Publications by authors named "Fang Chen"

1,848 Publications

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M1 macrophage-derived exosomes impair beta cell insulin secretion via miR-212-5p by targeting SIRT2 and inhibiting Akt/GSK-3β/β-catenin pathway in mice.

Diabetologia 2021 Jun 11. Epub 2021 Jun 11.

Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.

Aims/hypothesis: Macrophage levels are elevated in pancreatic islets, and the resulting inflammatory response is a major contributor to beta cell failure during obesity and type 2 diabetes mellitus. Previous studies by us and others have reported that exosomes released by macrophages play important roles in mediating cell-to-cell communication, and represent a class of inflammatory factors involved in the inflammatory process associated with type 2 diabetes mellitus. However, to date, no reports have demonstrated the effect of macrophage-derived exosomes on beta cells, and little is known regarding their underlying mechanisms in beta cell injury. Thus, we aimed to study the impact of macrophage-derived exosomes on islet beta cell injury in vitro and in vivo.

Methods: The phenotypic profiles of islet-resident macrophages were analysed in C57BL/6J mice fed a high-fat diet (HFD). Exosomes were collected from the medium of cultured bone marrow-derived macrophages (BMDMs) and from isolated islet-resident macrophages of HFD-fed mice (HFD-Exos). The role of exosomes secreted by inflammatory M1 phenotype BMDMs (M1-Exos) and HFD-Exos on beta cell function was assessed. An miRNA microarray and quantitative real-time PCR (qPCR) were conducted to test the level of M1-Exos-derived miR-212-5p in beta cells. Then, miR-212-5p was overexpressed or inhibited in M1-Exos or beta cells to determine its molecular and functional impact.

Results: M1-polarised macrophages were enriched in the islets of obese mice. M1 macrophages and islet-resident macrophages of HFD-fed mice impaired beta cell insulin secretion in an exosome-dependent manner. miR-212-5p was notably upregulated in M1-Exos and HFD-Exos. Enhancing the expression of miR-212-5p impaired beta cell insulin secretion. Blocking miR-212-5p elicited a significant improvement in M1-Exos-mediated beta cell insulin secretion during injury. Mechanistically, M1-Exos mediated an intercellular transfer of the miR-212-5p, targeting the sirtuin 2 gene and regulating the Akt/GSK-3β/β-catenin pathway in recipient beta cells to restrict insulin secretion.

Conclusions/interpretation: A novel exosome-modulated mechanism was delineated for macrophage-beta cell crosstalk that drove beta cell dysfunction and should be explored for its therapeutic utility.
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http://dx.doi.org/10.1007/s00125-021-05489-1DOI Listing
June 2021

Neutrophil extracellular traps impair intestinal barrier functions in sepsis by regulating TLR9-mediated endoplasmic reticulum stress pathway.

Cell Death Dis 2021 Jun 11;12(6):606. Epub 2021 Jun 11.

Division of Trauma and Surgical Intensive Care Unit, Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, P. R. China.

Increased neutrophil extracellular traps (NETs) formation has been found to be associated with intestinal inflammation, and it has been reported that NETs may drive the progression of gut dysregulation in sepsis. However, the biological function and regulation of NETs in sepsis-induced intestinal barrier dysfunction are not yet fully understood. First, we found that both circulating biomarkers of NETs and local NETs infiltration in the intestine were significantly increased and had positive correlations with markers of enterocyte injury in abdominal sepsis patients. Moreover, the levels of local citrullinated histone 3 (Cit H3) expression were associated with the levels of BIP expression. To further confirm the role of NETs in sepsis-induced intestinal injury, we compared peptidylarginine deiminase 4 (PAD4)-deficient mice and wild-type (WT) mice in a lethal septic shock model. In WT mice, the Cit H3-DNA complex was markedly increased, and elevated intestinal inflammation and endoplasmic reticulum (ER) stress activation were also found. Furthermore, PAD4 deficiency alleviated intestinal barrier disruption and decreased ER stress activation. Notably, NETs treatment induced intestinal epithelial monolayer barrier disruption and ER stress activation in a dose-dependent manner in vitro, and ER stress inhibition markedly attenuated intestinal apoptosis and tight junction injury. Finally, TLR9 antagonist administration significantly abrogated NETs-induced intestinal epithelial cell death through ER stress inhibition. Our results indicated that NETs could contribute to sepsis-induced intestinal barrier dysfunction by promoting inflammation and apoptosis. Suppression of the TLR9-ER stress signaling pathway can ameliorate NETs-induced intestinal epithelial cell death.
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http://dx.doi.org/10.1038/s41419-021-03896-1DOI Listing
June 2021

Transcriptional responses of four slc30a/znt family members and their roles in Zn homeostatic modulation in yellow catfish Pelteobagrus fulvidraco.

Biochim Biophys Acta Gene Regul Mech 2021 Jun 8:194723. Epub 2021 Jun 8.

Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan 430070, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China. Electronic address:

The study characterized their regulatory functions of four znt members (znt1, znt2, znt6 and znt8) in Zn homeostasis in vertebrates. We found that the -1281/-1296 bp locus on the znt1 promoter, the -1/-16 bp locus on the znt2 promoter, the -825/-839 bp locus on the znt6 promoter, the -165/-180 bp locus and the -274/-292 bp STAT3 locus on the znt8 promoter were functional MTF-1 binding sites and had metal responsive element (MRE). Zn incubation increased activities of four znt promoters, which was mediated by MRE sites on znt1, znt2, znt6 and znt8 promoters and by STAT3 binding site on znt8 promoter. Moreover, Zn activated the transcription of these znts genes through MTF-1-MRE-dependent pathway. Zn incubation up-regulated the mRNA and total protein expression of ZnT1, ZnT2 and ZnT8 at both 24 h and 48 h. Overall, for the first time, this study offered novel insights for regulatory mechanism of Zn homeostasis in vertebrates.
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http://dx.doi.org/10.1016/j.bbagrm.2021.194723DOI Listing
June 2021

Host-guest Interaction in Ethylene and Ethane Separation on Zeolitic Imidazolate Frameworks as Revealed by Solid-State NMR Spectroscopy.

Chemistry 2021 Jun 10. Epub 2021 Jun 10.

Chinese Academy of Sciences, Wuhan Institute of Physics and Mathematics, CHINA.

The separation of ethane/ethylene mixture using MOFs as adsorbents is strongly associated with the pore size-sieving effect and the adsorbent-adsorbate interaction. Herein, solid-state NMR spectroscopy is utilized to explore the host-guest interaction and ethane/ethylene separation mechanism on zeolitic imidazolate frameworks (ZIFs). Preferential access to the ZIF-8 and ZIF-8-90 frameworks by ethane compared to ethylene is directly visualized from two-dimensional 1 H- 1 H spin diffusion MAS NMR spectroscopy and further verified by computational density distributions. The 1 H MAS NMR spectroscopy provides an alternative for straightforwardly extracting the adsorption selectivity of ethane/ethylene mixture at 1.1~9.6 bar in ZIFs, which is consistent with the IAST predictions.
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http://dx.doi.org/10.1002/chem.202101779DOI Listing
June 2021

Endoscopic coblation treatment for congenital pyriform sinus fistula in children.

Medicine (Baltimore) 2021 May;100(19):e25942

Department of Otolaryngology-Head and Neck Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.

Abstract: Congenital pyriform sinus fistula (CPSF) is a very rare branchial apparatus malformation. Traditional open surgery for fistulectomy might fail to excise the lesion completely, leading to continual recurrence. Herein, we report our experience of endoscopic coblation technique for treatment of CPSF in children.To observe the clinical efficacy of endoscopic coblation treatment of CPSF in children, especially for those in acute infection stage.Retrospective case series with 54 patients (including 20 cases in acute infection stage and 34 cases in non infection stage) who were diagnosed with CPSF between October 2017 to November 2019, all patients were treated with endoscopic coblation to close the piriform fossa fistula, neck abscess incision and drainage performed simultaneously for acute infection stage cases. Data collected including age of diagnosis, presenting symptoms, diagnostic methods, prior and subsequent treatments, length of hospitalization, and recurrence were analyzed.Of the 20 cases in acute infection stage, there were 3 children with transient vocal cord paresis all of which resolved with 1 month. Four children of the 34 cases in non infection stage appeared reddish swelling of the neck on the 4th, 5th, 6th, and 7th days after coblation and then underwent abscess incision and drainage. All cases experienced no recurrence, vocal cord paralysis, pharyngeal fistula and massive hemorrhage after their first endoscopic coblation of the sinus tract in the follow up of 3 to 28 months.Endoscopic coblation is an effective and safe approach for children with CPSF, neck abscess incision and drainage could be performed simultaneously in acute infection stage. We advocate using this minimally invasive technique as first line of treatment for CPSF.
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http://dx.doi.org/10.1097/MD.0000000000025942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133172PMC
May 2021

Circular RNA PVT1 silencing prevents ischemia-reperfusion injury in rat by targeting microRNA-125b and microRNA-200a.

J Mol Cell Cardiol 2021 Jun 4. Epub 2021 Jun 4.

Cardiovascular Surgery Ward, The First Affiliated Hospital of Guangxi Medical University, China. Electronic address:

Circular RNAs (circRNAs) are essential regulators associated with many cardiac conditions, including myocardial infarction (MI). This study aimed to explore circRNA expression during MI development in an animal model and in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. Microarray and real-time quantitative PCR showed that the circRNA PVT1 (circPVT1) was expressed at high levels in MI tissues and H/R-triggered cardiomyocytes. Loss-of-function assays were utilized for examining the influence of circPVT1 on cardiac function and cardiomyocyte properties. Cardiac function was measured by echocardiography at 7 d after MI. Reduced circPVT1 expression significantly decreased MI-triggered myocardial infarct size by 60% and prevented MI-triggered reductions in fractional shortening (%FS) and ejection fraction (EF%). Results of LDH, CCK-8, EdU staining, colony formation assays, and flow cytometry showed that circPVT1 silencing restored cell viability and proliferation while decreased apoptosis. Mechanistic experiments indicated that microRNAs (miR)-125b and miR-200a associated with circPVT1. We demonstrated that circPVT1 functioned as a competitive endogenous RNA (ceRNA) to sponge both miR-125b and miR-200a. Gain-of-function assays showed that miR-125b and miR-200a upregulation partially eliminated the effects of circPVT1 on cardiomyocyte properties. In addition, we found that the previously reported p53/TRAF6, SIRT7, Keap1/Nrf2, and PDCD4 pathways were regulated by the circPVT1/miR-125b/miR-200a axis. In conclusion, our study suggests that circPVT1 protects the myocardium from MI and H/R injury by preventing miR-125b- and miR-200a-mediated apoptotic signaling.
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http://dx.doi.org/10.1016/j.yjmcc.2021.05.019DOI Listing
June 2021

Pressure and Temperature Combined With Microbial Supernatant Effectively Inactivate Spores.

Front Microbiol 2021 18;12:642501. Epub 2021 May 18.

College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, China.

Spores from the species pose a challenge to the food industry because of their ubiquitous nature and extreme resistance. Accumulated evidence indicates that it is effective to induce spore germination homogenously before killing them. However, it is difficult to obtain and apply exogenous germination factors, which will affect food composition. Therefore, this study screened endogenous germinants from microorganisms by assessing the effect of , , , , and cultures (cell-free) on spore germination. The results showed that the supernatants from these five microorganisms induced spore germination instead of sediments. Moreover, the supernatants of , , and exhibited higher germination rates than and , and the induction effects were concentration-dependent. Furthermore, plate counting confirmed that the microbial supernatants induced the lowest spore germination ratio on strains FB85 [germination receptors (GRs) mutant] but not strains PB705 (PrkC mutant). In addition, and supernatants, combined with pressure and temperature, were effective in spore inactivation. The findings suggested that microbial supernatants may include agents that induce spore germination and may be used for spore inactivation.
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http://dx.doi.org/10.3389/fmicb.2021.642501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169991PMC
May 2021

Effects of semi-permeable membrane covering coupled with intermittent aeration on gas emissions during aerobic composting from the solid fraction of dairy manure at industrial scale.

Waste Manag 2021 Jun 3;131:1-9. Epub 2021 Jun 3.

Engineering Laboratory for AgroBiomass Recycling & Valorizing, College of Engineering, China Agricultural University, Beijing 100083, China. Electronic address:

In this study, the effects of covering the compost pile with a semi-permeable membrane in combination with intermittent aeration on the gas emissions during aerobic composting from the solid fraction of dairy manure at industrial scale were investigated. A large-scale composting experiment was carried out to compare a membrane-covered (CT) group with a control (CK) group. The results indicated that the CT group could maintain a suitable aerobic and positive micro-pressure environment. The carbon dioxide, methane, nitrous oxide, and ammonia emissions outside the membrane during the aeration interval were reduced by 64.23%, 70.07%, 54.87%, and 11.32%, respectively, compared with that inside the membrane. It was also determined that the methane and nitrous oxide emissions from the CT group were reduced by 99.89% and 60.48% relative to the CK group, confirming that the combined process represented a novel strategy for reducing gas emissions during dairy manure composting.
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http://dx.doi.org/10.1016/j.wasman.2021.05.030DOI Listing
June 2021

Ambulatory risk models for long-term prevention of sepsis: Retrospective Analysis and Predictive Model.

JMIR Med Inform 2021 Jun 2. Epub 2021 Jun 2.

Institute for Systems Biology, 401 Terry Ave NInstitute for Systems Biology, Seattle, US.

Background: Sepsis is a life-threatening syndrome that can rapidly lead to organ damage and death. Existing risk scores predict outcomes for patients who have already become acutely ill.

Objective: Our objective is to develop a model to identify patients at risk of getting sepsis within two years, to support reduction of sepsis morbidity and mortality.

Methods: Machine learning was applied to 2,683,049 electronic health records (EHRs) with over 64 million encounters across five states to develop models for predicting a patient's risk of getting sepsis within two years. Features were selected to be easily obtainable from a patient's chart in real-time during ambulatory encounters.

Results: Models showed consistent prediction scores, with the highest AUROC of 0.82 and positive likelihood ratio of 2.9 achieved with gradient boosting on all features combined. Predictive features included age, sex, ethnicity, average ambulatory heart rate, standard deviation of body mass index, and the number of prior medical conditions and procedures. Results identified both known and potential new risk factors for long-term sepsis. Model variations also illustrated trade-offs between incrementally higher accuracy, implementability and interpretability.

Conclusions: Accurate, implementable models were developed to predict two-year risk of sepsis, using EHR data that is easy to obtain from ambulatory encounters. These results help advance understanding of sepsis and provide a foundation for future trials of risk-informed preventive care.

Clinicaltrial:
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http://dx.doi.org/10.2196/29986DOI Listing
June 2021

Checkpoint kinases are required for oocyte meiotic progression by the maintenance of normal spindle structure and chromosome condensation.

Exp Cell Res 2021 May 31;405(2):112657. Epub 2021 May 31.

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. Electronic address:

Checkpoint kinases (Chk) 1/2 are known for DNA damage checkpoint and cell cycle control in somatic cells. According to recent findings, the involvement of Chk1 in oocyte meiotic resumption and Chk2 is regarded as an essential regulator for progression at the post metaphase I stage (MI). In this study, AZD7762 (Chk1/2 inhibitor) and SB218078 (Chk1 inhibitor) were used to uncover the joint roles of Chk1/2 and differentiate the importance of Chk1 and Chk2 during oocyte meiotic maturation. Inhibition of Chk1/2 or Chk1 alone had no significant effect on germinal vesicle breakdown (GVBD) but significantly inhibited the first polar body (PB1). Interestingly, inhibition of Chk1 alone could not increase or completely block the extrusion of PB1 like Chk1/2 inhibition. Also, Chk1/2 inhibition resulted in defective meiotic spindle organization and chromosome condensation both in MI and metaphase II (MII) stages of oocytes. The location of γ-tubulin and Securin were abnormal or missing, while P38 MAPK was activated by Chk1/2 inhibition. Meanwhile, Chk1/2 inhibition reduced the percentage of the second polar body extrusion and pronuclear formation. In conclusion, our results further understand the functions and regulatory mechanism of Chk1/2 during oocyte meiotic maturation.
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http://dx.doi.org/10.1016/j.yexcr.2021.112657DOI Listing
May 2021

Artemisinin Protects Porcine Mammary Epithelial Cells against Lipopolysaccharide-Induced Inflammatory Injury by Regulating the NF-κB and MAPK Signaling Pathways.

Animals (Basel) 2021 May 24;11(6). Epub 2021 May 24.

Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.

Artemisinin performs a variety of biological functions, such as anti-cancer, anti-inflammatory, anti-viral, and anti-oxidant effects. However, the effects of artemisinin on sow mastitis have not been studied. The results of the current study showed that mRNA expression abundance and content of the inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were significantly increased when using 50 μg/mL LPS to stimulate pMECs for 24 h ( < 0.05). Pretreatment with 20 μM artemisinin weakened LPS-induced inflammatory damage in pMECs and decreased mRNA expression abundance and the content of inflammatory factors (IL-1β, IL-6, and TNF-α) in pMECs ( < 0.05). Mechanistically, artemisinin inhibited LPS-induced activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. In summary, the pretreatment of pMECs with artemisinin showed enhanced anti-inflammatory activity against LPS-induced inflammation.
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http://dx.doi.org/10.3390/ani11061528DOI Listing
May 2021

Follow-up study of pulmonary function among COVID-19 survivors 1 year after recovery.

J Infect 2021 May 29. Epub 2021 May 29.

Department of Emergency Medicine, Hunan Provincial Institute of Emergency Medicine, Hunan Provincial Key Laboratory of Emergency and Critical Care Metabonomics, Hunan Provincial People's Hospital/The First Affiliated Hospital, Hunan Normal University, Changsha, Hunan, China; School of Life Sciences, Hunan Normal University, Changsha, Hunan, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.05.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164517PMC
May 2021

Long Noncoding RNA HCG11 Acts as a Tumor Suppressor in Gastric Cancer by Regulating miR-942-5p/BRMS1 Axis.

J Oncol 2021 11;2021:9961189. Epub 2021 May 11.

Oncology Department (II), Qingdao Central Hospital, Qingdao University, Qingdao 266042, China.

The functions of long noncoding RNAs (lncRNAs) have been widely investigated in human cancers, including gastric cancer (GC). The purpose of this study was to elucidate the role of lncRNA HCG11 in GC. In this study, mRNA and protein expressions were detected by quantitative real-time polymerase chain reaction assays (RT-qPCR) and Western blot analysis. The proliferation ability of GC cells was examined by (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyl Tetrazolium Bromide) MTT assays. The invasion and migration abilities of GC cells were evaluated by Transwell assays. The binding sites between miR-942-5p and HCG11/BRMS1 were confirmed by dual-luciferase reporter assays. Results showed that LncRNA HCG11 was downregulated in GC cells. Functionally, overexpression of HCG11 inhibited GC cell proliferation, migration, and invasion. In addition, lncRNA HCG11 was found to act as a molecular sponge of miR-942-5p. Furthermore, miR-942-5p promoted GC progression by suppressing lncRNA HCG11 expression. Besides that, BRMS1 was confirmed as a direct target of miR-942-5p. More importantly, breast cancer metastasis suppressor 1 (BRMS1) inhibited GC progression by upregulating lncRNA HCG11 and downregulating miR-942-5p. In conclusion, LncRNA HCG11 inhibited cell proliferation, migration, and invasion in GC by sponging miR-942-5p and upregulating BRMS1.
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http://dx.doi.org/10.1155/2021/9961189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131154PMC
May 2021

Single-cell brain atlas of Parkinson's disease mouse model.

J Genet Genomics 2021 Feb 18. Epub 2021 Feb 18.

BGI-Shenzhen, Shenzhen 518083, China. Electronic address:

Parkinson's disease (PD) is a neurodegenerative disease, leading to the impairment of movement execution. PD pathogenesis has been largely investigated, either limited to bulk transcriptomic levels or at certain cell types, which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types. Here, we report the application of single-nucleus RNA-seq on midbrain, striatum, and cerebellum of the α-syn-A53T mouse, a well-established PD mouse model, and matched controls, generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells. Additionally, we comprehensively depicted the dysfunctions in PD pathology, covering the elevation of NF-κB activity, the alteration of ion channel components, the perturbation of protein homeostasis network, and the dysregulation of glutamatergic signaling. Notably, we identified a variety of cell types closely associated with PD risk genes. Taken together, our study provides valuable resources to systematically dissect the molecular mechanism of PD pathogenesis at the single-cell resolution, which facilitates the development of novel approaches for diagnosis and therapies against PD.
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http://dx.doi.org/10.1016/j.jgg.2021.01.003DOI Listing
February 2021

Prothrombotic variants as modifiers of clinical phenotype in four related individuals with haemophilia A.

Haemophilia 2021 May 29. Epub 2021 May 29.

Division of Hematology and Oncology, Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA.

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http://dx.doi.org/10.1111/hae.14348DOI Listing
May 2021

Influence of low tumor content on tumor mutational burden estimation by whole-exome sequencing and targeted panel sequencing.

Clin Transl Med 2021 May;11(5):e415

Department of In Vitro Diagnostic Reagent, National Institutes for Food And Drug Control (NIFDC), Beijing, China.

Background: Tumor mutational burden (TMB) is a promising biomarker for stratifying patient subpopulation who would benefit from immune checkpoint blockade (ICB) therapies. Although great efforts have been made for standardizing TMB measurement, mutation calling and TMB quantification can be challenging in samples with low tumor content including liquid biopsies. The effect of varying tumor content on TMB estimation by different assay methods has never been systematically investigated.

Method: We established a series of reference standard DNA samples derived from 11 pairs of tumor-normal matched human cell lines across different cancer types. Each tumor cell line was mixed with its matched normal at 0% (control), 1%, 2%, 5%, and 10% mass-to-mass ratio to mimic the clinical samples with low tumor content. TMB of these reference standards was evaluated by both ∼1000× whole-exome sequencing (wesTMB) and targeted panel sequencing (psTMB) at four different vendors. Both regression and classification analyses of TMB were performed for theoretical investigation and clinical practice purposes.

Results: Linear regression model was established that demonstrated in silico psTMB determined by regions of interest (ROI) as a great representative of wesTMB based on TCGA dataset. It was also true in our reference standard samples as the predicted psTMB interval based on the observed wesTMB captured the intended 90% of the in silico psTMB values. Although ∼1000× deep WES was applied, reference standard samples with less than 5% of tumor proportions are below the assay limit of detection (LoD) of wesTMB quantification. However, predicted wesTMB based on observed psTMB accurately classify (>0.97 AUC) for TMB high and low patient stratification even in samples with 2% of tumor content, which is more clinically relevant, as TMB determination should be a qualitative assay for TMB high and low patient classification. One targeted panel sequencing vendor using an optimized blood psTMB pipeline can further classify TMB status accurately (>0.82 AUC) in samples with only 1% of tumor content.

Conclusions: We developed a linear model to establish the quantitative correlation between wesTMB and psTMB. A set of DNA reference standards was produced in aid to standardize TMB measurements in samples with low tumor content across different targeted sequencing panels. This study is a significant contribution aiming to harmonize TMB estimation and extend its future application in clinical samples with low tumor content including liquid biopsy.
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http://dx.doi.org/10.1002/ctm2.415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102856PMC
May 2021

A feasible electrochemical biosensor for determination of glucose based on Prussian blue - Enzyme aggregates cascade catalytic system.

Bioelectrochemistry 2021 May 6;141:107838. Epub 2021 May 6.

The Key Laboratory of Space Applied Physics and Chemistry, Ministry of Education, Northwestern Polytechnical University, Xi'an 710129, PR China.

The coral-like gold micro/nanostructures were formed onto carbon cloth followed by a Prussian blue (PB) electrochemical deposition to construct a highly sensitive HO biosensor. The SEM image of PB/Au/CC showed the coral-like gold morphology, and EDS and XPS tests also further confirmed the successful loading of Au and PB. The electrochemical tests of PB/Au/CC displayed the electrode possessed excellent performance in sensing HO, which was quantified in the linear range from 0.002 to 13.97 mM at an applied potential of -0.05 V, with a sensitivity of 454.97 μA mM cm and a detection limit of 0.5 μM (S/N = 3). And then a convenient sensing platform was established via the cross-linking enzyme aggregates method, using PB as the mediator to realize the construction of glucose BIOSENSOR [email protected]/Au/CC. The biosensor responded to glucose in the sensitivity of 70.76 μA mM cm within the linear range from 0.05 to 3.15 mM with a detection limit of 10 μM. The sensitivity was much higher than the electrode constructed by the cross-linking enzyme method ([email protected]/Au/CC), and it was also highly selective, reproducible, and stable. Besides, the proposed biosensor was successfully applied to the glucose determination in real human serum samples, which proved its practicability.
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http://dx.doi.org/10.1016/j.bioelechem.2021.107838DOI Listing
May 2021

Novel advances in understanding fatty acid-binding G protein-coupled receptors and their roles in controlling energy balance.

Nutr Rev 2021 May 24. Epub 2021 May 24.

M. Tian, Z. Wu, J. Heng, F. Chen, W. Guan, and S. Zhang are with the Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China. F. Chen, W. Guan, and S. Zhang are with the College of Animal Science and National Engineering Research Center for Breeding Swine Industry, and the Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.

Diabetes, obesity, and other metabolic diseases have been recognized as the main factors that endanger human health worldwide. Most of these metabolic syndromes develop when the energy balance in the body is disrupted. Energy balance depends upon the systemic regulation of food intake, glucose homeostasis, and lipid metabolism. Fatty acid-binding G protein-coupled receptors (GPCRs) are widely expressed in various types of tissues and cells involved in energy homeostasis regulation. In this review, the distribution and biological functions of fatty acid-binding GPCRs are summarized, particularly with respect to the gut, pancreas, and adipose tissue. A systematic understanding of the physiological functions of the fatty acid-binding GPCRs involved in energy homeostasis regulation will help in identifying novel pharmacological targets for metabolic diseases.
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http://dx.doi.org/10.1093/nutrit/nuab021DOI Listing
May 2021

Low-intensity pulsed ultrasound enhances angiogenesis in rabbit capsule tissue that acts as a novel vascular bed in vivo.

Adv Clin Exp Med 2021 May 18. Epub 2021 May 18.

Department of Urology, Shanghai Children's Hospital, Shanghai Jiao Tong University, China.

Background: In vivo prevascularization followed by pedicled transfer has emerged as a promising strategy for tissue engineering in recent years. We recently demonstrated that capsule tissue could serve as a novel axial in vivo vascular bed, although its high-density microvessels could only be maintained for about a week.

Objectives: In this present study, we aimed to demonstrate whether low-intensity pulsed ultrasound (LIPUS) promotes angiogenesis in capsule tissue.

Material And Methods: After successful induction of capsule tissue using a skin expander, 24 rabbits were randomly divided into the LIPUS group and the control group. The LIPUS group received LIPUS treatment 3 times per week. After 2 and 4 weeks of treatment, angiogenesis of the capsule tissue was assessed using in vivo and in vitro methods, including contrast-enhanced ultrasound (CEUS), photoacoustic imaging (PAI), photoacoustic microscope (PAM), and CD31 immunohistochemistry.

Results: In vivo assessments (CEUS, PAI and PAM) showed that tissue perfusion, hemoglobin content and vascular density were all significantly higher in the LIPUS group, which was consistent with CD31 immunohistochemistry. The LIPUS also promoted protein and mRNA expression of vascular endothelial growth factor α (VEGFα) and basic fibroblast growth factor (bFGF) in capsule tissue. Furthermore, cell experiments showed that LIPUS enhanced tube formation of human microvascular endothelial cells (HMECs) and promoted secretion of VEGFα and bFGF.

Conclusions: The LIPUS treatment promoted angiogenesis of the capsule tissue by stimulating release of angiogenic factors such as VEGFα and bFGF from endothelial cells, making the capsule tissue more potent and sustained when acting as in vivo vascular bed.
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http://dx.doi.org/10.17219/acem/134115DOI Listing
May 2021

Conductive property of secondary minerals triggered Cr(VI) bioreduction by dissimilatory iron reducing bacteria.

Environ Pollut 2021 Apr 24;286:117227. Epub 2021 Apr 24.

School of Minerals Processing and Bioengineering, Key Laboratory of Biohydrometallurgy of Ministry of Education, Central South University, Changsha, 410083, China. Electronic address:

Although secondary minerals have great potential for heavy metal removal, their impact on chromium biogeochemistry in subsurface environments associated with dissimilatory iron reducing bacteria (DIRB) remains poorly characterized. Here, we have investigated the mechanisms of biogenic secondary minerals on the rate of Cr(VI) bioreduction with shewanella oneidensis MR-1. Batch results showed that the biogenic secondary minerals, schwertmannite and jarosite, appreciably increased the Cr(VI) bioreduction rate. UV-vis diffuse reflection spectra showed that schwertmannite and jarosite are semiconductive minerals, which can be activated by MR-1, followed by transferred conduction electrons toward Cr(VI). Cyclic voltammetry and Tafel analysis suggested that the resistance of secondary minerals is a dominant factor controlling Cr(VI) bioreduction. In addition, Cr(VI) adsorption on secondary minerals through ligand exchange promoted Cr(VI) bioreduction by decreasing the electron transfer distance between MR-1 and chromate. Fe(III)/Fe(II) cycling in schwertmannite and jarosite also contributed to Cr(VI) bioreduction as reflected by X-ray photoelectron spectroscopy and Fourier transform infrared spectrometer. Complementary characterizations further verified the contributions of Fe(III)/Fe(II) cycling, Cr(VI) adsorption, and conduction band electron transfer to enhanced Cr(VI) bioreduction. This study provides new insights on the understanding of Cr(VI) bioreduction by semiconductor minerals containing sulfate in subsurface environments.
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http://dx.doi.org/10.1016/j.envpol.2021.117227DOI Listing
April 2021

The effects of infliximab in treating idiopathic inflammatory myopathies: A review article.

Dermatol Ther 2021 May 14:e14976. Epub 2021 May 14.

Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

Anti-TNF treatment may be useful for patients with idiopathic inflammatory myopathies (IIMs). The purpose of this study is to assess the efficacy of infliximab (IFX) in the management of IIMs. Two databases (ie, PubMed and China National Knowledge Infrastructure) were searched up to Nov 2020 for studies investigating skin lesions and muscular weakness in patients with IIMs treated with IFX. A total of 18 studies were included. One hundred and eighteen patients were identified, including 58 adult patients and 60 patients with juvenile dermatomyositis (JDM) treated with IFX. Among these patients, 110 (93%) patients with refractory cases. In addition to glucocorticoids, patients from 15/18 studies received immunosuppressant agents (ISAs) concomitantly with IFX, among which methotrexate (MTX) was most common. After treatment with IFX, skin lesions and muscle strength were improved in 67% of patients with DM and 75% of patients with JDM, respectively. Skin calcinosis was improved in 21/34 (62%) of patients with JDM. Only 55% (12/22) of patients with polymyositis exhibited improvements in muscle strength. Lastly, 40% (42/104) of patients reported adverse events. Current evidence appears to support the use of IFX in some patients with refractory IIMs, especially those with JDM. The most common adverse reaction was infection. Large, randomized-controlled studies should be carried out to confirm these findings.
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http://dx.doi.org/10.1111/dth.14976DOI Listing
May 2021

Association of gestational diabetes mellitus with changes in gut microbiota composition at the species level.

BMC Microbiol 2021 May 14;21(1):147. Epub 2021 May 14.

Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Gestational diabetes mellitus (GDM), a common endocrine disorder with rising prevalence in pregnancy, has been reported to be associated with alteration of gut microbiota in recent years. However, the role of gut microbiome in GDM physiopathology remains unclear. This pilot study aims to characterize the alteration of gut microbiota in GDM on species-level resolution and evaluate the relationship with occurrence of GDM.

Methods: An analysis based on 16S rRNA microarray was performed on fecal samples obtained from 30 women with GDM and 28 healthy pregnant women.

Results: We found 54 and 141 differentially abundant taxa between GDM and control group at the genus and the species level respectively. Among GDM patients, Peptostreptococcus anaerobius was inversely correlated with fasting glucose while certain species (e.g., Aureimonas altamirensis, Kosakonia cowanii) were positively correlated with fasting glucose.

Conclusions: This study suggests that there are large amounts of differentially abundant taxa between GDM and control group at the genus and the species level. Some of these taxa were correlated with blood glucose level and might be used as biomarkers for diagnoses and therapeutic targets for probiotics or synbiotics.
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http://dx.doi.org/10.1186/s12866-021-02207-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122539PMC
May 2021

Epidemiological and clinical features of SARS-CoV-2 cluster infection in Anhui Province, Eastern China.

Int J Infect Dis 2021 May 10. Epub 2021 May 10.

Anhui Provincial Center for Disease Control and Prevention, Hefei, China. Electronic address:

Background: COVID-19 has spread worldwide and become a pandemic. We report the epidemiological and clinical characteristics of cluster infections.

Methods: Data of clustered cases were retrieved from the public health emergency monitoring information system of China. We analyzed the incubation period, generation gap, secondary attack rate, and viral load in various grouped cases.

Results: A total of 60 COVID-19 infection clusters including 226 patients and 19 asymptomatic cases involving four generations were analyzed. With the increase of transmission generations, secondary attack rate decreased (P<0.001) and severity alleviated (P = 0.008). The median incubation period and intergenerational interval were 9 and 6 days, respectively. The secondary attack rate was 7.1% in the index cases, 5.0% in the first generation, 1.0% in the second generation, and 4.7% overall. Severe cases were seen more in the index (13, 65%) and first generation (7, 35%) ones, who had a significantly higher viral load than the mild and moderate ones.

Conclusions: With the increase of transmission generation, secondary infection rate and severity decreased. Severe patients had a higher virus load. Patients in the incubation period and asymptomatic carriers were potential infection sources who might play an important role in transmission.
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http://dx.doi.org/10.1016/j.ijid.2021.04.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110625PMC
May 2021

Pixel dislocation correction method for a laser confocal scanning microscope through the nonlinear triangular wave driving mode and square wave index reconstruction.

Appl Opt 2021 Apr;60(12):3492-3500

The reciprocate scanning scheme of two-dimensional galvanometers is widely used in laser confocal scanning microscopes with high speed. However, the equal interval acquisition of an analog digital acquisition card (AD) and the unequal change of the galvanometer's scanning speed will cause the dislocation of pixels and distortion of the reconstructed image. Meanwhile, the movement properties of the galvanometers in the edge of the scanning area are complex, which will increase the difficulty of segmenting the collected one-dimensional data stream the AD collected into row data of a two-dimensional reconstructed image. Therefore, how to timely and accurately segment the one-dimensional data stream the AD collected into the row data of two-dimensional reconstructed image is not only the key to solve image distortion of a laser confocal scanning microscope with high speed but also the prerequisite to improve the accuracy of row data dislocation correction. A driving mode based on the nonlinear triangular wave and a dislocation-correcting method using a square wave index are proposed. Namely, on the basis of the galvanometer's scanning analysis, the equation of a nonlinear triangular wave driving voltage is established, and the switching frequency of the Y-galvanometer's driving voltage is obtained by calculating the collected switching frequency of the X-galvanometer; thus, the uniformity of the galvanometer's scanning trajectories is secured. Finally, the row segmentation flag pulse is first introduced into the one-dimensional data stream the AD collected, and the square wave index is used to segment the collected data, which means the one-dimensional data stream can be segmented timely and accurately via hardware method. Meanwhile, the pixel dislocation can be corrected. The experimental result shows that, compared with the Nikon A1R+ confocal microscope, the proposed method can effectively correct the pixel dislocation, and the position coincidence error is less than 0.7%. The proposed method will be helpful to improve the image quality of a laser confocal scanning microscope with high speed.
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http://dx.doi.org/10.1364/AO.420889DOI Listing
April 2021

PAL-mediated SA biosynthesis pathway contributes to nematode resistance in wheat.

Plant J 2021 May 11. Epub 2021 May 11.

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, China.

The pathogen cereal cyst nematode (CCN) is deleterious to Triticeae crops and is a threat to the global crop yield. Accession no. 1 of Aegilops variabilis, a relative of Triticum aestivum (bread wheat), is highly resistant to CCN. Our previous study demonstrated that the expression of the phenylalanine ammonia lyase (PAL) gene AevPAL1 in Ae. variabilis is strongly induced by CCN. PAL, the first enzyme of phenylpropanoid metabolism, is involved in abiotic and biotic stress responses. However, its role in plant-CCN interaction remains unknown. In the present study, we proved that AevPAL1 helps to confer CCN resistance through affecting the synthesis of salicylic acid (SA) and downstream secondary metabolites. The silencing of AevPAL1 increased the incidence of CCN infection in roots and decreased the accumulation of SA and phenylalanine (Phe)-derived specialized metabolites. The exogenous pre-application of SA also improved CCN resistance. Additionally, the functions of PAL in phenylpropanoid metabolism correlated with tryptophan decarboxylase (TDC) functioning in tryptophan metabolism pathways. The silencing of either AevPAL1 or AevTDC1 exhibited a concomitant reduction in the expression of both genes and the contents of metabolites downstream of PAL and TDC. These results suggested that AevPAL1, possibly in coordination with AevTDC1, positively contributes to CCN resistance by altering the downstream secondary metabolites and SA content in Ae. variabilis. Moreover, AevPAL1 overexpression significantly enhanced CCN resistance in bread wheat and did not exhibit significant negative effects on yield-related traits, suggesting that AevPAL1 is valuable for the genetic improvement of CCN resistance in bread wheat.
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http://dx.doi.org/10.1111/tpj.15316DOI Listing
May 2021

Primary malignant teratoma of the kidney: a rare case report and literature review.

Transl Androl Urol 2021 Apr;10(4):1807-1812

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

Teratomas originate from pluripotent cells and can differentiate along one or more embryonic germ lines. Renal teratoma is infrequent and malignant renal teratoma is even rarer. Experience in the diagnosis and treatment of this uncommon malignancy is seriously limited. In this report, we described the case of a 64-year-old female who complained of right flank pain for 4 months. Computed tomography (CT) revealed a hypodense mass (50 mm in maximum diameter) with slow contrast enhancement and obscure boundary located in the lower pole of the right kidney. CT also showed multiple retroperitoneal lymphadenectasis. Retroperitoneal laparoscopic right radical nephrectomy along with regional lymphadenectomy was successfully performed, and postoperative pathological examination confirmed malignant teratoma of the kidney. After surgery, the patient received adjuvant chemotherapy with BEP (bleomycin, etoposide, and cisplatin) protocol. At the 6-month follow-up, pulmonary and liver metastases were discovered by CT and the patient refused any further treatment. Unfortunately, she died at 16 months postoperatively. Although primary renal malignant teratoma is extremely rare, this kind of tumor should be taken into consideration. Currently, there is no therapeutic standard consensus for this disease and the prognosis remains unclear. Early detection and surgical intervention is critical, and more research on postoperative adjuvant therapy should be performed.
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http://dx.doi.org/10.21037/tau-21-97DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100854PMC
April 2021

Exceptional Cocatalyst-Free Photo-Enhanced Piezocatalytic Hydrogen Evolution of Carbon Nitride Nanosheets from Strong In-Plane Polarization.

Adv Mater 2021 May 8:e2101751. Epub 2021 May 8.

Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid Wastes, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing, 100083, China.

Utilizing mechanical energy to produce hydrogen is emerging as a promising way to generate renewable energy, but is challenged by low efficiency and scanty cognition. In this work, graphitic carbon nitride (g-C N ) with an atomically thin sheet-like structure is applied for prominent piezocatalytic and photo-enhanced piezocatalytic H production. It is revealed that the anomalous piezoelectricity in g-C N originates from the strong in-plane polarization along the a-axis, contributed by the superimposed polar tri-s-triazine units and flexoelectric effect derived from the structured triangular cavities, which provides powerful electrochemical driving force for the water reduction reaction. Furthermore, the photo-enhanced charge transfer enables g-C N nanosheets to reserve more energized polarization charges to fully participate in the reaction at the surface reactive sites enriched by strain-induced carbon vacancies. Without any cocatalysts, an exceptional photo-piezocatalytic H evolution rate of 12.16 mmol g h is delivered by the g-C N nanosheets, far exceeding that of previously reported piezocatalysts and g-C N photocatalysts. Further, high pure-water-splitting performance with production of the value-added oxidation product H O via photo-piezocatalysis is also disclosed. This work not only exposes the potential of g-C N as a piezo-semiconductor for catalytic H evolution, but also breaks a new ground for the conversion of solar and mechanical energy by photomediated piezocatalytic reaction.
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http://dx.doi.org/10.1002/adma.202101751DOI Listing
May 2021

Frequency and phenotypic characteristics of RPE65 mutations in the Chinese population.

Orphanet J Rare Dis 2021 Apr 13;16(1):174. Epub 2021 Apr 13.

Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, 200032, China.

Background: The retinoid isomerohydrolase RPE65 has received considerable attention worldwide since a successful clinical gene therapy was approved in 2017 as the first treatment for vision loss associated with RPE65-mediated inherited retinal disease. Identifying patients with RPE65 mutations is a prerequisite to assessing the patients' eligibility to receive RPE65-targeted gene therapies, and it is necessary to identify individuals who are most likely to benefit from gene therapies. This study aimed to investigate the RPE65 mutations frequency in the Chinese population and to determine the genetic and clinical characteristics of these patients.

Results: Only 20 patients with RPE65 mutations were identified, and RPE65 mutations were determined to be the 14th most common among all patients with genetic diagnoses. Ten novel variants and two hotspots associated with FAP were identified. A literature review revealed that a total of 57 patients of Chinese origin were identified with pathogenic mutations in the RPE65 gene. The mean best Snellen corrected visual acuity was worse (mean 1.3 ± 1.3 LogMAR) in patients older than 20 years old than in those younger than 15 years old (0.68 ± 0.92 LogMAR). Bone spicule-like pigment deposits (BSLPs) were observed in six patients; they were older than those without BSLP and those with white-yellow dots. Genotype-phenotype analysis revealed that truncating variants seem to lead to a more severe clinical presentation, while best corrected visual acuity testing and fundus changes did not correlate with specific RPE65 variants or mutation types.

Conclusions: This study provides a detailed clinical-genetic assessment of patients with RPE65 mutations of Chinese origin. These results may help to elucidate RPE65 mutations in the Chinese population and may facilitate genetic counseling and the implementation of gene therapy in China.
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http://dx.doi.org/10.1186/s13023-021-01807-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097799PMC
April 2021

Classification of non-acute bronchial asthma according to allergy and eosinophil characteristics: a retrospective study.

Allergy Asthma Clin Immunol 2021 May 3;17(1):45. Epub 2021 May 3.

Department of Respiratory and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

Background: Investigating the endotypes of the different asthma phenotypes would help disease monitoring, prognosis determination, and improving asthma management standardization. This study aimed to classify asthma into four endotypes according to the allergic and eosinophilic characteristics and explore the phenotypes (clinical characteristics, pulmonary functions, and fractional expired nitric oxide (FeNO)) of each endotype.

Methods: This retrospective study included non-acute asthma patients treated at the First Hospital of Shanxi Medical University (05/2016-01/2018). The patients were classified into the eosinophilic allergic, eosinophilic non-allergic, non-eosinophilic allergic, and non-eosinophilic non-allergic asthma endotypes. Serum sIgE, lung function, FeNO, and induced sputum cytology were tested and compared among groups.

Results: Of the 171 included patients, 22 had eosinophilic allergic asthma, 17 had eosinophilic non-allergic asthma, 66 had non-eosinophilic allergic asthma, and 66 had non-eosinophilic non-allergic asthma. Lung function measurements (FEV1%, FEF25%, FEF50%, FEF75%, and FEF25-75%) showed that airway dysfunction was worse in eosinophilic non-allergic asthma than in the other three endotypes (all P < 0.001). In allergic asthma patients, eosinophilic asthma had worse airway dysfunction than non-eosinophilic asthma (all P < 0.05). Similar results were found in non-allergic asthma (all P < 0.01). The FeNO levels in eosinophilic allergic asthma were higher than in eosinophilic non-allergic and non-eosinophilic non-allergic asthma (both P = 0.001).

Conclusions: FeNO can objectively reflect eosinophilic airway inflammation in asthma. Endotypic classification of asthma patients regarding the allergic and eosinophilic characteristics is conducive to the effective management of patients with asthma.
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http://dx.doi.org/10.1186/s13223-021-00546-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091754PMC
May 2021