Publications by authors named "Jun Wan"

525 Publications

Analysis of right ventricular flow with 4-dimensional flow cardiovascular magnetic resonance imaging in patients with pulmonary arterial hypertension.

Quant Imaging Med Surg 2021 Aug;11(8):3655-3665

Siemens Shenzhen Magnetic Resonance Ltd., Shenzhen, China.

Background: Cardiac flow closely interact with function, however, the correlation of right ventricular (RV) flow and function remains unknown, thus our objective is to observe right ventricular flow with four-dimensional phase-contrast cardiovascular magnetic resonance imaging (4D flow CMR) in patients with pulmonary arterial hypertension (PAH) and to analyze flow components with RV function and hemodynamics.

Methods: This study retrospectively enrolled 30 patients with PAH (mean age: 49±13 years, 16 females) and 14 age- and sex-matched healthy volunteers as controls (mean age: 44±12 years, 9 females). All patients who underwent CMR and right heart catheterization (RHC) within 1 week between January 2019 and July 2020 were included. Hemodynamics were measured with RHC. RV flow components, including the percentages of direct flow (RVPDF), retained inflow (RVPRI), delayed ejection flow (RVPDEF) and residual volume (RVPRVo) were quantified using 4D flow CMR. The associations between RV flow components and other CMR metrics, clinical data, and hemodynamics were analyzed by Spearman's correlation analysis.

Results: In patients with PAH, RVPDF was decreased and RVPRVo was increased compared with the normal control group. The sum of RVPDF and RVPDEF RV was significantly correlated with RV ejection fraction (RVEF) (r=0.802, P<0.001), and there was no notable difference between RVEF and the sum of RVPDF and RVPDEF (t=0.251, P=0.831). Both RVPDF and RVPRVo were correlated (in opposite directions) with the RV end-diastolic volume index, RV end-systolic volume index, RV global longitudinal strain, and RVEF. RVPDF was negatively correlated with pulmonary vascular resistance (PVR), and positively correlated with cardiac output and cardiac index. RVPRVo was positively correlated with PVR and negatively correlated with cardiac output and cardiac index.

Conclusions: RV blood flow components qualified with 4D flow CMR is a valuable noninvasive method for the assessment of RV function and hemodynamics in patients with PAH.
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http://dx.doi.org/10.21037/qims-20-1267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245951PMC
August 2021

Changes in Expressions of HSP27, HSP70, and Soluble Glycoprotein in Heart Failure Rats Complicated with Pulmonary Edema and Correlations with Cardiopulmonary Functions.

Biomed Res Int 2021 19;2021:6733341. Epub 2021 Jul 19.

Department of Cardiac Surgery, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, 518020 Guangdong, China.

The study is aimed at investigating the changes in expressions of heat shock protein 27 (HSP27), HSP70, and soluble glycoprotein (SGP) in heart failure (HF) rats complicated with pulmonary edema and exploring their potential correlations with cardiopulmonary functions. The rat model of HF was established, and the rats were divided into HF model group (model group, = 15) and normal group ( = 15). After successful modeling, MRI and ECG were applied to detect the cardiac function indexes of the rats. The myocardial function indexes were determined, the injury of myocardial tissues was observed via hematoxylin and eosin (HE) staining, and the content of myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-alpha (TNF-) in the blood was measured. The partial pressure of oxygen (PaO) and oxygenation index (OI) were observed, and the airway resistance and lung compliance were examined. Moreover, quantitative polymerase chain reaction (qPCR) and Western blotting assay were performed to detect the gene and protein expression levels of HSP27, HSP70, and SGP130. The levels of serum creatine kinase (CK), creatine (Cr), and blood urea nitrogen (BUN) were increased markedly in model group ( < 0.05). Model group had notably decreased fractional shortening (FS) and ejection fraction (EF) compared with normal group ( < 0.05), while the opposite results of left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were detected. In model group, the content of serum MPO, MMP-9, and TNF- was raised remarkably ( < 0.05), OI and PaO were reduced notably ( < 0.05), the airway resistance was increased ( < 0.05), and the lung compliance was decreased ( < 0.05). Obviously elevated gene and protein expression levels of HSP27, HSP70, and SGP130 were detected in model group ( < 0.05). The expressions of HSP27, HSP70, and SGP130 are increased in HF rats complicated with pulmonary edema, seriously affecting the cardiopulmonary functions of the rats.
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http://dx.doi.org/10.1155/2021/6733341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315849PMC
July 2021

CircRtn4 Acts as the Sponge of miR-24-3p to Promote Neurite Growth by Regulating CHD5.

Front Mol Neurosci 2021 7;14:660429. Epub 2021 Jul 7.

Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.

Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules. After derived from precursor mRNA back-splicing, circRNAs play important roles in many biological processes. Recently, it was shown that several circRNAs were enriched in the mammalian brain with unclear functions. The expression of circRtn4 in the mouse brain was increased with the differentiation of primary neurons. In our study, knockdown of circRtn4 inhibited neurite growth, while overexpression of circRtn4 significantly increased neurite length. By dual-luciferase reporter assay and RNA antisense purification assay, circRtn4 was identified as a miRNA sponge for miR-24-3p. Moreover, knockdown of miR-24-3p increased neurite length, while overexpression of miR-24-3p significantly inhibited neurite growth. Furthermore, CHD5 was confirmed to be a downstream target gene of miR-24-3p. And CHD5 silence counteracted the positive effect of circRtn4 overexpression on neurite growth. In conclusion, circRtn4 may act as the sponge for miR-24-3p to promote neurite growth by regulating CHD5.
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http://dx.doi.org/10.3389/fnmol.2021.660429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294096PMC
July 2021

Deletion Aggravates Sepsis-Induced Cardiac Dysfunction by Regulating Macrophage Polarization.

Front Pharmacol 2021 2;12:632912. Epub 2021 Jul 2.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Cardiac dysfunction is a well-recognized complication of sepsis and is associated with the outcome and prognosis of septic patients. Evidence suggests that participates in the regulation of various cardiovascular diseases, including heart failure, hypertension and acute myocardial infarction. However, the effects of in sepsis-induced cardiac dysfunction remain unknown. In our study, lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) model were used to mimic sepsis, and cardiac expression was assessed. In addition, knockout mice were used to detect the role of in sepsis-related cardiac dysfunction. We observed for the first time that expression is upregulated in mice after LPS treatment and macrophages were the main sources of In addition, our findings demonstrated that deletion aggravates LPS-induced cardiac dysfunction and injury, as evidenced by the increased serum and cardiac levels of lactate dehydrogenase (LDH) and cardiac creatine kinase-myocardial band (CK-MB). Moreover, deletion enhances LPS-induced macrophage accumulation and drives macrophages toward the M1 phenotype in LPS-treated mice. deletion also downregulated the activity of AMP-activated protein kinase (AMPK) but increased the phosphorylation levels of p65 (p-p65) and NF-κB inhibitor alpha (p-IκBα). In addition, deletion aggravates CLP-induced cardiac dysfunction and injury. Treatment with the AMPK activator AICAR abolishes the deterioration effect of deletion on LPS-induced cardiac dysfunction. In conclusion, deletion aggravated LPS-induced cardiac dysfunction and injury by exacerbating the imbalance of M1 and M2 macrophages. Our data provide evidence that may represent an attractive target for sepsis-induced cardiac dysfunction.
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http://dx.doi.org/10.3389/fphar.2021.632912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284189PMC
July 2021

Updated SARS-CoV-2 single nucleotide variants and mortality association.

J Med Virol 2021 Jul 10. Epub 2021 Jul 10.

Department of BioHealth Informatics, Indiana University School of Informatics and Computing, Indiana University - Purdue University Indianapolis, Indianapolis, Indiana, USA.

By analyzing newly collected SARS-CoV-2 genomes and comparing them with our previous study about SARS-CoV-2 single nucleotide variants (SNVs) before June 2020, we found that the SNV clustering had changed remarkably since June 2020. Apart from that the group of SNVs became dominant, which is represented by two nonsynonymous mutations A23403G (S:D614G) and C14408T (ORF1ab:P4715L), a few emerging groups of SNVs were recognized with sharply increased monthly incidence ratios of up to 70% in November 2020. Further investigation revealed sets of SNVs specific to patients' ages and/or gender, or strongly associated with mortality. Our logistic regression model explored features contributing to mortality status, including three critical SNVs, G25088T(S:V1176F), T27484C (ORF7a:L31L), and T25A (upstream of ORF1ab), ages above 40 years old, and the male gender. The protein structure analysis indicated that the emerging subgroups of nonsynonymous SNVs and the mortality-related ones were located on the protein surface area. The clashes in protein structure introduced by these mutations might in turn affect the viral pathogenesis through the alteration of protein conformation, leading to a difference in transmission and virulence. Particularly, we explored the fact that nonsynonymous SNVs tended to occur in intrinsic disordered regions of Spike and ORF1ab to significantly increase hydrophobicity, suggesting a potential role in the change of protein folding related to immune evasion.
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http://dx.doi.org/10.1002/jmv.27191DOI Listing
July 2021

Regulating the Self-Discharge of Flexible All-Solid-State Supercapacitors by a Heterogeneous Polymer Electrolyte.

Small 2021 Jul 9:e2102054. Epub 2021 Jul 9.

Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, China.

Supercapacitors with high power density and an ultralong cyclic lifetime have been intensively investigated. However, the crucial challenge of their rapid self-discharge process is often neglected in most cases. A heterogeneous interface formed between two layers of polymer electrolytes is designed, in which a polyanion and a polycation are added into a common matrix of polymer electrolyte, respectively. By using the heterogeneous polymer electrolyte (HPE) as the separator simultaneously, the resultant supercapacitors exhibit comparable electrochemical performance to that of devices based on traditional polymer electrolytes. The HPE-based supercapacitors using both electric double-layer capacitive and pseudocapacitive electrodes show at least one time longer self-discharge time than that of devices based on homogenous polymer electrolyte, especially for the electrode in an electrolyte containing polyanion served as a positive pole during the charging process. Because of the same polymer matrix used, the heterojunction structure of the HPE exhibits excellent stability without obvious phase separation during thousands of charge/discharge and repeated bending cycles. This novel strategy by interface engineering of electrolyte to suppress the self-discharge behavior of supercapacitors is very meaningful to promote their practical applications.
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http://dx.doi.org/10.1002/smll.202102054DOI Listing
July 2021

Cell landscape atlas for patients with chronic thromboembolic pulmonary hypertension after pulmonary endarterectomy constructed using single-cell RNA sequencing.

Aging (Albany NY) 2021 06 21;13(12):16485-16499. Epub 2021 Jun 21.

Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Institute of Respiratory Medicine, Beijing 100020, China.

This study aimed to construct an atlas of the cell landscape and comprehensively characterize the cellular repertoire of the pulmonary endarterectomized tissues of patients with chronic thromboembolic pulmonary hypertension (CTEPH). Five pulmonary endarterectomized tissues were collected. 10× Genomics single-cell RNA sequencing was performed, followed by the identification of cluster marker genes and cell types. Gene Ontology (GO) enrichment analysis was conducted. Seventeen cell clusters were characterized, corresponding to 10,518 marker genes, and then classified into eight cell types, including fibroblast/smooth muscle cell, endothelial cell, T cell/NK cell, macrophage, mast cell, cysteine rich secretory protein LCCL domain containing 2 (CRISPLD2)+ cell, cancer stem cell, and undefined. The specific marker genes of fibroblast/smooth muscle cell, endothelial cell, T cell/NK cell, macrophage, mast cell, and cancer stem cell were significantly enriched for multiple functions associated with muscle cell migration, endothelial cell migration, T cell activation, neutrophil activation, erythrocyte homeostasis, and tissue remodeling, respectively. No functions were significantly enriched for the marker gene of CRISPLD2+ cell. Our study, for the first time, provides an atlas of the cell landscape of the pulmonary endarterectomized tissues of CTEPH patients at single-cell resolution, which may serve as a valuable resource for further elucidation of disease pathophysiology.
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http://dx.doi.org/10.18632/aging.203168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266372PMC
June 2021

[Clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation: a multicenter retrospective analysis].

Zhongguo Dang Dai Er Ke Za Zhi 2021 Jun;23(6):593-598

Department of Neonatology, Women's Hospital of Nanjing Medical University/Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, China.

Objective: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation.

Methods: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (=1 184), tracheal intubation (=166), and extensive cardiopulmonary resuscitation (ECPR; =116). The three groups were compared in terms of general information and clinical outcomes.

Results: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid ( < 0.05). As the intensity of resuscitation increased, the Apgar scores at 1 minute and 5 minutes gradually decreased ( < 0.05), and the proportion of infants with Apgar scores of 0 to 3 at 1 minute and 5 minutes gradually increased ( < 0.05). Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly higher mortality rate and incidence rates of moderate-severe bronchopulmonary dysplasia and serious complications ( < 0.05). The incidence rates of grade Ⅲ-Ⅳ intracranial hemorrhage and retinopathy of prematurity (stage Ⅲ or above) in the tracheal intubation group were significantly higher than those in the non-tracheal intubation group ( < 0.05).

Conclusions: For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214002PMC
June 2021

Searching Multi-Rate and Multi-Modal Temporal Enhanced Networks for Gesture Recognition.

IEEE Trans Image Process 2021 18;30:5626-5640. Epub 2021 Jun 18.

Gesture recognition has attracted considerable attention owing to its great potential in applications. Although the great progress has been made recently in multi-modal learning methods, existing methods still lack effective integration to fully explore synergies among spatio-temporal modalities effectively for gesture recognition. The problems are partially due to the fact that the existing manually designed network architectures have low efficiency in the joint learning of multi-modalities. In this paper, we propose the first neural architecture search (NAS)-based method for RGB-D gesture recognition. The proposed method includes two key components: 1) enhanced temporal representation via the proposed 3D Central Difference Convolution (3D-CDC) family, which is able to capture rich temporal context via aggregating temporal difference information; and 2) optimized backbones for multi-sampling-rate branches and lateral connections among varied modalities. The resultant multi-modal multi-rate network provides a new perspective to understand the relationship between RGB and depth modalities and their temporal dynamics. Comprehensive experiments are performed on three benchmark datasets (IsoGD, NvGesture, and EgoGesture), demonstrating the state-of-the-art performance in both single- and multi-modality settings. The code is available at https://github.com/ZitongYu/3DCDC-NAS.
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http://dx.doi.org/10.1109/TIP.2021.3087348DOI Listing
June 2021

Decreased Low-Density Lipoprotein Cholesterol Level Indicates Poor Prognosis of Severe and Critical COVID-19 Patients: A Retrospective, Single-Center Study.

Front Med (Lausanne) 2021 26;8:585851. Epub 2021 May 26.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Coronavirus disease 2019 (COVID-19) has become a global public health crisis. Reduced low-density lipoprotein cholesterol (LDL-C) levels were observed in COVID-19 patients. The present study aimed to explore the relationship between LDL-C levels and the prognosis of severe and critical COVID-19 patients. A total of 211 severe and critical COVID-19 patients were enrolled and divided into four groups according to the LDL-C levels, including 53 patients in Group A (LDL-C ≥ 2.71 mmol/L), 53 patients in Group B (2.28 ≤ LDL-C < 2.71 mmol/L), 53 patients in Group C (1.83 ≤ LDL-C < 2.28 mmol/L) and 52 patients in Group D (LDL-C < 1.83 mmol/L). LDL-C levels were lower in critically ill patients than in severe patients. The main symptoms before admission, characteristics on admission and comorbidities of enrolled patients did not differ among the four groups. Compared with patients with high LDL-C levels, patients with low LDL-C levels were more likely to have immune and inflammation dysfunction, renal dysfunction, liver dysfunction and cardiac dysfunction on admission. The proportions of patients with shock and acute cardiac injury, of those admitted to intensive care unit (ICU) and of those treated with mechanical ventilation were inversely related to LDL-C level. The mortality of COVID-19 patients increased with LDL-C reduction. Serum LDL-C levels of COVID-19 patients was negatively correlated with CRP level, but positively correlated with lymphocyte count, as shown by Pearson correlation analysis. Proportional hazard models showed that low LDL-C levels were associated with increased risk of hospitalization death, cardiac injury and admission to the ICU. Taken together, these results suggest that decreased LDL-C levels indicate poor prognosis of severe and critical COVID-19 patients.
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http://dx.doi.org/10.3389/fmed.2021.585851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187559PMC
May 2021

Multilevel resistive random access memory achieved by MoO/Hf/MoOstack and its application in tunable high-pass filter.

Nanotechnology 2021 Jun 29;32(38). Epub 2021 Jun 29.

School of Microelectronics, Faculty of Electronics and Information Engineering, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.

In this work, the multilevel resistive random access memories (RRAMs) have been achieved by using the structure of Pt/MoO/Hf/MoO/Pt with four stable resistance states. The devices show good retention property of each state (>10s) and large memory window (>10). The simulation and experimental study reveal that the resistive switching mechanism is ascribed to combination of the conductive filament in the stack of MoO/Hf next to the top electrode and redox reaction at the interface of Hf/MoOnext to bottom electrode. The fitting results of current-voltage characteristics under low sweep voltage indicate that the conduction of HRSs is dominated by the Poole-Frenkel emission and that of LRS is governed by the Ohmic conduction. Based on the RRAM, the tunable high-pass filter (HPF) with configurable filtering characteristics has been realized. The gain-frequency characteristics of the programmable HPF show that the filter has high resolution and wide programming range, demonstrating the viability of the multilevel RRAMs for future spiking neural network and shrinking the programmable filters with low power consumption.
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http://dx.doi.org/10.1088/1361-6528/ac0ac4DOI Listing
June 2021

Monte Carlo determination of dose coefficients at different developmental stages of zebrafish (Danio rerio) in experimental condition.

J Environ Radioact 2021 Jun 8;237:106667. Epub 2021 Jun 8.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, China; Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions. Electronic address:

The release of liquid effluent of nuclear power into aquatic system increases with the rapid development of nuclear facilities in coastal and inland regions. Aquatic model animals are very important for the study of the radiation hazards to non-human biota in water environment and its extrapolation of dose-effect relationship to human models. However, the study of the radiation dose rate calculation model of the aquatic animal zebrafish is still on the homogeneous isotropic model used for the protection of the environment. A series of zebrafish models (including adults, larvae and embryos, named zebrafish-family: ZF-family) with multiple internal organs are established in this study to investigate the mechanism of radiation damage effect in order to protect non-human species. The internal and external dose coefficients (DCs) of the whole body, heart and gonads of zebrafishes are calculated in water environment with the combination of the real experimental culture condition, using Monte Carlo application package GATE (Geant4 Application for Emission Tomography) and eight nuclides, i.e., H, C, Sr, Co, Ag, Cs, Cs, I, which are commonly found in the liquid effluent of nuclear power plants, as the source items, The results show that the level of nuclide γ energy determines the external DCs (DC), and Sr plays the most important role in internal DCs (DC). The comparison between the external DCs of the heart and gonad and that of the whole body shows that DCs (DC) of heart and gonad for females are 80% and 43% lower than that of whole body, respectively, while for males, the DCs (DC) of heart is 44% lower than that of the whole body, and DCs (DC) of gonad is slightly higher than that of the whole body for most nuclides (up to 25%).The dose of internal radiation makes greater contribution than that of external radiation to pure beta emitter (H, C, Sr). This internal DCs of ZF-family model with complex internal structure turns out to demonstrate more sensitive DCs change trend and higher calculation values compared with the internal DCs of the simple ellipsoid model. In this model, the photon emitter with strong penetrating power has higher internal DCs, while the low-energy pure beta nuclide does not alter much. In conclusion, it is vital to carry out refined systematic modeling for model organisms, and the determination of DCs of model organs can promote the evaluation of the radiation effects on non-human species.
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http://dx.doi.org/10.1016/j.jenvrad.2021.106667DOI Listing
June 2021

[Retracted] MicroRNA-124 suppresses the migration and invasion of osteosarcoma cells via targeting ROR2-mediated non-canonical Wnt signaling.

Oncol Rep 2021 Aug 10;46(2). Epub 2021 Jun 10.

Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell Transwell assay data in the article (featured in Figs. 2C and 5B) were strikingly similar to data appearing in different form in other articles by different authors, which were either already under consideration for publication or had already been published elsewhere at the time of the present article's submission. Owing to the fact that the contentious data in the above article were either already under consideration for publication, or had already been published elsewhere, prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in 34: 2195‑2201, 2015; DOI: 10.3892/or.2015.4186].
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http://dx.doi.org/10.3892/or.2021.8107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201471PMC
August 2021

[Retracted] MicroRNA-205 acts as a tumor suppressor in osteosarcoma via targeting RUNX2.

Oncol Rep 2021 Aug 10;46(2). Epub 2021 Jun 10.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell Transwell assay data in the article (featured in Fig. 3C and D) were strikingly similar to data that appearing in different form in other articles by different authors at different research institutions, which were already under consideration for publication or had already been published elsewhere at the time of the present article's submission. Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in 35: 3275-3284, 2016; DOI: 10.3892/or.2016.4700].
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http://dx.doi.org/10.3892/or.2021.8106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201454PMC
August 2021

Aging- and Tumor-Mediated Increase in CD8CD28 T Cells Might Impose a Strong Barrier to Success of Immunotherapy in Glioblastoma.

Immunohorizons 2021 Jun 8;5(6):395-409. Epub 2021 Jun 8.

Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI; and

Clinical use of various forms of immunotherapeutic drugs in glioblastoma (GBM), has highlighted severe T cell dysfunction such as exhaustion in GBM patients. However, reversing T cell exhaustion using immune checkpoint inhibitors in GBM clinical trials has not shown significant overall survival benefit. Phenotypically, CD8 T cells with downregulated CD28 coreceptors, low CD27 expression, increased CD57 expression, and telomere shortening are classified as senescent T cells. These senescent T cells are normally seen as part of aging and also in many forms of solid cancers. Absence of CD28 on T cells leads to several functional irregularities including reduced TCR diversity, incomplete activation of T cells, and defects in Ag-induced proliferation. In the context of GBM, presence and/or function of these CD8CD28 T cells is unknown. In this clinical correlative study, we investigated the effect of aging as well as tumor microenvironment on CD8 T cell phenotype as an indicator of its function in GBM patients. We systematically analyzed and describe a large population of CD8CD28 T cells in both the blood and tumor-infiltrating lymphocytes of GBM patients. We found that phenotypically these CD8CD28 T cells represent a distinct population compared with exhausted T cells. Comparative transcriptomic and pathway analysis of CD8CD28 T cell populations in GBM patients revealed that tumor microenvironment might be influencing several immune related pathways and thus further exaggerating the age associated immune dysfunction in this patient population.
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http://dx.doi.org/10.4049/immunohorizons.2100008DOI Listing
June 2021

LncRNA HBL1 is required for genome-wide PRC2 occupancy and function in cardiogenesis from human pluripotent stem cells.

Development 2021 Jul 28;148(13). Epub 2021 Jun 28.

Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Polycomb repressive complex 2 (PRC2) deposits H3K27me3 on chromatin to silence transcription. PRC2 broadly interacts with RNAs. Currently, the role of the RNA-PRC2 interaction in human cardiogenesis remains elusive. Here, we found that human-specific heart brake lncRNA 1 (HBL1) interacted with two PRC2 subunits, JARID2 and EED, in human pluripotent stem cells (hPSCs). Loss of JARID2, EED or HBL1 significantly enhanced cardiac differentiation from hPSCs. HBL1 depletion disrupted genome-wide PRC2 occupancy and H3K27me3 chromatin modification on essential cardiogenic genes, and broadly enhanced cardiogenic gene transcription in undifferentiated hPSCs and later-on differentiation. In addition, ChIP-seq revealed reduced EED occupancy on 62 overlapped cardiogenic genes in HBL1-/- and JARID2-/- hPSCs, indicating that the epigenetic state of cardiogenic genes was determined by HBL1 and JARID2 at pluripotency stage. Furthermore, after cardiac development occurs, the cytosolic and nuclear fractions of HBL1 could crosstalk via a conserved 'microRNA-1-JARID2' axis to modulate cardiogenic gene transcription. Overall, our findings delineate the indispensable role of HBL1 in guiding PRC2 function during early human cardiogenesis, and expand the mechanistic scope of lncRNA(s) that cytosolic and nuclear portions of HBL1 could coordinate to orchestrate human cardiogenesis.
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http://dx.doi.org/10.1242/dev.199628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276986PMC
July 2021

Genome wide DNA methylation landscape reveals glioblastoma's influence on epigenetic changes in tumor infiltrating CD4+ T cells.

Oncotarget 2021 May 11;12(10):967-981. Epub 2021 May 11.

Department of Neurological Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.

CD4+ helper T (Th) cells play a critical role in shaping anti-tumor immunity by virtue of their ability to differentiate into multiple lineages in response to environmental cues. Various CD4+ lineages can orchestrate a broad range of effector activities during the initiation, expansion, and memory phase of endogenous anti-tumor immune response. In this clinical corelative study, we found that Glioblastoma (GBM) induces multi- and mixed-lineage immune response in the tumor microenvironment. Whole-genome bisulfite sequencing of tumor infiltrating and blood CD4+ T-cell from GBM patients showed 13571 differentially methylated regions and a distinct methylation pattern of methylation of tumor infiltrating CD4+ T-cells with significant inter-patient variability. The methylation changes also resulted in transcriptomic changes with 341 differentially expressed genes in CD4+ tumor infiltrating T-cells compared to blood. Analysis of specific genes involved in CD4+ differentiation and function revealed differential methylation status of TBX21, GATA3, RORC, FOXP3, IL10 and IFNG in tumor CD4+ T-cells. Analysis of lineage specific genes revealed differential methylation and gene expression in tumor CD4+ T-cells. Interestingly, we observed dysregulation of several ligands of T cell function genes in GBM tissue corresponding to the T-cell receptors that were dysregulated in tumor infiltrating CD4+ T-cells. Our results suggest that GBM might induce epigenetic alterations in tumor infiltrating CD4+ T-cells there by influencing anti-tumor immune response by manipulating differentiation and function of tumor infiltrating CD4+ T-cells. Thus, further research is warranted to understand the role of tumor induced epigenetic modification of tumor infiltrating T-cells to develop effective anti-GBM immunotherapy.
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http://dx.doi.org/10.18632/oncotarget.27955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121608PMC
May 2021

Trends in risk stratification, in-hospital management and mortality of patients with acute pulmonary embolism: an analysis from China pUlmonary thromboembolism REgistry Study (CURES).

Eur Respir J 2021 May 13. Epub 2021 May 13.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, P. R. China

Background: Similar trends of management and in-hospital mortality of acute pulmonary embolism (PE) have been reported in European and American populations. However, these tendencies were not clear in Asian countries.

Objectives: We retrospectively analyzed the trends of risk stratification, management and in-hospital mortality for patients with acute PE through a multicenter registry in China (CURES).

Methods: Adult patients with acute symptomatic PE were included between 2009 and 2015. Trends in disease diagnosis, treatment and death in hospital were fully analyzed. Risk stratification was retrospectively classified by hemodynamical status and the simplified Pulmonary Embolism Severity Index (sPESI) score according to the 2014 European Society of Cardiology/European Respiratory Society guidelines.

Results: Among overall 7438 patients, the proportions with high (hemodynamically instability), intermediate (sPESI≥1) and low (sPESI=0) risk were 4.2%, 67.1% and 28.7%, respectively. was the widely employed diagnostic approach (87.6%) and anticoagulation was the frequently adopted initial therapy (83.7%). Between 2009 and 2015, a significant decline was observed for all-cause mortality (from 3.1% to 1.3%, adjusted =0.0003), with a concomitant reduction in use of initial systemic thrombolysis (from 14.8% to 5.0%, <0.0001). The common predictors for all-cause mortality shared by hemodynamically stable and unstable patients were co-existing cancer, older age, and impaired renal function.

Conclusions: The considerable reduction of mortality over years was accompanied by changes of initial treatment. These findings highlight the importance of risk stratification-guided management throughout the nation.
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http://dx.doi.org/10.1183/13993003.02963-2020DOI Listing
May 2021

Fe-Doped Graphitic Carbon Nitride for Methylene Blue Degradation with Visible-Light.

J Nanosci Nanotechnol 2021 11;21(11):5698-5706

College of Environment and Safety Engineering, Qingdao University of Science and Technology Qingdao 266042, China.

In the present work, degradation of methylene blue (MB) dye in aqueous solution through H₂O ₂and iron doped g-C₃N₄ (Fe-g-C₃N₄) was studied. The hybrid was fabricated by thermal polymerization with iron (III) nitrate nonahydrate and melamine, and it was characterized by X-ray diffraction, Fourier transform infrared, UV-Vis diffuse reflectance spectrum, X-ray photoelectron spectroscopy, transmission electron microscope and Brunner-Emmet-Teller. The various experimental conditions such as doping amount, a dose of the sample, solution pH, the addition of H₂O₂, and concentration of MB on the degradation of MB dye were optimized. The maximum extent of degradation of methylene blue was obtained at pH 5, doping amount of 2.7 wt% and dose of 0.07 g. The molar ratio of Fe:H₂O₂ is 1:1000 showed 99% of MB (30 mg/L) decolorization over 60 min. The hybrid showed good stability and recyclability after three cycles of use. Photo-Fenton reaction exhibited a higher synergetic effect than the combination of Fenton and photocatalytic process.
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http://dx.doi.org/10.1166/jnn.2021.19487DOI Listing
November 2021

Identification of a New DNA Aptamer by Tissue-SELEX for Cancer Recognition and Imaging.

Anal Chem 2021 05 7;93(19):7369-7377. Epub 2021 May 7.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecule Engineering of Hunan Province, Hunan University, Changsha 410082, China.

Cancer has become one of the most common diseases with high mortality in humans. Early and accurate diagnosis of cancer is of great significance to enhance the survival rate of patients. Therefore, effective molecular ligands capable of selectively recognizing cancer are urgently needed. In this work, we identified a new DNA aptamer named SW1 by tissue-based systematic evolution of ligands by exponential enrichment (tissue-SELEX), in which cancerous liver tissue sections were used as the positive control and adjacent normal liver tissue sections were used as the negative control. Taking immobilized liver cancer SMMC-7721 cells as the research object, aptamer SW1 exhibited excellent affinity with a value of 123.62 ± 17.53 nM, and its binding target was preliminarily determined as a non-nucleic acid substance in the nucleus. Moreover, tissue imaging results showed that SW1 explicitly recognized cancerous liver tissues with a high detection rate of 72.7% but displayed a low detection rate to adjacent normal tissues. In addition to liver cancer cells and tissues, aptamer SW1 has been demonstrated to recognize various other types of cancer cells and tissues. Furthermore, SW1-A, an optimized aptamer of SW1, maintained its excellent affinity toward liver cancer cells and tissues. Collectively, these results indicate that SW1 possesses great potential for use as an effective molecular probe for clinical diagnosis of cancer.
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http://dx.doi.org/10.1021/acs.analchem.1c01445DOI Listing
May 2021

BATF Regulates T Regulatory Cell Functional Specification and Fitness of Triglyceride Metabolism in Restraining Allergic Responses.

J Immunol 2021 May 19;206(9):2088-2100. Epub 2021 Apr 19.

Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN;

Preserving appropriate function and metabolism in regulatory T (Treg) cells is crucial for controlling immune tolerance and inflammatory responses. Yet how Treg cells coordinate cellular metabolic programs to support their functional specification remains elusive. In this study, we report that BATF couples the T2-suppressive function and triglyceride (TG) metabolism in Treg cells for controlling allergic airway inflammation and IgE responses. Mice with Treg-specific ablation of BATF developed an inflammatory disorder characterized by T2-type dominant responses and were predisposed to house dust mite-induced airway inflammation. Loss of BATF enabled Treg cells to acquire T2 cell-like characteristics. Moreover, BATF-deficient Treg cells displayed elevated levels of cellular TGs, and repressing or elevating TGs, respectively, restored or exacerbated their defects. Mechanistically, TCR/CD28 costimulation enhanced expression and function of BATF, which sustained IRF4 activity to preserve Treg cell functionality. Thus, our studies reveal that BATF links Treg cell functional specification and fitness of cellular TGs to control allergic responses, and suggest that therapeutic targeting of TG metabolism could be used for the treatment of allergic disease.
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http://dx.doi.org/10.4049/jimmunol.2001184DOI Listing
May 2021

Circulating IL-37 levels are elevated in patients with hypertension.

Exp Ther Med 2021 Jun 26;21(6):558. Epub 2021 Mar 26.

Department of Cardiology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China.

Interleukin-37 (IL-37) has been reported to be closely linked to vascular diseases, including atherosclerosis and aortic calcification. The present study aimed to assess the expression levels of IL-37 in patients with hypertension. Blood samples were collected from control subjects (n=20) and patients with hypertension (n=45). Subsequently, macrophages, lymphocytes and dendritic cells were individually isolated and the mRNA expression of IL-37 was measured. In addition, the circulating IL-37 levels in control subjects (n=30) and patients with hypertension (n=334) were assessed. Furthermore, all patients who were subjected to detection of circulating IL-37 underwent ambulatory blood pressure monitoring. The results suggested that the mRNA levels of IL-37 in macrophages, but not in lymphocytes and dendritic cells, isolated from patients with hypertension were markedly elevated compared with those in cells isolated from control subjects. Circulating IL-37 levels were increased in patients with hypertension compared with those in control subjects and positively correlated with systolic and diastolic blood pressure in patients with hypertension. No differences were observed between patients with dipper hypertension and patients with non-dipper hypertension. In addition, patients with hypertension with a smoking habit, type 2 diabetes mellitus and carotid atherosclerotic plaque (CAP) exhibited higher IL-37 levels. IL-37 levels were positively correlated with creatinine, C-reactive protein and homocysteine levels. Furthermore, the results of a linear regression analysis suggested that IL-37 levels were independently associated with the presence of CAP. In conclusion, IL-37 levels are increased in patients with hypertension and may be associated with the onset of CAP.
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http://dx.doi.org/10.3892/etm.2021.9990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027753PMC
June 2021

Maresin 1 alleviates the inflammatory response, reduces oxidative stress and protects against cardiac injury in LPS-induced mice.

Life Sci 2021 Jul 31;277:119467. Epub 2021 Mar 31.

Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan 430060, China. Electronic address:

Background: Maresin 1 (MaR1) is a pro-resolving lipid mediator that has been reported to have strong regulatory effects on oxidative stress and inflammation. This study aimed to determine the effect of MaR1 on lipopolysaccharide (LPS)-induced sepsis-related cardiac injury and explore its possible mechanisms.

Methods: Mice were administered MaR1 or PBS and then treated with LPS or saline for 6 h. Then, cardiac function, cardiac injury markers, cardiac macrophage differentiation, oxidative stress and myocardial cell apoptosis in each group were measured.

Results: MaR1 treatment significantly decreased the serum levels of lactate dehydrogenase (LDH) and kinase isoenzyme (CK-MB) and improved cardiac function in LPS-induced mice. Treatment with MaR1 also inhibited LPS-induced M1 macrophage differentiation and reduced M1 macrophage-related cytokine secretion while promoting M2 macrophage differentiation and increasing M2 macrophage-related inflammatory mediator expression. In addition, MaR1 decreased serum malondialdehyde (MDA) levels and increased serum levels of superoxide dismutase (SOD) and glutathione (GSH), as well as cardiac expression of nuclear factor erythroid-2 related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1), in LPS-induced mice. Furthermore, fewer TUNEL-positive cells were observed in the LPS + MaR1 group than in the LPS group.

Conclusions: Our experimental results show that MaR1 alleviates cardiac injury and protects against cardiac dysfunction and may be beneficial in reducing sepsis-induced cardiac injury.
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http://dx.doi.org/10.1016/j.lfs.2021.119467DOI Listing
July 2021

Transcriptome Landscape of Epithelial to Mesenchymal Transition of Human Stem Cell-Derived RPE.

Invest Ophthalmol Vis Sci 2021 Apr;62(4)

Department of Ophthalmology, Stem Cell Ocular Regenerative Medicine Center, Wilmer Eye Institute, The Johns Hopkins University School of Medicine Baltimore, Maryland, United States.

Purpose: RPE injury often induces epithelial to mesenchymal transition (EMT). Although RPE-EMT has been implicated in a variety of retinal diseases, including proliferative vitroretinopathy, neovascular and atrophic AMD, and diabetic retinopathy, it is not well-understood at the molecular level. To contribute to our understanding of EMT in human RPE, we performed a time-course transcriptomic analysis of human stem cell-derived RPE (hRPE) monolayers induced to undergo EMT using 2 independent, yet complementary, model systems.

Methods: EMT of human stem cell-derived RPE monolayers was induced by either enzymatic dissociation or modulation of TGF-β signaling. Transcriptomic analysis of cells at different stages of EMT was performed by RNA-sequencing, and select findings were confirmed by reverse transcription quantitative PCR and immunostaining. An ingenuity pathway analysis (IPA) was performed to identify signaling pathways and regulatory networks associated with EMT.

Results: Proteocollagenolytic enzymatic dissociation and cotreatment with TGF-β and TNF-α both induce EMT in human stem cell-derived RPE monolayers, leading to an increased expression of mesenchymal factors and a decreased expression of RPE differentiation-associated factors. Ingenuity pathway analysis identified the upstream regulators of the RPE-EMT regulatory networks and identified master switches and nodes during RPE-EMT. Of particular interest was the identification of widespread dysregulation of axon guidance molecules during RPE-EMT progression.

Conclusions: The temporal transcriptome profiles described here provide a comprehensive resource of the dynamic signaling events and the associated biological pathways that underlie RPE-EMT onset. The pathways defined by these studies may help to identify targets for the development of novel therapeutic targets for the treatment of retinal disease.
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http://dx.doi.org/10.1167/iovs.62.4.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024778PMC
April 2021

A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells.

Cell Rep Med 2021 Mar 16;2(3):100219. Epub 2021 Mar 16.

Department of Surgery, Indiana University of School of Medicine, Indianapolis, IN 46202, USA.

Single-cell RNA sequencing (scRNA-seq) is an evolving technology used to elucidate the cellular architecture of adult organs. Previous scRNA-seq on breast tissue utilized reduction mammoplasty samples, which are often histologically abnormal. We report a rapid tissue collection/processing protocol to perform scRNA-seq of breast biopsies of healthy women and identify 23 breast epithelial cell clusters. Putative cell-of-origin signatures derived from these clusters are applied to analyze transcriptomes of ~3,000 breast cancers. Gene signatures derived from mature luminal cell clusters are enriched in ~68% of breast cancers, whereas a signature from a luminal progenitor cluster is enriched in ~20% of breast cancers. Overexpression of luminal progenitor cluster-derived signatures in HER2+, but not in other subtypes, is associated with unfavorable outcome. We identify TBX3 and PDK4 as genes co-expressed with estrogen receptor (ER) in the normal breasts, and their expression analyses in >550 breast cancers enable prognostically relevant subclassification of ER+ breast cancers.
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http://dx.doi.org/10.1016/j.xcrm.2021.100219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974552PMC
March 2021

Recordings from neuron-HEK cell cocultures reveal the determinants of miniature excitatory postsynaptic currents.

J Gen Physiol 2021 May;153(5)

Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Spontaneous exocytosis of single synaptic vesicles generates miniature synaptic currents, which provide a window into the dynamic control of synaptic transmission. To resolve the impact of different factors on the dynamics and variability of synaptic transmission, we recorded miniature excitatory postsynaptic currents (mEPSCs) from cocultures of mouse hippocampal neurons with HEK cells expressing the postsynaptic proteins GluA2, neuroligin 1, PSD-95, and stargazin. Synapses between neurons and these heterologous cells have a molecularly defined postsynaptic apparatus, while the compact morphology of HEK cells eliminates the distorting effect of dendritic filtering. HEK cells in coculture produced mEPSCs with a higher frequency, larger amplitude, and more rapid rise and decay than neurons from the same culture. However, mEPSC area indicated that nerve terminals in synapses with both neurons and HEK cells release similar populations of vesicles. Modulation by the glutamate receptor ligand aniracetam revealed receptor contributions to mEPSC shape. Dendritic cable effects account for the slower mEPSC rise in neurons, whereas the slower decay also depends on other factors. Lastly, expression of synaptobrevin transmembrane domain mutants in neurons slowed the rise of HEK cell mEPSCs, thus revealing the impact of synaptic fusion pores. In summary, we show that cocultures of neurons with heterologous cells provide a geometrically simplified and molecularly defined system to investigate the time course of synaptic transmission and to resolve the contribution of vesicles, fusion pores, dendrites, and receptors to this process.
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http://dx.doi.org/10.1085/jgp.202012849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992392PMC
May 2021

The Association between Obesity and Severity in Patients with Coronavirus Disease 2019: a Retrospective, Single-center Study, Wuhan.

Int J Med Sci 2021 18;18(8):1768-1777. Epub 2021 Feb 18.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.

In other respiratory infectious diseases, obesity may be associated with a poor outcome. For coronavirus disease 2019 (COVID-19), the association between obesity and severity or prognosis requires further analysis. This was a retrospective, single-center study. Hospitalized patients were recruited in Renmin Hospital of Wuhan University from January 2, 2020 to February 20, 2020. The data of body mass index (BMI) was obtained from follow-up of surviving patients. According to BMI, normal weight was defined as 18.5-23.9 kg/m, overweight as 24.0-27.9 kg/m and obesity as > 28.0 kg/m. A total of 463 patients were enrolled, of which 242 (52.3%) patients were in the normal weight group; 179 (38.7%) were in the overweight group; and 42 (9.1%) were in the obesity group. Compared to the normal group, obese patients were more likely to have a higher heart rate; lower finger oxygen saturation; higher levels of white blood cells, neutrophil counts, basophil counts, intravenous glucose, triacylglycerol, uric acid, alanine aminotransferase, creatine kinase-MB, CD19+ cell counts and percentage; and lower levels of monocyte percentage, high density lipoprotein and CD3+ cell percentage. In addition, the proportions of hypertension (21.5% vs. 42.6%) and severe+critical illness (47.8 vs. 81.0 %) were significantly higher in the obesity group than those in normal group. However, no significant differences were observed between the normal and obesity groups in critical illness, organ damage and defined endpoint (mechanical ventilation or intensive care unit). Multiple logistic regression showed that obesity increased the risk of developing severe+critical illness (Odd ratio 3.586, 95% CI 1.550-8.298, P=0.003) in patients with COVID-19, and did not affect the risk of critical illness, organ damage and endpoints. Overweight did not affect the risk of severity, organ damage or endpoint in patients with COVID-19. Obesity may be a risk factor for developing severity in patients with COVID-19.
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http://dx.doi.org/10.7150/ijms.54655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976577PMC
March 2021

Added Value of Blood Cells in Thrombin Generation Testing.

Thromb Haemost 2021 Mar 19. Epub 2021 Mar 19.

Synapse Research Institute, Maastricht, The Netherlands.

The capacity of blood to form thrombin is a critical determinant of coagulability. Plasma thrombin generation (TG), a test that probes the capacity of plasma to form thrombin, has improved our knowledge of the coagulation system and shows promising utility in coagulation management. Although plasma TG gives comprehensive insights into the function of pro- and anticoagulation drivers, it does not measure the role of blood cells in TG. In this literature review, we discuss currently available continuous TG tests that can reflect the involvement of blood cells in coagulation, in particular the fluorogenic assays that allow continuous measurement in platelet-rich plasma and whole blood. We also provide an overview about the influence of blood cells on blood coagulation, with emphasis on the direct influence of blood cells on TG. Platelets accelerate the initiation and velocity of TG by phosphatidylserine exposure, granule content release and surface receptor interaction with coagulation proteins. Erythrocytes are also major providers of phosphatidylserine, and erythrocyte membranes trigger contact activation. Furthermore, leukocytes and cancer cells may be important players in cell-mediated coagulation because, under certain conditions, they express tissue factor, release procoagulant components and can induce platelet activation. We argue that testing TG in the presence of blood cells may be useful to distinguish blood cell-related coagulation disorders. However, it should also be noted that these blood cell-dependent TG assays are not clinically validated. Further standardization and validation studies are needed to explore their clinical usefulness.
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http://dx.doi.org/10.1055/a-1450-8300DOI Listing
March 2021

Thermal treatment decreases resistance to osimertinib in non-small cell lung cancer through the EGFR/PI3K/AKT pathway.

Neoplasma 2021 May 17;68(3):535-545. Epub 2021 Mar 17.

Department of Thoracic Surgery, The Shenzhen People's Hospital, The Second Clinical Medicine College of Jinan University, Shenzhen, Guangdong, China.

Osimertinib (OSI) resistance commonly occurs during the treatment of non-small-cell lung cancer (NSCLC). This study aims to investigate whether the thermal effects of radiofrequency ablation (RFA) can increase the sensitivity of OSI-resistant NSCLC to OSI treatment and whether OSI effectively inhibits the recurrence of OSI-resistant NSCLC following RFA treatment and improve survival of NSCLC patients. In vitro, OSI-resistant NCI-H1975 (NCI-H1975/OSIR) cells and thermotolerant NCI-H1975/OSIR (NCI-H1975/OSIR-a-h) cells were established using human NSCLC cell line NCI-H1975. Cell viability, apoptosis, sensitivity to OSI, threonine-methionine amino acid substitution at position 790 (T790M) mutation levels, and protein expression of epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), hypoxia-inducible factor-1 alpha (HIF-1a) were detected using different methods. In vivo, a nude mouse model of metastatic human lung cancer was developed and subjected to RFA treatment. The tumor growth, apoptosis, sensitivity to OSI, expression of EGFR/PI3K/AKT/HIF-1a, and CD34 levels were detected in the micrometastases of the transition zone (TZ) around the central ablation zone, and the reference zone (RZ) far from central ablation zone. NCI-H1975/OSIR and thermotolerant NCI-H1975/OSIR cell models were successfully established. Thermotolerant NCI-H1975/OSIR cells show higher sensitivity to OSI than NCI-H1975/OSIR cells and NCI-H1975 cells. OSI treatment can inhibit the EGFR/PI3K/AKT pathway and induce apoptosis in both NCI-H1975 cells and thermotolerant NCI-H1975/OSIR cells, but not in NCI-H1975/OSIR cells. In vivo, RFA treatment increases sensitivity to OSI in NCI-H1975/OSIR cell micrometastases in the TZ but not in the RZ. OSI intervention effectively inhibits the over-proliferation of micrometastases and activation of the EGFR/PI3K/AKT pathway, and induces apoptosis of micrometastases in the TZ, but shows little effects on the micrometastases in the RZ. The thermal effects can increase the sensitivity of OSI-resistant NSCLC cells to OSI through the EGFR/PI3K/AKT/HIF-1a signaling pathway, indicating that RFA combined with OSI might be a clinically effective and comprehensive therapy for the treatment of OSI-resistant NSCLC.
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http://dx.doi.org/10.4149/neo_2021_200506N489DOI Listing
May 2021

The role of interleukin-10 family members in cardiovascular diseases.

Int Immunopharmacol 2021 May 1;94:107475. Epub 2021 Mar 1.

The First Clinical College of Wuhan University, Wuhan, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China. Electronic address:

Interleukin (IL)-10 cytokine family members, including IL-10, IL-19, IL-20, IL-22, IL-24, IL-26 and the distantly related IL-28A, IL-28B, and IL-29, play critical roles in the regulation of inflammation. The occurrence and progression of cardiovascular diseases closely correlate with the regulation of inflammation, which may provide novel strategies for the treatment of cardiovascular diseases. In recent years, studies have focused on the association between the IL-10 cytokine family and the physiological and pathological progression of cardiovascular diseases. The aim of this review is to summarize relevant studies and clarify whether the IL-10 cytokine family contributes to the regulation of cardiovascular diseases.
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http://dx.doi.org/10.1016/j.intimp.2021.107475DOI Listing
May 2021
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