 has become a global public health emergency. SARS-coronavirus-2 (SARS-CoV-2), the causative pathogen of Covid-19, is a positive-sense single-stranded RNA virus belonging to the family Coronaviridae. For RNA viruses, virus-encoded RNA helicases have long been recognized to play pivotal roles during viral life cycles by facilitating the correct folding and replication of viral RNAs. Here, our studies show that SARS-CoV-2-encoded nonstructural protein 13 (nsp13) possesses the nucleoside triphosphate hydrolase (NTPase) and RNA helicase activities that can hydrolyze all types of NTPs and unwind RNA helices dependently of the presence of NTP, and further characterize the biochemical characteristics of these two enzymatic activities associated with SARS-CoV-2 nsp13. Moreover, we found that some bismuth salts could effectively inhibit both the NTPase and RNA helicase activities of SARS-CoV-2 nsp13 in a dose-dependent manner. Thus, our findings demonstrate the NTPase and helicase activities of SARS-CoV-2 nsp13, which may play an important role in SARS-CoV-2 replication and serve as a target for antivirals.

submitted time 2020-02-27 Hits78Downloads19 Comment 0

10. chinaXiv:202002.00074 [pdf]

Molecular karyotypes of loquat (Eriobotrya japonica) aneuploids can be detected by using SSR markers combined with quantitative PCR irrespective of heterozygosity

Wen, Guo; Dang, Jiangbo; Xie, Zhongyi; Wang, Jinying; Jiang, Pengfei; Guo, Qigao; Liang, Guolu
Comment:This article has been published online in Plant Methods
Subjects: Biology >> Botany
Subjects: Agriculture, Forestry,Livestock & Aquatic Products Science >> Horticulture

Background: Aneuploidy, a condition caused by an imbalance between the relative dosages of chromosomes, generally produces a novel phenotype specific to the molecular karyotype. Few techniques are currently available for detecting the molecular karyotypes of aneuploids in plants. Methods: By PCR amplification of 209 pairs of SSR primers, 17 pairs of SSR primers with no polymorphism and stable amplification in 23 different ploidy loquat were screened out. Seventeen SSR markers combined with qPCR for detection of aneuploid loquat H39 (2n=2x+5=39) karyotype variation. To verify the method for detection of aneuploid karyotype variation, 9 hybrid offspring of Q24 × ‘Huabai No. 1’ and 16 open-pollination progeny of the triploid loquat A313 and A322 were obtained, and we detected their chromosome numbers using conventional cytological methods. The SSR-qPCR method was used to detect the molecular karyotypes of aneuploids in the 9 hybrid offspring of Q24 × ‘Huabai No. 1’ and 16 open-pollination progeny of the triploid loquat A313 and A322. Results: Based on this imbalance in chromosome dosage, a new approach (referred to as ‘SSR-qPCR’) combining simple sequence repeat (SSR) markers and quantitative real-time PCR (qPCR) has been developed and utilized to detect some common aneuploids irrespective of heterozygosity. We screened 17 specific SSR markers covering all loquat linkage groups and redesigned 6 pairs of primers for SSR markers that can detect loquat chromosome aneuploidies. The SSR-qPCR detection results obtained for hybrid progeny and open-pollination progeny of triploid loquat showed diagnostic accuracies of 88.9% and 62.5%, respectively, compared with the chromosome preparation results. Limitations: Loquat genome sequences have not been published, available SSR markers are currently limited. Conclusion: SSR-qPCR can detect loquat aneuploids and be used to construct the entire molecular karyotypes of aneuploid individuals. Therefore, this method offers a novel alternative for the detection of chromosome aneuploidies.

submitted time 2020-02-27 Hits70Downloads14 Comment 0

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