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Article ; Online: Overview on the use of IL-6 agents in the treatment of patients with cytokine release syndrome (CRS) and pneumonitis related to COVID-19 disease.

Zhou, Zeyun / Price, Christina C

2020 Volume 29, Issue 12, Page(s) 1407–1412

Abstract: Introduction: A novel coronavirus pneumonia (COVID-19) has caused significant life loss and healthcare burden globally. COVID-19 is known to cause a cytokine release syndrome (CRS) like response, and interleukin-6 (IL-6) is one of the cytokines involved. ...

Abstract	Introduction: A novel coronavirus pneumonia (COVID-19) has caused significant life loss and healthcare burden globally. COVID-19 is known to cause a cytokine release syndrome (CRS) like response, and interleukin-6 (IL-6) is one of the cytokines involved. Clinicians are using IL-6 inhibitors to CRS, and researchers are investigating the use of IL-6 inhibitors, namely tocilizumab, sarilumab, siltuximab, in COVID-19 management. Areas covered: In this article, we will discuss the pharmacology of these three inhibitors and summarize available clinical data via literature search on PubMed with keywords of tocilizumab, sarilumab, siltuximab, and COVID-19. While awaiting more data from randomized clinical trials on these drugs, observational studies and clinical reports have demonstrated IL-6 inhibitors showed some benefits in improving clinical outcome and a well-tolerated safety profile. Expert opinion: There is a role for suppressing the immune response with IL-6 inhibitors that will continue to require investigation. These agents are available and have demonstrated a mild safety profile. There may be advantages to a targeted approach to suppressing the hyperinflammatory state of the disease. Timing, the long-term effects, and what cocktail of medications demonstrates the strongest outcomes are all important considerations as IL-6 inhibitors continue to be evaluated in this global pandemic.
MeSH term(s)	Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized/administration & dosage ; COVID-19/drug therapy ; COVID-19/epidemiology ; COVID-19/immunology ; Clinical Trials as Topic/methods ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/epidemiology ; Cytokine Release Syndrome/immunology ; Humans ; Interleukin-6/antagonists & inhibitors ; Interleukin-6/immunology ; Pneumonia/drug therapy ; Pneumonia/epidemiology ; Pneumonia/immunology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; IL6 protein, human ; Interleukin-6 ; tocilizumab (I031V2H011) ; sarilumab (NU90V55F8I) ; siltuximab (T4H8FMA7IM)
Keywords	covid19
Language	English
Publishing date	2020-12-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1182884-5
ISSN	1744-7658 ; 0967-8298 ; 1354-3784
ISSN (online)	1744-7658
ISSN	0967-8298 ; 1354-3784
DOI	10.1080/13543784.2020.1840549
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Article ; Online: Discovery of Novel 3-Hydroxyquinazoline-2,4(1 H ,3 H )-Dione Derivatives

Yang Cao / Abudumijiti Aimaiti / Zeyun Zhu / Lu Zhou / Deyong Ye

International Journal of Molecular Sciences, Vol 23, Iss 5930, p

A Series of Metal Ion Chelators with Potent Anti-HCV Activities

2022 Volume 5930

Abstract: Millions of people worldwide suffer from acute or chronic liver inflammation caused by the hepatitis C virus (HCV). Metal ion chelators have achieved widespread success in the development of antiviral drugs. Some inhibitors with metal ion chelating ... ...

Abstract	Millions of people worldwide suffer from acute or chronic liver inflammation caused by the hepatitis C virus (HCV). Metal ion chelators have achieved widespread success in the development of antiviral drugs. Some inhibitors with metal ion chelating structures have been proven to have good inhibitory activities on non-structural protein 5B (NS5B) polymerase. However, most of the reported metal ion chelators showed poor anti-HCV potency at the cellular level. Hence, we designed and synthesized a series of 3-hydroxyquinazoline-2,4(1 H ,3 H )-dione derivatives with novel metal ion chelating structures. Typical compounds such as 21h , 21k, and 21t showed better anti-HCV activities than ribavirin with EC 50 values less than 10 μM. 21t is currently known as one of the metal ion chelators with the best anti-HCV potency (EC 50 = 2.0 μM) at the cellular level and has a better therapeutic index (TI > 25) as compared to ribavirin and the reported compound 6 . In the thermal shift assay, the representative compounds 21e and 21k increased the melting temperature ( T m ) of NS5B protein solution by 1.6 °C and 2.1 °C, respectively, at the test concentration, indicating that these compounds may exert an anti-HCV effect by targeting NS5B. This speculation was also supported by our molecular docking studies and ultraviolet-visible (UV-Vis) spectrophotometry assay, in which the possibility of binding of 3-hydroxyquinazoline-2,4(1 H ,3 H )-diones with Mg 2+ in the NS5B catalytic center was observed.
Keywords	chelator ; NS5B ; anti-HCV ; hydroxyquinazolinedione ; synthesis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	540
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Complementing the US Food and Drug Administration Adverse Event Reporting System With Adverse Drug Reaction Reporting From Social Media: Comparative Analysis.

Zhou, Zeyun / Hultgren, Kyle Emerson

JMIR public health and surveillance

2020 Volume 6, Issue 3, Page(s) e19266

Abstract: Background: Adverse drug reactions (ADRs) can occur any time someone uses a medication. ADRs are systematically tracked and cataloged, with varying degrees of success, in order to better understand their etiology and develop methods of prevention. The ... ...

Abstract	Background: Adverse drug reactions (ADRs) can occur any time someone uses a medication. ADRs are systematically tracked and cataloged, with varying degrees of success, in order to better understand their etiology and develop methods of prevention. The US Food and Drug Administration (FDA) has developed the FDA Adverse Event Reporting System (FAERS) for this purpose. FAERS collects information from myriad sources, but the primary reporters have traditionally been medical professionals and pharmacovigilance data from manufacturers. Recent studies suggest that information shared publicly on social media platforms related to medication use could be of benefit in complementing FAERS data in order to have a richer picture of how medications are actually being used and the experiences people are having across large populations. Objective: The aim of this study is to validate the accuracy and precision of social media methodology and conduct evaluations of Twitter ADR reporting for commonly used pharmaceutical agents. Methods: ADR data from the 10 most prescribed medications according to pharmacy claims data were collected from both FAERS and Twitter. In order to obtain data from FAERS, the SafeRx database, a curated collection of FAERS data, was used to collect data from March 1, 2016, to March 31, 2017. Twitter data were manually scraped during the same time period to extract similar data using an algorithm designed to minimize noise and false signals in social media data. Results: A total of 40,539 FAERS ADR reports were obtained via SafeRx and more than 40,000 tweets containing the drug names were obtained from Twitter's Advanced Search engine. While the FAERS data were specific to ADRs, the Twitter data were more limited. Only hydrocodone/acetaminophen, prednisone, amoxicillin, gabapentin, and metformin had a sufficient volume of ADR content for review and comparison. For metformin, diarrhea was the side effect that resulted in no difference between the two platforms (P=.30). For hydrocodone/acetaminophen, ineffectiveness as an ADR that resulted in no difference (P=.60). For gabapentin, there were no differences in terms of the ADRs ineffectiveness and fatigue (P=.15 and P=.67, respectively). For amoxicillin, hypersensitivity, nausea, and rash shared similar profiles between platforms (P=.35, P=.05, and P=.31, respectively). Conclusions: FAERS and Twitter shared similarities in types of data reported and a few unique items to each data set as well. The use of Twitter as an ADR pharmacovigilance platform should continue to be studied as a unique and complementary source of information rather than a validation tool of existing ADR databases.
Language	English
Publishing date	2020-09-30
Publishing country	Canada
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2369-2960
ISSN (online)	2369-2960
DOI	10.2196/19266
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Article ; Online: Comparative analysis of genomic profiles between tissue-based and plasma-based next-generation sequencing in patients with non-small cell lung cancer.

Lin, Zeyun / Li, Yuqin / Tang, Shiqi / Deng, Qiuhua / Jiang, Juhong / Zhou, Chengzhi

Lung cancer (Amsterdam, Netherlands)

2023 Volume 182, Page(s) 107282

Abstract: Objectives: Genotype-guided personalized therapy has become an essential part of routine clinical care in non-small cell lung cancer (NSCLC) patients. However, small tissue specimens often yield inadequate molecular testing material. Plasma ctDNA-based ... ...

Abstract	Objectives: Genotype-guided personalized therapy has become an essential part of routine clinical care in non-small cell lung cancer (NSCLC) patients. However, small tissue specimens often yield inadequate molecular testing material. Plasma ctDNA-based liquid biopsy is an increasingly common non-invasive alternative to tissue biopsy. This study examined the similarities and differences in the molecular profiling of tissue and plasma samples to provide insight into sample selection in clinical practice. Materials and methods: Sequencing data from 190 NSCLC patients who underwent concurrent tissue-based next-generation sequencing (tissue-NGS) and plasma-based NGS (plasma-NGS) using a 168-gene panel were analyzed. Results: Tissue-NGS identified genomic alterations in 97.4% (185/190) of the enrolled patients and plasma-NGS identified genomic alterations in 72.1% (137/190) of the enrolled patients. Considering all NSCLC guideline-recommended biomarkers in the entire cohort of 190 cases, 81 patients had positive concordant mutations detected in both tissue and plasma samples, while 69 patients had no predefined alterations detected in either tissue or plasma samples. Additional mutations were found in the tissues of 34 patients and the plasma of six patients. The overall concordance rate between tissue and plasma samples was 78.9% (150/190). The tissue-NGS and plasma-NGS sensitivities were 95.0% and 71.9%, respectively. In the 137 patients with detectable ctDNA in plasma samples, the concordance rate between tissue and plasma samples reached 91.2%, and the sensitivity of plasma-NGS reached 93.5%. Conclusion: Our findings indicate that plasma-NGS is less capable of detecting genetic alterations than tissue-NGS, especially for copy number variations and gene fusions. Tissue-NGS remains the preferred method for evaluating the molecular profile of NSCLC patients when tumor tissue is available. We suggest that the concurrent use of liquid biopsy and tissue biopsy is the optimal approach in clinical practice; alternatively, plasma can be used as substitute material when tissue is unavailable.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Lung Neoplasms/drug therapy ; DNA Copy Number Variations ; Circulating Tumor DNA/genetics ; Mutation ; Genomics ; High-Throughput Nucleotide Sequencing/methods ; Biomarkers, Tumor/genetics
Chemical Substances	Circulating Tumor DNA ; Biomarkers, Tumor
Language	English
Publishing date	2023-06-22
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632771-0
ISSN	1872-8332 ; 0169-5002
ISSN (online)	1872-8332
ISSN	0169-5002
DOI	10.1016/j.lungcan.2023.107282
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Zs.A 2135: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Aberrant interhemispheric functional reciprocities of the default mode network and motor network in subcortical ischemic stroke patients with motor impairment: A longitudinal study.

Li, Yongxin / Yu, Zeyun / Zhou, Xuan / Wu, Ping / Chen, Jiaxu

Frontiers in neurology

2022 Volume 13, Page(s) 996621

Abstract: Purpose: The purpose of the present study was to explore the longitudinal changes in functional homotopy in the default mode network (DMN) and motor network and its relationships with clinical characteristics in patients with stroke.: Methods: ... ...

Abstract	Purpose: The purpose of the present study was to explore the longitudinal changes in functional homotopy in the default mode network (DMN) and motor network and its relationships with clinical characteristics in patients with stroke. Methods: Resting-state functional magnetic resonance imaging was performed in stroke patients with subcortical ischemic lesions and healthy controls. The voxel-mirrored homotopic connectivity (VMHC) method was used to examine the differences in functional homotopy in patients with stroke between the two time points. Support vector machine (SVM) and correlation analyses were also applied to investigate whether the detected significant changes in VMHC were the specific feature in patients with stroke. Results: The patients with stroke had significantly lower VMHC in the DMN and motor-related regions than the controls, including in the precuneus, parahippocampus, precentral gyrus, supplementary motor area, and middle frontal gyrus. Longitudinal analysis revealed that the impaired VMHC of the superior precuneus showed a significant increase at the second time point, which was no longer significantly different from the controls. Between the two time points, the changes in VMHC in the superior precuneus were significantly correlated with the changes in clinical scores. SVM analysis revealed that the VMHC of the superior precuneus could be used to correctly identify the patients with stroke from the controls with a statistically significant accuracy of 81.25% ( Conclusions: Our findings indicated that the increased VMHC in the superior precuneus could be regarded as the neuroimaging manifestation of functional recovery. The significant correlation and the discriminative power in classification results might provide novel evidence to understand the neural mechanisms responsible for brain reorganization after stroke.
Language	English
Publishing date	2022-10-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.996621
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Article ; Online: Discovery of Novel 3-Hydroxyquinazoline-2,4(1

Cao, Yang / Aimaiti, Abudumijiti / Zhu, Zeyun / Zhou, Lu / Ye, Deyong

International journal of molecular sciences

2022 Volume 23, Issue 11

Abstract	Millions of people worldwide suffer from acute or chronic liver inflammation caused by the hepatitis C virus (HCV). Metal ion chelators have achieved widespread success in the development of antiviral drugs. Some inhibitors with metal ion chelating structures have been proven to have good inhibitory activities on non-structural protein 5B (NS5B) polymerase. However, most of the reported metal ion chelators showed poor anti-HCV potency at the cellular level. Hence, we designed and synthesized a series of 3-hydroxyquinazoline-2,4(1H,3H)-dione derivatives with novel metal ion chelating structures. Typical compounds such as 21h, 21k, and 21t showed better anti-HCV activities than ribavirin with EC50 values less than 10 μM. 21t is currently known as one of the metal ion chelators with the best anti-HCV potency (EC50 = 2.0 μM) at the cellular level and has a better therapeutic index (TI > 25) as compared to ribavirin and the reported compound 6. In the thermal shift assay, the representative compounds 21e and 21k increased the melting temperature (Tm) of NS5B protein solution by 1.6 °C and 2.1 °C, respectively, at the test concentration, indicating that these compounds may exert an anti-HCV effect by targeting NS5B. This speculation was also supported by our molecular docking studies and ultraviolet-visible (UV-Vis) spectrophotometry assay, in which the possibility of binding of 3-hydroxyquinazoline-2,4(1H,3H)-diones with Mg2+ in the NS5B catalytic center was observed.
MeSH term(s)	Antiviral Agents/therapeutic use ; Chelating Agents/pharmacology ; Hepacivirus ; Hepatitis C/drug therapy ; Humans ; Molecular Docking Simulation ; Ribavirin/pharmacology ; Viral Nonstructural Proteins/metabolism
Chemical Substances	Antiviral Agents ; Chelating Agents ; Viral Nonstructural Proteins ; Ribavirin (49717AWG6K)
Language	English
Publishing date	2022-05-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23115930
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Article ; Online: Overview on the use of IL-6 agents in the treatment of patients with cytokine release syndrome (CRS) and pneumonitis related to COVID-19 disease

Zhou, Zeyun / Price, Christina C.

Expert Opinion on Investigational Drugs ; ISSN 1354-3784 1744-7658

2020

Keywords	Pharmacology (medical) ; Pharmacology ; General Medicine ; covid19
Language	English
Publisher	Informa UK Limited
Publishing country	uk
Document type	Article ; Online
DOI	10.1080/13543784.2020.1840549
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pijx confers broad-spectrum seedling and panicle blast resistance by promoting the degradation of ATP β subunit and OsRbohC-mediated ROS burst in rice.

Xiao, Ning / Wu, Yunyu / Zhang, Xiaoxiang / Hao, Zeyun / Chen, Zichun / Yang, Zefeng / Cai, Yue / Wang, Ruyi / Yu, Ling / Wang, Zhiping / Lu, Yue / Shi, Wei / Pan, Cunhong / Li, Yuhong / Zhou, Changhai / Liu, Jianju / Huang, Niansheng / Liu, Guangqing / Ji, Hongjuan /

Zhu, Shuhao / Fang, Shuai / Ning, Yuese / Li, Aihong

Molecular plant

2024 Volume 17, Issue 4, Page(s) 672–675

Language	English
Publishing date	2024-02-23
Publishing country	England
Document type	Published Erratum
ZDB-ID	2393618-6
ISSN	1752-9867 ; 1674-2052
ISSN (online)	1752-9867
ISSN	1674-2052
DOI	10.1016/j.molp.2024.02.013
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Article ; Online: The analysis and optimization of thermal sensation of train drivers under occupational thermal exposure

Zeyun Yang / Wenjun Zhou / Gang Xu / Xinkang Li / Mingzhi Yang / Qiang Xiao / Chaojie Fan / Yong Peng

Frontiers in Public Health, Vol

2023 Volume 11

Abstract: IntroductionProlonged exposure of train drivers to thermal discomfort can lead to occupational safety and health (OSH) risks, causing physical and mental injuries. Traditional method of treating human skin as a wall surface fail to observe accurate skin ... ...

Abstract	IntroductionProlonged exposure of train drivers to thermal discomfort can lead to occupational safety and health (OSH) risks, causing physical and mental injuries. Traditional method of treating human skin as a wall surface fail to observe accurate skin temperature changes or obtain human thermal comfort that adapts to the thermal environment.MethodsThis study employs the Stolwijk human thermal regulation model to investigate and optimize the thermal comfort of train drivers. To minimize the time-consuming design optimization, a pointer optimization algorithm based on radial basis function (RBF) approximation was utilized to optimize the train cab ventilation system design and enhance drivers’ thermal comfort. The train driver thermal comfort model was developed using Star-CCM+ and 60 operating conditions were sampled using an Optimal Latin Hypercube Design (Opt LHD).Results and DiscussionWe analyzed the effects of air supply temperature, air supply volume, air supply angle, solar radiation intensity and solar altitude angle on the local thermal sensation vote (LTSV) and overall thermal sensation vote (OTSV) of the train driver. Finally, the study obtained the optimal air supply parameters for the Heating Ventilation and Air Conditioning (HVAC) in the train cabin under extreme summer conditions, effectively improving the thermal comfort of the driver.
Keywords	train driver ; thermal sensation ; occupational thermal exposure ; design and optimization ; air supply parameters ; human thermal regulation model ; Public aspects of medicine ; RA1-1270
Subject code	690
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The analysis and optimization of thermal sensation of train drivers under occupational thermal exposure.

Yang, Zeyun / Zhou, Wenjun / Xu, Gang / Li, Xinkang / Yang, Mingzhi / Xiao, Qiang / Fan, Chaojie / Peng, Yong

Frontiers in public health

2023 Volume 11, Page(s) 1164817

Abstract: Introduction: Prolonged exposure of train drivers to thermal discomfort can lead to occupational safety and health (OSH) risks, causing physical and mental injuries. Traditional method of treating human skin as a wall surface fail to observe accurate ... ...

Abstract	Introduction: Prolonged exposure of train drivers to thermal discomfort can lead to occupational safety and health (OSH) risks, causing physical and mental injuries. Traditional method of treating human skin as a wall surface fail to observe accurate skin temperature changes or obtain human thermal comfort that adapts to the thermal environment. Methods: This study employs the Stolwijk human thermal regulation model to investigate and optimize the thermal comfort of train drivers. To minimize the time-consuming design optimization, a pointer optimization algorithm based on radial basis function (RBF) approximation was utilized to optimize the train cab ventilation system design and enhance drivers' thermal comfort. The train driver thermal comfort model was developed using Star-CCM+ and 60 operating conditions were sampled using an Optimal Latin Hypercube Design (Opt LHD). Results and discussion: We analyzed the effects of air supply temperature, air supply volume, air supply angle, solar radiation intensity and solar altitude angle on the local thermal sensation vote (LTSV) and overall thermal sensation vote (OTSV) of the train driver. Finally, the study obtained the optimal air supply parameters for the Heating Ventilation and Air Conditioning (HVAC) in the train cabin under extreme summer conditions, effectively improving the thermal comfort of the driver.
MeSH term(s)	Humans ; Temperature ; Skin Temperature ; Air Conditioning/methods ; Heating ; Thermosensing
Language	English
Publishing date	2023-06-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2023.1164817
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