Publications by authors named "Honglei Liu"

127 Publications

The high prevalence of abnormal MRI findings in non-neuropsychiatric patients with persistently positive antiphospholipid antibodies.

Rheumatology (Oxford) 2021 Sep 24. Epub 2021 Sep 24.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objectives: Thrombosis occurring in the central nerve system is common in antiphospholipid syndrome (APS) patients, leading to neuropsychiatric symptoms. We investigated the prevalence of silent brain abnormalities on magnetic resonance imaging (MRI) in primary antiphospholipid syndrome (PAPS) patients and antiphospholipid antibodies (aPL) carriers and assessed the association between the vascular risk factors, aPL profile, clinical manifestations, and MRI abnormalities.

Methods: We consecutively included 44 PAPS patients, 24 aPL carriers and 23 healthy controls with comparable age and gender in a single-center, observational cross-sectional study. None of the patients had a history of stroke, TIA, migraine, dementia, epilepsy and bipolar disorders. On cerebral MRI, we assessed the imaging features and location of abnormality. Multivariate analysis was performed to identify the risk factors contributing to the MRI abnormalities.

Results: 38 (55.88%) patients persisted abnormal MRI findings, while only one healthy control showed some abnormalities in the MR findings. Lacunes were the most frequent MRI abnormality in aPL (+) group (31/68, 45.59%), which were followed by white matter hyperintensities (20/68, 29.41%). In all study population, age (OR = 1.086, p= 0.016) and LA positivity (OR = 5.191, p= 0.002) were the independent associated factors with the brain MRI abnormalities. When analyzed only in the aPL (+) group, age (OR = 1.116, p= 0.007), female gender (OR = 7.519, p= 0.025) and thrombocytopenia (OR = 8.336, p= 0.047) were the significant independent risk factors with abnormal MRI.

Conclusions: PAPS patients and aPL carriers showed a high prevalence of brain MRI abnormalities, indicating an increased cerebrovascular risk, which emphasized attention to silent cerebral lesions in persistently aPL positive patients.
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http://dx.doi.org/10.1093/rheumatology/keab649DOI Listing
September 2021

Plasma exchange therapy in refractory inflammatory myopathy with anti-signal recognition particle antibody: a case series.

Rheumatology (Oxford) 2021 Sep 11. Epub 2021 Sep 11.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objectives: To explore the efficacy of plasma exchange (PE) therapy in refractory idiopathic inflammatory myopathy (IIM) patients with positive anti-signal recognition particle (SRP) antibody.

Methods: Nine refractory IIM patients with positive anti-SRP antibody were enrolled, who received PE therapy at Ruijin Hospital from Octobor 2017 to December 2020. The clinical manifestations, laboratory tests, chest CT and lower extremity MRI images before and after PE therapy were compared. The treatment response was evaluated by the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria.

Results: 88.9% (8/9) subjects had achieved improvement by 3 weeks after PE therapy, with 55.6% (5/9) minimal improvement and 33.3% (3/9) moderate improvement. There were statistically significant improvements between baseline and after PE therapy at 3 weeks on the core set measures: physician global activity, patient global activity, Health Assessment Questionnaire (HAQ), manual muscle testing (MMT), extramuscular disease activity, and muscle enzymes activity including creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), except for alanine transaminase (ALT). Moreover, the chest CT showed regression of ground glass opacities and irregular linear opacities after PE therapy in four patients with interstitial lung disease. The MRI images of lower extremity in four patients showed reduction of muscle oedema after the therapy.

Conclusion: PE therapy is effective for refractory IIM patients with positive anti-SRP antibody. It should be considered as an alternative treatment for those patients who are resistant to the combined therapy of glucocorticoids and immunosuppressive agents.
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http://dx.doi.org/10.1093/rheumatology/keab629DOI Listing
September 2021

Urine Proteomics Differentiate Primary Thrombotic Antiphospholipid Syndrome From Obstetric Antiphospholipid Syndrome.

Front Immunol 2021 19;12:702425. Epub 2021 Aug 19.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Antiphospholipid syndrome (APS) is a multisystem disorder characterized by thrombosis and/or recurrent fetal loss. This clinical phenotype heterogeneity may result in differences in response to treatment and prognosis. In this study, we aimed to identify primary thrombotic APS (TAPS) from primary obstetric APS (OAPS) using urine proteomics as a non-invasive method. Only patients with primary APS were enrolled in this study from 2016 to 2018 at a single clinical center in Shanghai. Urine samples from 15 patients with TAPS, 9 patients with OAPS, and 15 healthy controls (HCs) were collected and analyzed using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis to identify differentially expressed proteins. Cluster analysis of urine proteomics identified differentiated proteins among the TAPS, OAPS, and HC groups. Urinary proteins were enriched in cytokine and cytokine receptor pathways. Representative secreted cytokines screened out (fold change >1.20, or <0.83, <0.05) in these differentiated proteins were measured by enzyme-linked immunosorbent assay in a validation cohort. The results showed that the levels of C-X-C motif chemokine ligand 12 (CXCL12) were higher in the urine of patients with TAPS than in those with OAPS (=0.035), while the levels of platelet-derived growth factor subunit B (PDGFB) were lower in patients with TAPS than in those with OAPS (=0.041). In addition, correlation analysis showed that CXCL12 levels were positively correlated with immunoglobulin G anti-β2-glycoprotein I antibody (=0.617, =0.016). Our results demonstrated that urinary CXCL12 and PDGFB might serve as potential non-invasive markers to differentiate primary TAPS from primary OAPS.
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http://dx.doi.org/10.3389/fimmu.2021.702425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416615PMC
August 2021

Transcriptome and Coexpression Network Analyses Reveal Hub Genes in Chinese Cabbage ( L. ssp. ) During Different Stages of Infection.

Front Plant Sci 2021 10;12:650252. Epub 2021 Aug 10.

Institute of Horticulture, Henan Academy of Agricultural Sciences, Graduate T&R Base of Zhengzhou University, Zhengzhou, China.

Clubroot, caused by the soil-borne protist , is one of the most destructive diseases of Chinese cabbage worldwide. However, the clubroot resistance mechanisms remain unclear. In this study, in both clubroot-resistant (DH40R) and clubroot-susceptible (DH199S) Chinese cabbage lines, the primary (root hair infection) and secondary (cortical infection) infection stages started 2 and 5 days after inoculation (dai), respectively. With the extension of the infection time, cortical infection was blocked and complete resistance was observed in DH40R, while disease scales of 1, 2, and 3 were observed at 8, 13, and 22 dai in DH199S. Transcriptome analysis at 0, 2, 5, 8, 13, and 22 dai identified 5,750 relative DEGs (rDEGs) between DH40R and DH199S. The results indicated that genes associated with auxin, PR, disease resistance proteins, oxidative stress, and and transcription factors were involved in clubroot resistance regulation. In addition, weighted gene coexpression network analysis (WGCNA) identified three of the modules whose functions were highly associated with clubroot-resistant, including ten hub genes related to clubroot resistance (, , , , , , two , , and ). These results provide valuable information for better understanding the molecular regulatory mechanism of Chinese cabbage clubroot resistance.
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http://dx.doi.org/10.3389/fpls.2021.650252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383047PMC
August 2021

Presence of polycyclic aromatic hydrocarbons among multi-media in a typical constructed wetland located in the coastal industrial zone, Tianjin, China: Occurrence characteristics, source apportionment and model simulation.

Sci Total Environ 2021 Aug 12;800:149601. Epub 2021 Aug 12.

Tianjin Academy of Environmental Sciences, Tianjin 300191, China.

In-depth understanding and accurately predicting the occurrence and fate of polycyclic aromatic hydrocarbons (PAHs) in constructed wetlands (CWs) is extremely crucial for optimizing the CWs construction and strengthening the risk control. However, few studies have focused on the PAHs among sediment-water-plant and model simulation in CWs. In this study, sediment, surface water and reed samples were gathered and analyzed from a typical CW. The concentrations of 16 PAHs (ΣPAHs) in sediments, surface water and reeds ranged from 620 to 4277 μg/kg, 114 to 443 ng/L and 74.5 to 362 μg/kg, respectively. The coefficients of variation (CV) were calculated as 0.796, 0.431 and 0.473 for the above three media respectively, indicating that the spatial distribution variation was medium intensity. The fugacity fraction (ff) suggested that sediments might act as the secondary release source of most PAHs. According to the diagnostic ratios and principal component analysis-multiple linear regression (PCA-MLR), PAHs in this CW mainly come from fossil fuels combustion and petroleum leakage. PAHs in sediments showed high ecological risk at water inlet and moderate risk at the other functional zones, while low risks for surface water at all functional zones. Although the human health risk assessment indicated relatively low cancer risk, the health risk still cannot be ignored with the continuous input and accumulation of exogenous PAHs. A mathematical model covering the hydraulics parameters and composition characteristics of the wetland was established, and its reliability was verified. The simulated results obtained by the established model were basically consistent with the measured values. In addition, the total remove efficiency of PAHs in surface water was 40.2%, which calculated by the simulated model. This work provides helpful insight into the comprehension of occurrence and fate of PAHs among multi-media in CWs.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149601DOI Listing
August 2021

Correspondence on "Update on the diagnosis and management of systemic lupus erythematosus" by Fanouriakis .

Ann Rheum Dis 2021 Aug 3. Epub 2021 Aug 3.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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http://dx.doi.org/10.1136/annrheumdis-2021-220897DOI Listing
August 2021

Study on the semi-supervised learning-based patient similarity from heterogeneous electronic medical records.

BMC Med Inform Decis Mak 2021 07 30;21(Suppl 2):58. Epub 2021 Jul 30.

School of Biomedical Engineering, Capital Medical University, No.10, Xitoutiao, You An Men, Fengtai District, Beijing, 100069, People's Republic of China.

Background: A new learning-based patient similarity measurement was proposed to measure patients' similarity for heterogeneous electronic medical records (EMRs) data.

Methods: We first calculated feature-level similarities according to the features' attributes. A domain expert provided patient similarity scores of 30 randomly selected patients. These similarity scores and feature-level similarities for 30 patients comprised the labeled sample set, which was used for the semi-supervised learning algorithm to learn the patient-level similarities for all patients. Then we used the k-nearest neighbor (kNN) classifier to predict four liver conditions. The predictive performances were compared in four different situations. We also compared the performances between personalized kNN models and other machine learning models. We assessed the predictive performances by the area under the receiver operating characteristic curve (AUC), F1-score, and cross-entropy (CE) loss.

Results: As the size of the random training samples increased, the kNN models using the learned patient similarity to select near neighbors consistently outperformed those using the Euclidean distance to select near neighbors (all P values < 0.001). The kNN models using the learned patient similarity to identify the top k nearest neighbors from the random training samples also had a higher best-performance (AUC: 0.95 vs. 0.89, F1-score: 0.84 vs. 0.67, and CE loss: 1.22 vs. 1.82) than those using the Euclidean distance. As the size of the similar training samples increased, which composed the most similar samples determined by the learned patient similarity, the performance of kNN models using the simple Euclidean distance to select the near neighbors degraded gradually. When exchanging the role of the Euclidean distance, and the learned patient similarity in selecting the near neighbors and similar training samples, the performance of the kNN models gradually increased. These two kinds of kNN models had the same best-performance of AUC 0.95, F1-score 0.84, and CE loss 1.22. Among the four reference models, the highest AUC and F1-score were 0.94 and 0.80, separately, which were both lower than those for the simple and similarity-based kNN models.

Conclusions: This learning-based method opened an opportunity for similarity measurement based on heterogeneous EMR data and supported the secondary use of EMR data.
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http://dx.doi.org/10.1186/s12911-021-01432-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323210PMC
July 2021

The effect of propofol on the proliferation and apoptosis of hepatocellular carcinoma cells through TGF-Β1/Smad2 signaling pathway.

Bioengineered 2021 12;12(1):4581-4592

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Anesthesiology, Peking University Cancer Hospital & Institute, Beijing, China.

Malignant tumors are a serious threat to human health. Surgical resection is the most effective treatment for liver cancer. However, liver cancer is mostly found at an advanced stage, is difficult to remove by surgery, and has a very high recurrence rate after surgery. The current liver cancer treatment drugs have serious side effects, and the treatment effect is not ideal, far from meeting the clinical needs. Based on this, this paper studies the effect of propofol on the proliferation and apoptosis of liver cancer cells through the TGF-B1/Smad2 signaling pathway, and explores the proliferation, adhesion and apoptosis of cancer cells in patients with propofol. This paper uses a comparative experiment. With medical imaging method, 80 rats with liver cancer in the same period were cultured. High-precision microscope and radiolocation method were used to observe and record the whole process of propofol regulating Smad2 signal pathway. The results show that propofol can effectively inhibit the proliferation of cancer cells in patients with liver cancer. Propofol can increase the activity and content of transforming growth factor-β1 by 12% and 20%, respectively, and then inhibit the proliferation rate of liver cancer cells by 10% through the Smad2 signaling pathway, and exponentially increase the apoptotic number of liver cancer cells. This shows that propofol has a significant inhibitory effect on the cycle of liver cancer cells. Under the action of propofol, the life cycle of liver cancer cells is shortened, which provides a certain theoretical basis for the treatment of liver cancer.
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http://dx.doi.org/10.1080/21655979.2021.1955177DOI Listing
December 2021

Patient Representation From Structured Electronic Medical Records Based on Embedding Technique: Development and Validation Study.

JMIR Med Inform 2021 Jul 23;9(7):e19905. Epub 2021 Jul 23.

School of Biomedical Engineering, Capital Medical University, Beijing, China.

Background: The secondary use of structured electronic medical record (sEMR) data has become a challenge due to the diversity, sparsity, and high dimensionality of the data representation. Constructing an effective representation for sEMR data is becoming more and more crucial for subsequent data applications.

Objective: We aimed to apply the embedding technique used in the natural language processing domain for the sEMR data representation and to explore the feasibility and superiority of the embedding-based feature and patient representations in clinical application.

Methods: The entire training corpus consisted of records of 104,752 hospitalized patients with 13,757 medical concepts of disease diagnoses, physical examinations and procedures, laboratory tests, medications, etc. Each medical concept was embedded into a 200-dimensional real number vector using the Skip-gram algorithm with some adaptive changes from shuffling the medical concepts in a record 20 times. The average of vectors for all medical concepts in a patient record represented the patient. For embedding-based feature representation evaluation, we used the cosine similarities among the medical concept vectors to capture the latent clinical associations among the medical concepts. We further conducted a clustering analysis on stroke patients to evaluate and compare the embedding-based patient representations. The Hopkins statistic, Silhouette index (SI), and Davies-Bouldin index were used for the unsupervised evaluation, and the precision, recall, and F1 score were used for the supervised evaluation.

Results: The dimension of patient representation was reduced from 13,757 to 200 using the embedding-based representation. The average cosine similarity of the selected disease (subarachnoid hemorrhage) and its 15 clinically relevant medical concepts was 0.973. Stroke patients were clustered into two clusters with the highest SI (0.852). Clustering analyses conducted on patients with the embedding representations showed higher applicability (Hopkins statistic 0.931), higher aggregation (SI 0.862), and lower dispersion (Davies-Bouldin index 0.551) than those conducted on patients with reference representation methods. The clustering solutions for patients with the embedding-based representation achieved the highest F1 scores of 0.944 and 0.717 for two clusters.

Conclusions: The feature-level embedding-based representations can reflect the potential clinical associations among medical concepts effectively. The patient-level embedding-based representation is easy to use as continuous input to standard machine learning algorithms and can bring performance improvements. It is expected that the embedding-based representation will be helpful in a wide range of secondary uses of sEMR data.
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http://dx.doi.org/10.2196/19905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367145PMC
July 2021

Supraphysiological estradiol promotes human T follicular helper cell differentiation and favours humoural immunity during in vitro fertilization.

J Cell Mol Med 2021 07 24;25(14):6524-6534. Epub 2021 May 24.

Central Laboratory, The First Hospital of Jilin University, Changchun, China.

During pregnancy, humoural immunity is essential for protection against many extracellular pathogens; however, autoimmune diseases may be induced or aggravated. T follicular helper (Tfh) cells contribute to humoural immunity. The aim of this study was to test whether Tfh cell function can be manipulated via hormones. Seventy-four women who underwent in vitro fertilization were recruited and divided into four groups: menstrual period (MP), controlled ovarian hyperstimulation (COH), embryo transfer (ET) and pregnant after embryo transfer (P). A flow cytometry analysis was performed to identify Tfh cells in peripheral blood mononuclear cells (PBMCs). Bioinformatics analysis revealed a possible pathway between Tfh and B cells. Enzyme-linked immunosorbent assays were used to detect interleukin (IL)-21 and IL-6. The quantitative polymerase chain reaction was performed to quantify BCL-6, BACH2, XBP-1, IRF-4 and G protein-coupled (GP)ER-1 mRNA expression. Compared with the MP group, the COH, ET and P groups showed more Tfh and B cells, as well as higher IL-21, IL-6, BCL-6 and BACH2 expression. Furthermore, Tfh cell frequency in PBMCs, as well as serum IL-21 and IL-6 levels, were all positively correlated with serum estradiol (E ) levels; the B cell percentage also correlated positively with Tfh cells in PBMCs. Combined with the bioinformatics analysis, XBP-1, IRF-4 and GPER-1 expression was related to E levels, both in vivo and in vitro. We speculate that E augments Tfh cells and favours humoural immunity. This study indicates that Tfh cell regulation may be a novel target in maintaining the maternal-foetal immune balance.
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http://dx.doi.org/10.1111/jcmm.16651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278094PMC
July 2021

Characteristics of purified Anti-β2GPI IgG N-glycosylation associate with thrombotic, obstetric, and catastrophic antiphospholipid syndrome.

Rheumatology (Oxford) 2021 May 20. Epub 2021 May 20.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.

Objective: Anti-β-2 glycoprotein I (anti-β2GPI) antibodies, defined as primary pathogenic antibody in antiphospholipid syndrome (APS). It has been reported that IgG Fc N-glycosylation affects IgG effector, we aim to investigate the association of Fc glycosylation profiles of purified anti-β2GP1 IgG with clinical features of APS.

Methods: We purify anti-β2GPI IgG and total IgG from 82 APS patients including 9 catastrophic antiphospholipid syndrome (CAPS) patients, as well as total IgG from 103 healthy controls to quantitatively analyze all detectable Fc N-glycanforms of all IgG subclasses with Multiple Reaction Monitoring (MRM) method based on UPLC-ESI-QqQ mass spectrometry.

Results: Both purified anti-β2GPI IgG and APS total IgG showed altered N-glycan profiles when compared with HC IgG. Anti-β2GPI IgG presented with lower galactosylation, increased bisection and core fucosylation compared with APS total IgG and HC IgG. We found higher galactosylation of aβ2GPI IgG2 in thrombotic APS compared with the obstetric APS, and lower galactosylation of aβ2GPI IgG2 associated with late pregnancy morbidity. Moreover, low galactosylation of all anti-β2GPI IgG subclasses, increased bisection and core fucosylation of anti-β2GPI IgG1/2 were strongly associated with CAPS and triple positivity of antiphospholipid antibodies (aPLs).

Conclusion: We comprehensively characterize the N-Glycans landscape of both anti-β2GP1 and total IgG in APS. Altered N-glycan profiles of anti-β2GPI IgG enables enabled the antibodies with proinflammatory properties. Furthermore, we associated levels of IgG Fc-glycosylation with clinical features antiphospholipid syndrome. These findings could increase our understanding of anti-β2GPI antibody mediated mechanisms in APS and be used to develop diagnostics and new target treatments.
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http://dx.doi.org/10.1093/rheumatology/keab416DOI Listing
May 2021

A review on China's constructed wetlands in recent three decades: Application and practice.

J Environ Sci (China) 2021 Jun 11;104:53-68. Epub 2020 Dec 11.

State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Constructed wetlands (CWs) have been introduced to and developed in China for environmental engineering over the most prosperous three decades (1990-2020). To study the origin, development process, and future trend of CWs, this review summarized a wide range of literatures between 1990 and 2020 by Chinese authors. Firstly, the publication number over years, research highlights, and the author contributions with the most published papers in this field were conducted through bibliometric analysis. Secondly, the most principal components of CWs, substrates and macrophytes were summarized and analyzed. Thirdly, the typical application cases from traditional CWs, pond systems to combined pond-wetland systems were presented. In China, CWs were predominately distributed in the east of the so-called 'Hu Huanyong Line'. Therefore CWs were limited by the socio-economic level and climatic conditions. It is unquestionable that the overall level of China's CWs has improved significantly, and one of the most prominent features has started towards the plural pattern development. There has been a trend of large-scale or low-cost CW application in the recent years. However, lifecycle research and management are required for better strategies in the future.
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http://dx.doi.org/10.1016/j.jes.2020.11.032DOI Listing
June 2021

Individual red blood cell nitric oxide production in sickle cell anemia: Nitric oxide production is increased and sickle shaped cells have unique morphologic change compared to discoid cells.

Free Radic Biol Med 2021 08 8;171:143-155. Epub 2021 May 8.

Division of Cardiology, Children's Hospital of Los Angeles, USA; Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, USA. Electronic address:

Sickle cell anemia (SCA) is characterized by decreased red blood cell (RBC) deformability due to polymerization of deoxygenated hemoglobin, leading to abnormal mechanical properties of RBC, increased cellular adhesion, and microcirculatory obstruction. Prior work has demonstrated that NO• influences RBC hydration and deformability and is produced at a basal rate that increases under shear stress in normal RBC. Nevertheless, the origin and physiological relevance of nitric oxide (NO•) production and scavenging in RBC remains unclear. We aimed to assess the basal and shear-mediated production of NO• in RBC from SCA patients and control (CTRL) subjects. RBCs loaded with a fluorescent NO• detector, DAF-FM (4-Amino-5-methylamino- 2',7'-difluorofluorescein diacetate), were imaged in microflow channels over 30-min without shear stress, followed by a 30-min period under 0.5Pa shear stress. We utilized non-specific nitric oxide synthase (NOS) blockade and carbon monoxide (CO) saturation of hemoglobin to assess the contribution of NOS and hemoglobin, respectively, to NO• production. Quantification of DAF-FM fluorescence intensity in individual RBC showed an increase in NO• in SCA RBC at the start of the basal period; however, both SCA and CTRL RBC increased NO• by a similar quantity under shear. A subpopulation of sickle-shaped RBC exhibited lower basal NO• production compared to discoid RBC from SCA group, and under shear became more circular in the direction of shear when compared to discoid RBC from SCA and CTRL, which elongated. Both CO and NOS inhibition caused a decrease in basal NO• production. Shear-mediated NO• production was decreased by CO in all RBC, but was decreased by NOS blockade only in SCA. In conclusion, total NO• production is increased and shear-mediated NO• production is preserved in SCA RBC in a NOS-dependent manner. Sickle shaped RBC with inclusions have higher NO• production and they become more circular rather than elongated with shear.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.05.007DOI Listing
August 2021

The Mechanisms of Thiosulfate Toxicity against .

Antioxidants (Basel) 2021 Apr 22;10(5). Epub 2021 Apr 22.

State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, China.

Elemental sulfur and sulfite have been used to inhibit the growth of yeasts, but thiosulfate has not been reported to be toxic to yeasts. We observed that thiosulfate was more inhibitory than sulfite to growing in a common yeast medium. At pH < 4, thiosulfate was a source of elemental sulfur and sulfurous acid, and both were highly toxic to the yeast. At pH 6, thiosulfate directly inhibited the electron transport chain in yeast mitochondria, leading to reductions in oxygen consumption, mitochondrial membrane potential and cellular ATP. Although thiosulfate was converted to sulfite and HS by the mitochondrial rhodanese Rdl1, its toxicity was not due to HS as the -deletion mutant that produced significantly less HS was more sensitive to thiosulfate than the wild type. Evidence suggests that thiosulfate inhibits cytochrome c oxidase of the electron transport chain in yeast mitochondria. Thus, thiosulfate is a potential agent against yeasts.
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http://dx.doi.org/10.3390/antiox10050646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146336PMC
April 2021

Total metabolic lesion volume of lymph nodes measured by F-FDG PET/CT: a new predictor of macrophage activation syndrome in adult-onset Still's disease.

Arthritis Res Ther 2021 03 30;23(1):97. Epub 2021 Mar 30.

Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.

Background: To investigate the potential utility of quantitative parameters obtained by F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in the assessment of disease severity and the occurrence of macrophage activation syndrome (MAS) in adult-onset Still's disease (AOSD).

Methods: Fifty-seven patients with AOSD who underwent pre-treatment F-FDG PET/CT were recruited in this study and compared with 60 age- and sex-matched healthy controls. Clinical features and laboratory data were recorded. The systemic score was assessed to determine the disease severity. The maximal standardized uptake value (SUV), metabolic lesion volume (MLV), and total lesion glycolysis (TLG) were used to evaluate the involved organs and tissues that abnormally accumulated F-FDG. Multivariate analysis was performed to identify the PET/CT-derived risk factors contributing to the AOSD-related MAS, and their diagnostic efficiency was evaluated.

Results: High F-FDG accumulation was observed in the bone marrow (SUV median, 5.10), spleen (SUV median, 3.70), and lymph nodes (LNs, SUV median, 5.55). The SUV of the bone marrow (rho = 0.376, p = 0.004), SUV of the spleen (rho = 0.450, p < 0.001), TLG of LNs (rho = 0.386, p = 0.017), and MLV of LNs (rho = 0.391, p = 0.015) were correlated with the systemic score. The SUV of the spleen (p = 0.017), TLG of LNs (p = 0.045), and MLV of LNs (p = 0.012) were higher in patients with MAS than in those without MAS. A MLV of LNs > 62.2 (OR 27.375, p = 0.042) was an independent predictive factor for MAS with a sensitivity of 80.0% and a specificity of 93.9%.

Conclusions: The glucose metabolic level of the spleen could be an effective and easy-to-use imaging indicator of disease severity, and MLV of LNs > 62.2 was a strong predictor of MAS occurrence in patients with AOSD.
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http://dx.doi.org/10.1186/s13075-021-02482-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008587PMC
March 2021

An integrated migration and transformation model to evaluate the occurrence characteristics and environmental risks of Nitrogen and phosphorus in constructed wetland.

Chemosphere 2021 Aug 13;277:130219. Epub 2021 Mar 13.

Tianjin Lingang Construction Development Co., Ltd, Tianjin, 300450, China.

In this study, an integrated migration and transformation (IMT) model based on microbial action, plant absorption, sediment release and substrate adsorption was firstly established to evaluate the temporal-spatial distribution of N and P in Lingang hybrid constructed wetland (CW), Tianjin. Compared to the conventional transformation model that only considers the microbial action, the IMT model could accurately predict the occurrence characteristics of N and P. In Lingang CW, NO-N (0.56-3.63 mg/L) was the most important form of N, and the TP was at a relatively low concentration level (0.04-0.07 mg/L). The spatial distribution results showed that a certain amount of N and P could be removed by CW. Form the temporal perspective, the N and P concentrations were greatly affected by the dissolved oxygen (DO). The simulated values obtained by IMT model indicated that the distribution of N and P was more affected by the temporality compared with the spatiality, which was consistent with measured values. Besides, the PCA indicated that TN, NO-N and DO were important factors, which affected the water quality of CW. The Nemerow pollution index method based on the simulated values indicated that Lingang CW was overall moderately polluted, and the subsurface area was the main functional unit of pollutants removal in CW. This work provides a new model for accurately predicting the occurrence characteristics of N and P pollutants in CW, which is of great significance for identifying its environmental risks and optimizing the construction of wetlands.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130219DOI Listing
August 2021

Thermal Decomposition Mechanism of GIS Basin Insulator and Kinetic Parameters-Based Lifetime Prediction Methodology.

Polymers (Basel) 2021 Feb 22;13(4). Epub 2021 Feb 22.

State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources, North China Electric Power University, Beijing 102206, China.

To reliably detect the latent defects and accurately evaluate the remaining life of gas insulated switchgear (GIS) basin insulators, more effective detection and characterization methods need to be explored. The study of pyrolysis kinetic parameters based on the intrinsic characteristics of materials provides a new way to solve this problem. First, an integral expression model of the reaction mechanism function with four parameters is proposed in this paper, which can represent various existing reaction mechanism functions with better universality and more application fields. Then, on the basis of the temperature transformation equation, an improved method for calculating the activation energy is presented, which shows higher computational accuracy than the existing methods. Further, based on a non-isothermal kinetic equation, the structure of the experimental function is given. It is a method for solving the pyrolysis reaction mechanism function of insulating materials, which can also be used to calculate the pre-exponential factor simultaneously. The thermogravimetric analysis experiment is carried out on a certain basin insulator sample at different heating rates. The pyrolysis kinetic state parameters, including the activation energy, reaction mechanism function and pre-exponential factor of the basin insulator, are calculated. Finally, the life prediction method of basin insulators is established, and the key factors affecting the life of insulators are discussed.
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http://dx.doi.org/10.3390/polym13040653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926593PMC
February 2021

Cytokine Storm in Coronavirus Disease 2019 and Adult-Onset Still's Disease: Similarities and Differences.

Front Immunol 2020 19;11:603389. Epub 2021 Jan 19.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The catastrophic outbreak of coronavirus disease 2019 (COVID-19) is currently a public emergency. Adult-onset Still's disease (AOSD) is an autoinflammatory disease characterized by life-threatening complications. Systemic hyperinflammation and cytokine storm play a critical role in the pathogenesis of both COVID-19 and AOSD. We aimed to compare the similarities and differences focusing on ferritin and cytokine levels between severe COVID-19 and active AOSD. A literature search was performed using the databases PubMed, EMBASE, and Web of Science to collect the levels of cytokine including IL-1β, IL-6, IL-18, TNF-α, IL-10, and ferritin in severe COVID-19 patients. After extracting available data of indicators of interest, we acquired these statistics with a single-arm meta-analysis. Furthermore, a comparison was conducted between 52 patients with active AOSD in our center and severe COVID-19 patients from databases. The levels of IL-6 and IL-10 were higher in severe COVID-19 compared with those in active AOSD. There were no significant differences on the cytokine of IL-1β and TNF-α. Fold changes of IL-18 were defined as the mean expression level ratio of severe COVID-19 to healthy controls in the COVID-19 study and active AOSD to healthy controls in our study, individually. Although the fold change of IL-18 in patients with AOSD was significantly higher than patients with severe COVID-19 (fold change: 594.00 vs 2.17), there was no statistical comparability. In addition, the level of ferritin was higher in active AOSD in comparison with severe COVID-19. Our findings suggest that severe COVID-19 and active AOSD have differences in cytokine panel and ferritin level, indicating the pathogenic role of ferritin in overwhelming inflammation. And it paves the way to make efficacy therapeutic strategy targeting the hyperinflammatory process in COVID-19 according to AOSD management, especially in severe COVID-19.
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http://dx.doi.org/10.3389/fimmu.2020.603389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856388PMC
February 2021

Characteristics and risk factors of relapses in patients with adult-onset Still's disease: a long-term cohort study.

Rheumatology (Oxford) 2021 Oct;60(10):4520-4529

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai and.

Objectives: To describe the detailed characteristics and explore the potential risk factors of relapses in patients with adult-onset Still's disease (AOSD).

Methods: We enrolled patients with AOSD admitted to the Department of Rheumatology and Immunology, Ruijin Hospital from August 2016 to September 2019. Kaplan-Meier curves and the log rank test were used to estimate the cumulative relapse probability and persistent remission rate before the first occurrence of relapse. The multivariate Cox proportional hazard method was utilized to identify risk factors associated with relapses of AOSD.

Results: A total of 122 patients with AOSD were enrolled with a median follow-up of 12.6 months. Among them, 26 (21.3%) patients had at least one relapse. The cumulative relapse rates of AOSD patients were 14.42%, 21.79%, 24.81% and 28.57% at 6, 12, 18 and 36 months, respectively. According to the multivariate analysis, intensive treatment (odds ratio: 6.848; 95% CI: 2.441, 19.211) and macrophage activation syndrome (odds ratio: 4.020, 95% CI: 1.564, 10.322) were associated with increased risk of relapse.

Conclusion: Our study indicated that relapses occurred in at least one-fifth of patients with AOSD, and patients with high disease severity at initial attack may have an increased risk of relapse, which needs more intensive therapy and close follow-up.
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http://dx.doi.org/10.1093/rheumatology/keab023DOI Listing
October 2021

Rituximab in thrombotic primary antiphospholipid syndrome: a pilot study from a single centre in China.

Ann Rheum Dis 2021 Jan 15. Epub 2021 Jan 15.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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http://dx.doi.org/10.1136/annrheumdis-2020-219303DOI Listing
January 2021

Use of BERT (Bidirectional Encoder Representations from Transformers)-Based Deep Learning Method for Extracting Evidences in Chinese Radiology Reports: Development of a Computer-Aided Liver Cancer Diagnosis Framework.

J Med Internet Res 2021 01 12;23(1):e19689. Epub 2021 Jan 12.

School of Biomedical Engineering, Capital Medical University, Beijing, China.

Background: Liver cancer is a substantial disease burden in China. As one of the primary diagnostic tools for detecting liver cancer, dynamic contrast-enhanced computed tomography provides detailed evidences for diagnosis that are recorded in free-text radiology reports.

Objective: The aim of our study was to apply a deep learning model and rule-based natural language processing (NLP) method to identify evidences for liver cancer diagnosis automatically.

Methods: We proposed a pretrained, fine-tuned BERT (Bidirectional Encoder Representations from Transformers)-based BiLSTM-CRF (Bidirectional Long Short-Term Memory-Conditional Random Field) model to recognize the phrases of APHE (hyperintense enhancement in the arterial phase) and PDPH (hypointense in the portal and delayed phases). To identify more essential diagnostic evidences, we used the traditional rule-based NLP methods for the extraction of radiological features. APHE, PDPH, and other extracted radiological features were used to design a computer-aided liver cancer diagnosis framework by random forest.

Results: The BERT-BiLSTM-CRF predicted the phrases of APHE and PDPH with an F1 score of 98.40% and 90.67%, respectively. The prediction model using combined features had a higher performance (F1 score, 88.55%) than those using APHE and PDPH (84.88%) or other extracted radiological features (83.52%). APHE and PDPH were the top 2 essential features for liver cancer diagnosis.

Conclusions: This work was a comprehensive NLP study, wherein we identified evidences for the diagnosis of liver cancer from Chinese radiology reports, considering both clinical knowledge and radiology findings. The BERT-based deep learning method for the extraction of diagnostic evidence achieved state-of-the-art performance. The high performance proves the feasibility of the BERT-BiLSTM-CRF model in information extraction from Chinese radiology reports. The findings of our study suggest that the deep learning-based method for automatically identifying evidences for diagnosis can be extended to other types of Chinese clinical texts.
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http://dx.doi.org/10.2196/19689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837998PMC
January 2021

A Cohort Study of Liver Involvement in Patients With Adult-Onset Still's Disease: Prevalence, Characteristics and Impact on Prognosis.

Front Med (Lausanne) 2020 23;7:621005. Epub 2020 Dec 23.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Adult-onset Still's disease (AOSD) is a systemic disorder commonly accompanied by liver involvement. This study aims to illustrate the detailed information of liver abnormalities in patients with AOSD and evaluate the impact on the prognosis. A total number of 128 hospitalized patients, who met the Yamaguchi criteria of AOSD in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2016 to August 2019 were consecutively enrolled and followed up. The demographic characteristics, clinical features, laboratory tests, treatments and prognosis were recorded. Correlations of liver function tests (LFTs) with disease activity and laboratory parameters were analyzed by the Spearman test. Risk factors of the refractory AOSD were evaluated by multivariate logistic regression analysis. Liver involvement was presented in 104 (81.3%) patients with AOSD. We observed that 34 (32.7%) patients were with mild elevation, 32 (30.8%) patients were with moderate elevation, and 38 (36.5%) patients were with severe elevation. The majority of elevated ALT, AST and ALP decreased to normal within the range of 2 months, except for GGT. Furthermore, the LFTs were found significantly correlated with disease activity. Besides, we found patients with higher levels of LFTs tended to require more intensive treatments and suffered from poorer prognosis. Multivariate logistic regression analysis showed ALP ≥ 141 IU/L and GGT ≥ 132 IU/L are independent risk factors of refractory AOSD. Liver involvement is common in patients with AOSD, the levels of LFTs are associated with disease activity and related to the treatment strategies and prognosis.
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http://dx.doi.org/10.3389/fmed.2020.621005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785871PMC
December 2020

Association of the Leukocyte Immunoglobulin-like Receptor A3 Gene With Neutrophil Activation and Disease Susceptibility in Adult-Onset Still's Disease.

Arthritis Rheumatol 2021 06 2;73(6):1033-1043. Epub 2021 May 2.

Ruijin Hospital and Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: Adult-onset Still's disease (AOSD) is a severe autoinflammatory disease. Neutrophil activation with enhanced neutrophil extracellular trap (NET) formation is involved in the pathogenesis of AOSD. Functional leukocyte immunoglobulin-like receptor A3 (LIR-A3; gene name LILRA3) has been reported to be associated with many autoimmune diseases. We aimed to investigate the association of LILRA3 with disease susceptibility and neutrophil activation in AOSD.

Methods: The LILRA3 deletion polymorphism and its tagging single-nucleotide polymorphism rs103294 were genotyped in 164 patients with AOSD and 305 healthy controls. The impact of LILRA3 on clinical features and messenger RNA expression was evaluated. Plasma levels of LIR-A3 were detected using enzyme-linked immunosorbent assay (ELISA), and the correlation between LIR-A3 plasma levels and disease activity and levels of circulating NET-DNA was investigated. LIR-A3-induced NETs were determined using PicoGreen double-stranded DNA dye and immunofluorescence analysis in human neutrophils and a neutrophil-like differentiated NB4 cell line transfected with LIR-B2 small interfering RNA.

Results: The findings from genotyping demonstrated that functional LILRA3 was a risk factor for AOSD (11% in AOSD patients versus 5.6% in healthy controls; odds ratio 2.089 [95% confidence interval 1.030-4.291], P = 0.034), and associated with leukocytosis (P = 0.039) and increased levels of circulating neutrophils (P = 0.027). Functional LILRA3 messenger RNA expression was higher in the peripheral blood mononuclear cells (P < 0.0001) and neutrophils (P < 0.001) of LILRA3 patients. Plasma levels of LIR-A3 were elevated in patients with AOSD (P < 0.0001) and correlated with disease activity indicators and levels of circulating NET-DNA complexes. Finally, enhanced NET formation was identified in neutrophils from healthy controls and patients with inactive AOSD after stimulation of the neutrophils with LIR-A3. Moreover, NET formation was impaired in NB4 cells after knockdown of LILRB2 gene expression.

Conclusion: Our study provides the first evidence that functional LILRA3 is a novel genetic risk factor for the development of AOSD and that functional LIR-A3 may play a pathogenic role by inducing formation of NETs.
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http://dx.doi.org/10.1002/art.41635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252061PMC
June 2021

Pregnancy Outcomes in Patients With Adult-Onset Still's Disease: A Cohort Study From China.

Front Med (Lausanne) 2020 8;7:566738. Epub 2020 Dec 8.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Adult-onset Still's disease (AOSD) is an autoinflammatory disease with a higher prevalence rate in young females. The purpose of this study is to investigate whether AOSD has an adverse impact on pregnancy outcomes, or conversely exacerbated by pregnancy. The outcomes of 191 pregnancies were evaluated in 86 female patients with AOSD. The generalized linear mixed model and propensity score matching method were conducted to evaluate the influence of AOSD on pregnancy outcomes. A dependent sample sign test was applied to assess the impact of pregnancy on the relapse of AOSD. The results showed that the post-AOSD group had a lower proportion of normal delivery (25.0 vs. 52.4%, = 0.036) and a higher proportion of spontaneous abortion (STA) (18.8 vs. 0.6%, = 0.002) compared with the pre-AOSD group. Moreover, pregnancy after being diagnosed with AOSD was a significant high risk factor of STA (adjusted OR = 4.577, 95% CI: 4.166-845.119; = 0.003). Disease flare upon conception was observed in one of 16 post-AOSD pregnancies ( = 1.000). There were 11 patients with new-onset AOSD during gestation or postpartum, among which five (45.4%) evolved into the polycyclic course. AOSD patients might suffer from a higher risk of STA, however, pregnancy might not be related with the exacerbation of diagnosed AOSD. New-onset AOSD during gestation or postpartum tend to evolve into the polycyclic course.
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http://dx.doi.org/10.3389/fmed.2020.566738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753176PMC
December 2020

Synthesis of heterocyclic compounds through nucleophilic phosphine catalysis.

Chem Commun (Camb) 2020 Dec 7;56(97):15235-15281. Epub 2020 Dec 7.

Department of Chemistry and Innovation Center of Pesticide Research, China Agricultural University, Beijing 100193, China.

Nucleophilic phosphine catalysis is a practical and powerful tool for the synthesis of various heterocyclic compounds with the advantages of environmentally friendly, metal-free, and mild reaction conditions. The present report summarizes the construction of four to eight-membered heterocyclic compounds containing nitrogen, oxygen and sulphur atoms through phosphine-catalyzed intramolecular annulations and intermolecular [2+2], [3+2], [4+1], [3+1+1], [5+1], [4+2], [2+2+2], [3+3], [4+3] and [3+2+3] annulations of electron-deficient alkenes, allenes, alkynes and Morita-Baylis-Hillman carbonates.
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http://dx.doi.org/10.1039/d0cc05699eDOI Listing
December 2020

Loss of alpha-globin genes in human subjects is associated with improved nitric oxide-mediated vascular perfusion.

Am J Hematol 2021 03 12;96(3):277-281. Epub 2020 Dec 12.

Division of Hematology/Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.

Alpha thalassemia is a hemoglobinopathy due to decreased production of the α-globin protein from loss of up to four α-globin genes, with one or two missing in the trait phenotype. Individuals with sickle cell disease who co-inherit the loss of one or two α-globin genes have been known to have reduced risk of morbid outcomes, but the underlying mechanism is unknown. While α-globin gene deletions affect sickle red cell deformability, the α-globin genes and protein are also present in the endothelial wall of human arterioles and participate in nitric oxide scavenging during vasoconstriction. Decreased production of α-globin due to α-thalassemia trait may thereby limit nitric oxide scavenging and promote vasodilation. To evaluate this potential mechanism, we performed flow-mediated dilation and microvascular post-occlusive reactive hyperemia in 27 human subjects (15 missing one or two α-globin genes and 12 healthy controls). Flow-mediated dilation was significantly higher in subjects with α-trait after controlling for age (P = .0357), but microvascular perfusion was not different between groups. As none of the subjects had anemia or hemolysis, the improvement in vascular function could be attributed to the difference in α-globin gene status. This may explain the beneficial effect of α-globin gene loss in sickle cell disease and suggests that α-globin gene status may play a role in other vascular diseases.
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http://dx.doi.org/10.1002/ajh.26058DOI Listing
March 2021

Circulating Neutrophil Extracellular Traps Signature for Identifying Organ Involvement and Response to Glucocorticoid in Adult-Onset Still's Disease: A Machine Learning Study.

Front Immunol 2020 9;11:563335. Epub 2020 Nov 9.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Adult-onset Still's disease (AOSD) is an autoinflammatory disease with multisystem involvement. Early identification of patients with severe complications and those refractory to glucocorticoid is crucial to improve therapeutic strategy in AOSD. Exaggerated neutrophil activation and enhanced formation of neutrophil extracellular traps (NETs) in patients with AOSD were found to be closely associated with etiopathogenesis. In this study, we aim to investigate, to our knowledge for the first time, the clinical value of circulating NETs by machine learning to distinguish AOSD patients with organ involvement and refractory to glucocorticoid. Plasma samples were used to measure cell-free DNA, NE-DNA, MPO-DNA, and citH3-DNA complexes from training and validation sets. The training set included 40 AOSD patients and 24 healthy controls (HCs), and the validation set included 26 AOSD patients and 16 HCs. Support vector machines (SVM) were used for modeling and validation of circulating NETs signature for the diagnosis of AOSD and identifying patients refractory to low-dose glucocorticoid treatment. The training set was used to build a model, and the validation set was used to test the predictive capacity of the model. A total of four circulating NETs showed similar trends in different individuals and could distinguish patients with AOSD from HCs by SVM (AUC value: 0.88). Circulating NETs in plasma were closely correlated with systemic score, laboratory tests, and cytokines. Moreover, circulating NETs had the potential to distinguish patients with liver and cardiopulmonary system involvement. Furthermore, the AUC value of combined NETs to identify patients who were refractory to low-dose glucocorticoid was 0.917. In conclusion, circulating NETs signature provide added clinical value in monitoring AOSD patients. It may provide evidence to predict who is prone to be refractory to low-dose glucocorticoid and help to make efficient therapeutic strategy.
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http://dx.doi.org/10.3389/fimmu.2020.563335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680913PMC
May 2021

Anti-Tyro3 IgG Associates with Disease Activity and Reduces Efferocytosis of Macrophages in New-Onset Systemic Lupus Erythematosus.

J Immunol Res 2020 10;2020:2180708. Epub 2020 Nov 10.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Systemic lupus erythematosus (SLE) is a disease characterized by the production of a large number of autoantibodies. Defected phagocytosis of macrophage plays an important role in innate immunity in the pathogenesis of SLE. Tyro3 is a receptor responsible for the recognition of apoptotic cells during efferocytosis by macrophages. To investigate the role of Tyro3 receptor in macrophages' efferocytosis of apoptotic cells in SLE, we aimed to reveal the clinical relevance and impact of Tyro3 autoantibody on SLE.

Methods: The serum levels of IgG-type autoantibody against Tyro3 receptor were detected in new-onset, treatment-naïve SLE patients ( = 70), rheumatoid arthritis (RA) ( = 24), primary Sjögren's Syndrome (pSS) ( = 21), and healthy controls (HCs) ( = 70) using enzyme-linked immunosorbent assay (ELISA). The effects of purified Tyro3 autoantibody from SLE patients on the efferocytosis of human monocyte-derived macrophages were measured by flow cytometry and immunofluorescence.

Results: The serum levels of IgG-type autoantibody against Tyro3 receptor were significantly elevated in patients with SLE compared to RA, pSS, and HCs (all < 0.0001). The levels of anti-Tyro3 IgG were positively associated with the SLE disease activity index (SLEDAI) score ( = 0.254, = 0.034), erythrocyte sedimentation rate (ESR) ( = 0.430, < 0.001), C-reactive protein (CRP) ( = 0.246, = 0.049), and immunoglobulin G (IgG) ( = 0.408, = 0.001) and negatively associated with haemoglobin (Hb) ( = -0.294, = 0.014). ROC curves illustrated that the anti-Tyro3 antibody could differentiate patients with SLE from HCs. Furthermore, flow cytometry and immunofluorescence demonstrated that purified anti-Tyro3 IgG inhibited the efferocytosis of macrophages ( = 0.004 and 0.044, respectively) compared with unconjugated human IgG.

Conclusions: These observations indicated that autoantibody against Tyro3 was associated with disease activity and could impair efferocytosis of macrophages. It might be a potential novel disease biomarker and might be involved in the pathogenesis of SLE.
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http://dx.doi.org/10.1155/2020/2180708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673931PMC
August 2021

CRISPR-ERA: A Webserver for Guide RNA Design of Gene Editing and Regulation.

Methods Mol Biol 2021 ;2189:65-69

Ministry of Education Key Laboratory of Bioinformatics, Tsinghua University, Beijing, China.

The CRISPR/Cas9 system has been developed as a powerful technology for both targeted genome editing and gene regulation. However, the design of efficient single-guide RNAs (sgRNAs) remains challenging with the consideration of many criteria. In this section, we introduce how to design sgRNA sequences and build genome-wide sgRNA library using CRISPR-ERA, which is one of the state-of-the-art designer webserver tools for sgRNA design based on a set of sgRNA design rules summarized from published reports.
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http://dx.doi.org/10.1007/978-1-0716-0822-7_5DOI Listing
March 2021

Effects of crystal structure and plane orientation on lithium and nickel co-doped spinel lithium manganese oxide for long cycle life lithium-ion batteries.

J Colloid Interface Sci 2021 Mar 21;585:729-739. Epub 2020 Oct 21.

National and Local Joint Engineering Research Center for Green Preparation Technology of Biobased Materials, Yunnan Minzu University, Kunming 650500, China; Key Laboratory of Green-chemistry Materials in University of Yunnan Province, Yunnan Minzu University, Kunming 650500, China.

Various Li-rich spinel LiNiMnO (0 ≤ x ≤ 0.10) cathode materials with a truncated octahedron were synthesized by a solution combustion method. The relationship of crystalline structure, particles morphology and electrochemical properties of the as-prepared samples was investigated via a series of physicochemical characterizations. The Li-Ni co-doping changes the lattice parameters and atomic configuration, whilst resulting in a contraction of unit cell dimension and giving rise to a variation of bond length. In this regard, the shrinkage of octahedral MnO provides a robust structure and the expansion of tetrahedral LiO facilitates a fast electrochemical process. Additionally, the resulted polyhedral LiNiMnO samples present the exposed (110), (100), and (111) crystal planes, which provide the favorable Li ions diffusion/transmission channel and alleviate Mn dissolution. Owing to these merits of polyhedral structure and Li-Ni co-doping, the optimized LiNiMnO exhibits good electrochemical performance with high initial discharge capacity of 119.8, 107.1 and 97.9 mAh·g at 1, 5 and 10 C, respectively. Even at a high current rate of 15 C, an excellent capacity retention of 91.7% is obtained after 1000 cycles, whilst the high temperature performance was also improved.
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http://dx.doi.org/10.1016/j.jcis.2020.10.052DOI Listing
March 2021
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