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1.
Article in Chinese | MEDLINE | ID: mdl-38965849

ABSTRACT

Objective: To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis. Methods: The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software. Results: Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP. Conclusion: The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.


Subject(s)
Nasal Polyps , Phenotype , Sinusitis , Humans , Nasal Polyps/complications , Male , Female , Sinusitis/complications , Middle Aged , Adult , Chronic Disease , Adolescent , Aged , Cluster Analysis , Young Adult , Child , Aged, 80 and over , Eosinophils , Rhinitis/complications , Immunoglobulin E/blood , Asthma/complications , Neutrophils/metabolism , Rhinosinusitis
4.
BMC Womens Health ; 24(1): 386, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38961373

ABSTRACT

BACKGROUND: Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV. METHODS: This retrospective case-control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann-Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve. RESULTS: The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717-0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578-0.697), 0.71 (95% confidence interval: 0.656-0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862-0.927) with sensitivity of 88.9% and specificity of 77.7%. CONCLUSION: In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.


Subject(s)
Endometriosis , Fibrinogen , Neutrophils , Humans , Female , Endometriosis/blood , Endometriosis/complications , Endometriosis/diagnosis , Adult , Retrospective Studies , Case-Control Studies , Fibrinogen/analysis , Partial Thromboplastin Time , Blood Coagulation/physiology , Severity of Illness Index , CA-125 Antigen/blood , ROC Curve , Lymphocytes , Biomarkers/blood
5.
BMC Pulm Med ; 24(1): 312, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961438

ABSTRACT

BACKGROUND: The Omicron variant broke out in China at the end of 2022, causing a considerable number of severe cases and even deaths. The study aimed to identify risk factors for death in patients hospitalized with SARS-CoV-2 Omicron infection and to establish a scoring system for predicting mortality. METHODS: 1817 patients were enrolled at eight hospitals in China from December 2022 to May 2023, including 815 patients in the training group and 1002 patients in the validation group. Forty-six clinical and laboratory features were screened using LASSO regression and multivariable logistic regression. RESULTS: In the training set, 730 patients were discharged and 85 patients died. In the validation set, 918 patients were discharged and 84 patients died. LASSO regression identified age, levels of interleukin (IL) -6, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and D-dimer; neutrophil count, neutrophil-to-lymphocyte ratio (NLR) as associated with mortality. Multivariable logistic regression analysis showed that older age, IL-6, BUN, LDH and D-dimer were significant independent risk factors. Based on these variables, a scoring system was developed with a sensitivity of 83.6% and a specificity of 83.5% in the training group, and a sensitivity of 79.8% and a sensitivity of 83.0% in the validation group. CONCLUSIONS: A scoring system based on age, IL-6, BUN, LDH and D-dime can help clinicians identify patients with poor prognosis early.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/mortality , Male , Female , Middle Aged , China/epidemiology , Aged , Risk Factors , Hospitalization/statistics & numerical data , Adult , Prognosis , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/metabolism , Age Factors , Logistic Models , Neutrophils , Blood Urea Nitrogen , L-Lactate Dehydrogenase/blood
6.
Front Immunol ; 15: 1406794, 2024.
Article in English | MEDLINE | ID: mdl-38953030

ABSTRACT

Introduction: Equine asthma (EA) is a common lower airway disease in horses, but whether its pathogenesis is allergic is ambiguous. Extrinsic stimuli like hay dust induce acute exacerbation of clinical signs and sustained local neutrophilic inflammation in susceptible horses. Aspergillus fumigatus is an EA stimulus, but it is unclear if it merely acts as an IgE-provoking allergen. We aimed to comprehensively analyze immunoglobulin (Ig) isotypes in EA, elucidating their binding to different A. fumigatus antigens, and their quantities systemically in serum and locally in bronchoalveolar lavage fluid (BALF). Methods: Serum and BALF from healthy horses (HE, n = 18) and horses with mild-moderate asthma (MEA, n = 20) or severe asthma (SEA, n = 24) were compared. Ig isotype (IgG1, IgG3/5, IgG4/7, IgG6, IgA, and IgE) binding to nine antigens (A. fumigatus lysate, and recombinant Asp f 1, Asp f 7, Asp f 8, dipeptidyl-peptidase 5, class II aldolase/adducin domain protein, glucoamylase, beta-hexosaminidase, and peptide hydrolase) was compared by enzyme-linked immunosorbent assays. Total Ig isotype contents were determined by bead-based assays. Results: MEA and SEA differed from HE but hardly from each other. Compared to HE, asthmatic horses showed increased anti-A. fumigatus binding of IgG (BALF and serum) and IgA (BALF). Serum and BALF IgE binding and total IgE contents were similar between HE and EA. Single antigens, as well as A. fumigatus lysate, yielded similar Ig binding patterns. Serum and BALF IgG1 binding to all antigens was increased in SEA and to several antigens in MEA. Serum IgG4/7 binding to two antigens was increased in SEA. BALF IgA binding to all antigens was increased in SEA and MEA. Total BALF IgG1 and IgG4/7 contents were increased in SEA, and serum IgG4/7 content was increased in MEA compared to HE. Yet, total isotype contents differentiated EA and HE less clearly than antigen-binding Ig. Discussion: A. fumigatus immunogenicity was confirmed without identification of single dominant antigens here. A. fumigatus provoked elevated BALF IgG1 and IgA binding, and these isotypes appear relevant for neutrophilic EA, which does not support allergy. BALF Ig isotype differentiation beyond IgE is crucial for a comprehensive analysis of immune responses to fungi in EA pathogenesis.


Subject(s)
Antigens, Fungal , Aspergillus fumigatus , Asthma , Bronchoalveolar Lavage Fluid , Horse Diseases , Immunoglobulin A , Immunoglobulin G , Animals , Horses/immunology , Aspergillus fumigatus/immunology , Bronchoalveolar Lavage Fluid/immunology , Asthma/immunology , Asthma/microbiology , Immunoglobulin G/immunology , Immunoglobulin G/blood , Immunoglobulin A/immunology , Immunoglobulin A/blood , Immunoglobulin A/metabolism , Horse Diseases/immunology , Horse Diseases/microbiology , Antigens, Fungal/immunology , Male , Neutrophils/immunology , Neutrophils/metabolism , Female , Immunoglobulin E/immunology , Immunoglobulin E/blood , Antibodies, Fungal/immunology , Antibodies, Fungal/blood
7.
Methods Mol Biol ; 2814: 195-207, 2024.
Article in English | MEDLINE | ID: mdl-38954207

ABSTRACT

Activation of G protein-coupled receptors upon chemoattractant stimulation induces activation of multiple signaling pathways. To fully understand how these signaling pathway coordinates to achieve directional migration of neutrophils, it is essential to determine the dynamics of the spatiotemporal activation profile of signaling components at the level of single living cells. Here, we describe a detailed methodology for monitoring and quantitatively analyzing the spatiotemporal dynamics of 1,4,5-inositol trisphosphate (IP3) in neutrophil-like HL60 cells in response to various chemoattractant fields by applying Förster resonance energy transfer (FRET) fluorescence microscopy.


Subject(s)
Fluorescence Resonance Energy Transfer , Inositol 1,4,5-Trisphosphate , Microscopy, Confocal , Microscopy, Fluorescence , Receptors, G-Protein-Coupled , Humans , Receptors, G-Protein-Coupled/metabolism , Fluorescence Resonance Energy Transfer/methods , HL-60 Cells , Microscopy, Fluorescence/methods , Microscopy, Confocal/methods , Inositol 1,4,5-Trisphosphate/metabolism , Signal Transduction , Neutrophils/metabolism
8.
J Biomed Sci ; 31(1): 66, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951890

ABSTRACT

BACKGROUND: Cholestasis is a common yet severe complication that occurs during the advancement of liver metastasis. However, how cholestasis impacts the development, treatment, and tumor microenvironment (TME) of liver metastasis remains to be elucidated. METHODS: Extrahepatic and intrahepatic cholestatic mouse models with liver metastasis were established to detect the differential expression levels of genes, infiltration of immune cells and change in bile acid-associated metabolites by using RNA-Sequencing, flowcytometry, and liquid chromatography and mass spectrometry. Western blot was applied to neutrophils under the stimulation of primary bile acids (BAs) in vitro to study the mechanism of phenotypic alteration. In vitro coculture of BA-treated neutrophils with CD8+ T cells were performed to study the immune-suppressive effect of phenotypic-altered neutrophils. Clinical samples collected from colorectal cancer patients with liver metastasis and cholestasis were applied to RNA-Seq. RESULTS: Compared to non-cholestatic mice, the progression of liver metastasis of cholestatic mice was significantly accelerated, which was associated with increased neutrophil infiltration and T-cell exclusion. Both neutrophils and T cells expressed higher immunosuppressive markers in the cholestatic mouse model, further indicating that an immunosuppressive tumor microenvironment was induced during cholestasis. Although neutrophils deletion via anti-Ly6G antibody partially hindered liver metastasis progression, it reduced the overall survival of mice. Tauro-ß-muricholic acid (Tß-MCA) and Glycocholic acid (GCA), the two most abundant cholestasis-associated primary BAs, remarkably promoted the expression of Arg1 and iNOS on neutrophils via p38 MAPK signaling pathway. In addition, BAs-pretreated neutrophils significantly suppressed the activation and cytotoxic effects of CD8+ T cells, indicating that the immunosuppressive phenotype of neutrophils was directly induced by BAs. Importantly, targeting BA anabolism with Obeticholic acid (OCA) under cholestasis effectively suppressed liver metastasis progression, enhanced the efficacy of immune checkpoint blockade, and prolonged survival of mice. CONCLUSIONS: Our study reveals the TME of cholestasis-associated liver metastasis and proposes a new strategy for such patients by targeting bile acid anabolism.


Subject(s)
Cholestasis , Colorectal Neoplasms , Liver Neoplasms , Neutrophils , Animals , Neutrophils/immunology , Mice , Liver Neoplasms/secondary , Liver Neoplasms/immunology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/immunology , Cholestasis/immunology , Cholestasis/metabolism , Tumor Microenvironment , Male , Mice, Inbred C57BL , Humans , Disease Models, Animal
9.
Elife ; 132024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953882

ABSTRACT

An influx of water molecules can help immune cells called neutrophils to move to where they are needed in the body.


Subject(s)
Neutrophils , Neutrophils/immunology , Humans , Animals , Water
10.
CNS Neurosci Ther ; 30(7): e14825, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38954749

ABSTRACT

AIMS: Ischemic stroke remains a challenge in medical research because of the limited treatment options. Recombinant human tissue plasminogen activator (rtPA) is the primary treatment for recanalization. However, nearly 50% of the patients experience complications that result in ineffective reperfusion. The precise factors contributing to ineffective reperfusion remain unclear; however, recent studies have suggested that immune cells, notably neutrophils, may influence the outcome of rtPA thrombolysis via mechanisms such as the formation of neutrophil extracellular traps. This study aimed to explore the nonthrombolytic effects of rtPA on neutrophils and highlight their contribution to ineffective reperfusion. METHODS: We evaluated the effects of rtPA treatment on middle cerebral artery occlusion in rats. We also assessed neutrophil infiltration and activation after rtPA treatment in vitro and in vivo in a small cohort of patients with massive cerebral ischemia (MCI). RESULTS: rtPA increased neutrophil infiltration into the brain microvessels and worsened blood-brain barrier damage during ischemia. It also increased the neutrophil counts of the patients with MCI. CONCLUSION: Neutrophils play a crucial role in promoting ischemic injury and blood-brain barrier disruption, making them potential therapeutic targets.


Subject(s)
Fibrinolytic Agents , Neutrophils , Recombinant Proteins , Tissue Plasminogen Activator , Tissue Plasminogen Activator/pharmacology , Tissue Plasminogen Activator/therapeutic use , Animals , Humans , Male , Neutrophils/drug effects , Rats , Recombinant Proteins/pharmacology , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/therapeutic use , Infarction, Middle Cerebral Artery/drug therapy , Rats, Sprague-Dawley , Aged , Blood-Brain Barrier/drug effects , Cell Movement/drug effects , Female , Neutrophil Infiltration/drug effects , Middle Aged , Brain Ischemia/drug therapy , Brain Ischemia/immunology , Disease Models, Animal
11.
Cell Death Dis ; 15(7): 479, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965211

ABSTRACT

TLR4 and TNFR1 signalling promotes potent proinflammatory signal transduction events, thus, are often hijacked by pathogenic microorganisms. We recently reported that myeloid cells retaliate Yersinia blockade of TAK1/IKK signalling by triggering RIPK1-dependent caspase-8 activation that promotes downstream GSDMD and GSDME-mediated pyroptosis in macrophages and neutrophils respectively. However, the upstream signalling events for RIPK1 activation in these cells are not well defined. Here, we demonstrate that unlike in macrophages, RIPK1-driven pyroptosis and cytokine priming in neutrophils are driven through TNFR1 signalling, while TLR4-TRIF signalling is dispensable. Furthermore, we demonstrate that activation of RIPK1-dependent pyroptosis in neutrophils during Yersinia infection requires IFN-γ priming, which serves to induce surface TNFR1 expression and amplify soluble TNF secretion. In contrast, macrophages utilise both TNFR1 and TLR4-TRIF signalling to trigger cell death, but only require TRIF but not autocrine TNFR1 for cytokine production. Together, these data highlight the emerging theme of cell type-specific regulation in cell death and immune signalling in myeloid cells.


Subject(s)
Macrophages , Neutrophils , Pyroptosis , Receptor-Interacting Protein Serine-Threonine Kinases , Receptors, Tumor Necrosis Factor, Type I , Signal Transduction , Toll-Like Receptor 4 , Macrophages/metabolism , Neutrophils/metabolism , Animals , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Receptors, Tumor Necrosis Factor, Type I/metabolism , Mice , Toll-Like Receptor 4/metabolism , Adaptor Proteins, Vesicular Transport/metabolism , Mice, Inbred C57BL , Interferon-gamma/metabolism , Mice, Knockout
12.
Sci Rep ; 14(1): 15391, 2024 07 04.
Article in English | MEDLINE | ID: mdl-38965325

ABSTRACT

In this study, We aim to explore the association between the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), lymphocyte to monocyte ratio (LMR) and prognostic nutritional index (PNI) and distant metastasis of gastric cancer and develop an efficient nomogram for screening patients with distant metastasis. A total of 1281 inpatients with gastric cancer were enrolled and divided into the training and validation set.Univariate, Lasso regression and Multivariate Logistic Regression Analysis was used to identify the risk factors of distant metastasis. The independent predictive factors were then enrolled in the nomogram model. The nomogram's predictive perform and clinical practicality was evaluated by receiver operating characteristics (ROC) curves, calibration curves and decision curve analysis. Multivariate Logistic Regression Analysis identified D-dimer, CA199, CA125, NLR and PNI as independent predictive factors. The area under the curve of our nomogram based on these factors was 0.838 in the training cohort and 0.811 in the validation cohort. The calibration plots and decision curves demonstrated the nomogram's good predictive performance and clinical practicality in both training and validation cohort. Therefore,our nomogram could be an important tool for clinicians in screening gastric cancer patients with distant metastasis.


Subject(s)
Lymphocytes , Neutrophils , Nomograms , Nutrition Assessment , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/blood , Male , Female , Neutrophils/pathology , Middle Aged , Lymphocytes/pathology , Prognosis , Aged , ROC Curve , Neoplasm Metastasis , Lymphocyte Count , Risk Factors , Fibrin Fibrinogen Degradation Products/metabolism , Fibrin Fibrinogen Degradation Products/analysis , Adult , CA-125 Antigen/blood , Antigens, Tumor-Associated, Carbohydrate
13.
Neurol Neuroimmunol Neuroinflamm ; 11(5): e200278, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38954781

ABSTRACT

BACKGROUND AND OBJECTIVES: Neutrophils, underestimated in multiple sclerosis (MS), are gaining increased attention for their significant functions in patients with MS and the experimental autoimmune encephalomyelitis (EAE) animal model. However, the precise role of neutrophils in cervical lymph nodes (CLNs), the primary CNS-draining lymph nodes where the autoimmune response is initiated during the progression of EAE, remains poorly understood. METHODS: Applying single-cell RNA sequencing (scRNA-seq), we constructed a comprehensive immune cell atlas of CLNs during development of EAE. Through this atlas, we concentrated on and uncovered the transcriptional landscape, phenotypic and functional heterogeneity of neutrophils, and their crosstalk with immune cells within CLNs in the neuroinflammatory processes in EAE. RESULTS: Notably, we observed a substantial increase in the neutrophil population in EAE mice, with a particular emphasis on the significant rise within the CLNs. Neutrophils in CLNs were categorized into 3 subtypes, and we explored the specific roles and developmental trajectories of each distinct neutrophil subtype. Neutrophils were found to engage in extensive interactions with other immune cells, playing crucial roles in T-cell activation. Moreover, our findings highlighted the strong migratory ability of neutrophils to CLNs, partly regulated by triggering the receptor expressed on myeloid cells 1 (TREM-1). Inhibiting TREM1 with LR12 prevents neutrophil migration both in vivo and in vitro. In addition, in patients with MS, we confirmed an increase in peripheral neutrophils with an upregulation of TREM-1. DISCUSSION: Our research provides a comprehensive and precise single-cell atlas of CLNs in EAE, highlighting the role of neutrophils in regulating the periphery immune response. In addition, TREM-1 emerged as an essential regulator of neutrophil migration to CLNs, holding promise as a potential therapeutic target in MS.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Mice, Inbred C57BL , Neutrophils , Single-Cell Analysis , Triggering Receptor Expressed on Myeloid Cells-1 , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Encephalomyelitis, Autoimmune, Experimental/genetics , Neutrophils/metabolism , Neutrophils/immunology , Animals , Triggering Receptor Expressed on Myeloid Cells-1/metabolism , Mice , Female , Sequence Analysis, RNA , Lymph Nodes/metabolism
14.
Sci Rep ; 14(1): 15232, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956281

ABSTRACT

Intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) was associated with coronary artery lesions. Neutrophil percentage-to-albumin ratio (NPAR) is an index of mortality in several inflammatory diseases. This study focused on the association of NPAR with IVIG- resistance in KD. Clinical and laboratory data of 438 children with KD before IVIG treatment were retrospectively analyzed. Notably, high NPAR was associated with older age, high WBC, NP, ALT, total bilirubin and CRP, as well as with high the incidence of IVIG-resistance, and with low hemoglobin (Hb), PLT, ALB and sodium levels. NPAR (OR: 2.366, 95% CI: 1.46-3.897, p = 0.001) and Hb (OR: 0.967, 95% CI: 0.944-0.989, p = 0.004) were independent risk factors for IVIG-resistance. NPAR showed linear relation with IVIG-resistance (p for nonlinear = 0.711) and the nonlinear correlation was found between IVIG-resistance and Hb (p for nonlinear = 0.002). The predictive performance of NPAR was superior to Beijing model (z = 2.193, p = 0.028), and not inferior to Chongqing model (z = 0.983, p = 0.326) and the combination of NPAR and Hb (z = 1.912, p = 0.056). These findings revealed that NPAR is a reliable predictor of IVIG-resistance.


Subject(s)
Biomarkers , Drug Resistance , Immunoglobulins, Intravenous , Mucocutaneous Lymph Node Syndrome , Neutrophils , Humans , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/drug therapy , Immunoglobulins, Intravenous/therapeutic use , Male , Female , Child, Preschool , Infant , Biomarkers/blood , Retrospective Studies , Child , Albumins/metabolism
15.
Nat Commun ; 15(1): 5557, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956415

ABSTRACT

Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.


Subject(s)
DNA , Extracellular Traps , Hemostasis , Hemostatics , Hydrogels , Wound Healing , Animals , Extracellular Traps/metabolism , Extracellular Traps/drug effects , DNA/chemistry , Male , Hydrogels/chemistry , Hydrogels/pharmacology , Rats , Hemostasis/drug effects , Wound Healing/drug effects , Hemostatics/pharmacology , Hemostatics/chemistry , Rats, Sprague-Dawley , Hemorrhage , Humans , Neutrophils/metabolism , Disease Models, Animal
16.
Sci Rep ; 14(1): 15075, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956445

ABSTRACT

Sepsis is a severe disease characterized by high mortality rates. Our aim was to develop an early prognostic indicator of adverse outcomes in sepsis, utilizing easily accessible routine blood tests. A retrospective analysis of sepsis patients from the MIMIC-IV database was conducted. We performed univariate and multivariate regression analyses to identify independent risk factors associated with in-hospital mortality within 28 days. Logistic regression was utilized to combine the neutrophil-to-lymphocyte ratio (NLR) and the neutrophil-to-platelet ratio (NPR) into a composite score, denoted as NLR_NPR. We used ROC curves to compare the prognostic performance of the models and Kaplan-Meier survival curves to assess the 28 day survival rate. Subgroup analysis was performed to evaluate the applicability of NLR_NPR in different subpopulations based on specific characteristics. This study included a total of 1263 sepsis patients, of whom 179 died within 28 days of hospitalization, while 1084 survived beyond 28 days. Multivariate regression analysis identified age, respiratory rate, neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-platelet ratio (NPR), hypertension, and sequential organ failure assessment (SOFA) score as independent risk factors for 28 day mortality in septic patients (P < 0.05). Additionally, in the prediction model based on blood cell-related parameters, the combined NLR_NPR score exhibited the highest predictive value for 28 day mortality (AUC = 0.6666), followed by NLR (AUC = 0.6456) and NPR (AUC = 0.6284). Importantly, the performance of the NLR_NPR score was superior to that of the commonly used SOFA score (AUC = 0.5613). Subgroup analysis showed that NLR_NPR remained an independent risk factor for 28 day in-hospital mortality in the subgroups of age, respiratory rate, and SOFA, although not in the hypertension subgroup. The combined use of NLR and NPR from routine blood tests represents a readily available and reliable predictive marker for 28 day mortality in sepsis patients. These results imply that clinicians should prioritize patients with higher NLR_NPR scores for closer monitoring to reduce mortality rates.


Subject(s)
Blood Platelets , Hospital Mortality , Lymphocytes , Neutrophils , Sepsis , Humans , Sepsis/blood , Sepsis/mortality , Sepsis/diagnosis , Male , Female , Prognosis , Aged , Middle Aged , Retrospective Studies , Blood Platelets/pathology , ROC Curve , Risk Factors , Platelet Count , Lymphocyte Count , Aged, 80 and over
17.
J Transl Med ; 22(1): 612, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956669

ABSTRACT

BACKGROUND: Programmed cell death (PCD) has recently been implicated in modulating the removal of neutrophils recruited in acute myocardial infarction (AMI). Nonetheless, the clinical significance and biological mechanism of neutrophil-related PCD remain unexplored. METHODS: We employed an integrative machine learning-based computational framework to generate a predictive neutrophil-derived PCD signature (NPCDS) within five independent microarray cohorts from the peripheral blood of AMI patients. Non-negative matrix factorization was leveraged to develop an NPCDS-based AMI subtype. To elucidate the biological mechanism underlying NPCDS, we implemented single-cell transcriptomics on Cd45+ cells isolated from the murine heart of experimental AMI. We finally conducted a Mendelian randomization (MR) study and molecular docking to investigate the therapeutic value of NPCDS on AMI. RESULTS: We reported the robust and superior performance of NPCDS in AMI prediction, which contributed to an optimal combination of random forest and stepwise regression fitted on nine neutrophil-related PCD genes (MDM2, PTK2B, MYH9, IVNS1ABP, MAPK14, GNS, MYD88, TLR2, CFLAR). Two divergent NPCDS-based subtypes of AMI were revealed, in which subtype 1 was characterized as inflammation-activated with more vibrant neutrophil activities, whereas subtype 2 demonstrated the opposite. Mechanically, we unveiled the expression dynamics of NPCDS to regulate neutrophil transformation from a pro-inflammatory phase to an anti-inflammatory phase in AMI. We uncovered a significant causal association between genetic predisposition towards MDM2 expression and the risk of AMI. We also found that lidoflazine, isotetrandrine, and cepharanthine could stably target MDM2. CONCLUSION: Altogether, NPCDS offers significant implications for prediction, stratification, and therapeutic management for AMI.


Subject(s)
Apoptosis , Myocardial Infarction , Neutrophils , Myocardial Infarction/genetics , Myocardial Infarction/blood , Humans , Neutrophils/metabolism , Animals , Apoptosis/genetics , Machine Learning , Molecular Docking Simulation , Mice, Inbred C57BL , Transcriptome/genetics , Mice , Male
18.
Arch Esp Urol ; 77(5): 498-504, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38982778

ABSTRACT

OBJECTIVE: This study aimed to analyse the value of procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting postoperative ureteral stone complications of urogenic sepsis. The production of a clinical prediction model could provide additional direction to reduce the likelihood of postoperative urogenital sepsis. METHODS: The clinical data of 520 patients with ureteral stones who underwent surgical treatment from January 2022, to September 2023, in the hospital were retrospectively analysed. The patients were divided into urogenic sepsis group (n = 42) and non-urogenic sepsis group (n = 478) in accordance with the occurrence of urogenic sepsis in the postoperative period. The peripheral blood PCT, PLR and NLR levels were collected within 24 h postoperatively in the two groups. The receiver operating characteristic (ROC) curve was employed to evaluate the predictive value of PCT, PLR and NLR levels for postoperative urogenital sepsis in patients with ureteral stones. RESULTS: Logistic regression analysis showed that PCT (odds ratio (OR) = 4.25, 95% CI: 1.85-9.78), PLR (OR = 4.00, 95% CI: 1.78-9.05) and NLR (OR = 2.29, 95% CI: 1.05-5.01) were risk factors for postoperative complication sepsis in patients with ureteral stones (p < 0.05). The ROC curves showed that the areas under the curve of PCT, PLR and NLR levels alone and in combination for predicting urogenic sepsis complications after emergency ureteral stone surgery were 0.683, 0.692, 0.611 and 0.799, respectively. CONCLUSIONS: Urogenic sepsis leads to increased serum PCT, NLR and PLR levels in patients undergoing surgical treatment for ureteral stones. Physicians should pay close attention to these indices to provide further theoretical support for reducing postoperative urogenic sepsis.


Subject(s)
Postoperative Complications , Predictive Value of Tests , Procalcitonin , Sepsis , Ureteral Calculi , Humans , Retrospective Studies , Sepsis/etiology , Sepsis/blood , Ureteral Calculi/surgery , Male , Female , Middle Aged , Postoperative Complications/blood , Postoperative Complications/etiology , Postoperative Complications/diagnosis , Procalcitonin/blood , Neutrophils , Platelet Count , Adult , Cohort Studies , Lymphocyte Count , Aged , Lymphocytes , Leukocyte Count
19.
Chirurgia (Bucur) ; 119(3): 284-293, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38982906

ABSTRACT

Background: This study evaluates the predictive value of preoperative inflammatory markers (NLR, PLR, APRI, SII) and liver function tests in determining the risk of fistula development postcolorectal cancer surgery. The objective was to determine the association between elevated marker levels and fistula risk and establish thresholds for preoperative risk stratification. Methods: A retrospective cohort study was conducted at the "Pius Brinzeu" Clinical Emergency Hospital from 2018 to 2023, analyzing data from 219 patients undergoing colorectal cancer surgery. Results: Among the markers studied, the Systemic Inflammation Index (SII) with a cutoff 460.5 showed the highest sensitivity (75.6%) and specificity (71.3%), resulting in an AUC of 0.774 (p=0.001). Albumin levels 2.9 g/dL also significantly predicted fistula occurrence with 77.3% sensitivity and 73.8% specificity (AUC 0.788, p 0.001). Neutrophil to Lymphocyte Ratio (NLR) and Platelet to Lymphocyte Ratio (PLR) presented cutoffs of 3.95 and 191.6 respectively, demonstrating substantial predictive value with AUCs of 0.732 and 0.746 (p 0.001 and p=0.001, respectively). Conclusions: Elevated levels of specific preoperative inflammatory markers and liver function tests are significantly associated with the risk of developing fistulas in patients undergoing colorectal cancer surgery. These findings support the integration of these biomarkers into preoperative evaluations to enhance patient risk stratification and optimize surgical outcomes, providing a valuable tool for clinical decision-making in colorectal surgery settings.


Subject(s)
Colorectal Neoplasms , Liver Function Tests , Neutrophils , Predictive Value of Tests , Humans , Colorectal Neoplasms/surgery , Colorectal Neoplasms/blood , Male , Retrospective Studies , Female , Middle Aged , Prognosis , Aged , Lymphocyte Count , Platelet Count , Risk Assessment/methods , Risk Factors , Biomarkers/blood , Sensitivity and Specificity , Lymphocytes
20.
PLoS One ; 19(7): e0290805, 2024.
Article in English | MEDLINE | ID: mdl-38985788

ABSTRACT

OBJECTIVE: Chronic inflammation and dyslipidemia are key risk factors for atherosclerotic cardiovascular diseases. We retrospectively explored the association between the neutrophil to lymphocyte ratio (NLR), the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C), and the neutrophil to HDL-C ratio (NHR), and the severity of coronary lesions in patients with acute coronary syndrome (ACS). METHOD: In June 2023, we selected 1210 patients who were diagnosed with ACS based on chest pain from January 2017 to December 2022. Of these, 1100 patients with abnormal coronary angiography were categorized into the experimental group, and 110 patients with normal coronary angiography were classified as the control group. We collected routine blood tests, lipid profiles, and coronary angiography results at admission (before coronary angiography). Patients were then stratified into a control group (Gensini score = 0) and an experimental group (Gensini score = 0) based on the Gensini score. The experimental group was further divided into a low score group (Gensini score < 69) and a high score group (Gensini score ≥ 69). RESULT: 1. Statistically significant differences were observed between the control and experimental groups in terms of gender, age, body mass index (BMI), hypertension, diabetes, smoking history, and counts of neutrophils (NEU), lymphocytes (LYM), monocytes (MON), eosinophils (EOS), red cell distribution width (RDW), total cholesterol (TC), HDL-C, LDL-C, NLR, LDL-C/HDL-C, and NHR (P<0.05). Furthermore, differences in BMI, hypertension, diabetes, smoking history, NEU, LYM, MON, TC, triglyceride (TG), HDL-C, LDL-C, NLR, LDL-C/HDL-C, and NHR were significant between the low and high score groups (P<0.05). 2. NEU, LYM, MON, TC, HDL-C, LDL-C, NLR, LDL-C/HDL-C, and NHR showed significant correlations with the Gensini score (r>0.2, P<0.05), with NLR and LDL-C/HDL-C showing the strongest correlations (r = 0.822, P = 0.000). 3. The Receiver Operating Characteristic (ROC) curve indicated that the combination of NLR and LDL-C/HDL-C had superior sensitivity and specificity in predicting the severity of coronary lesions, with a significant difference (P<0.05). The sensitivity was 87.1%, the specificity was 90.9%, and the cut-off point was 2.04. 4. A predictive model was developed based on the ratio of NLR and LDL-C/HDL-C to the Gensini score. The final model score was calculated as 6.803 + 7.029NLR + 13.079LDL-C/HDL-C (R2 = 0.708). CONCLUSION: Compared to NLR, LDL-C/HDL-C, and NHR, the combined NLR and LDL-C/HDL-C ratio is a more accurate marker for assessing the severity of coronary artery disease in ACS patients. Its convenience and effectiveness make it a promising tool for early assessment, timely risk stratification, and appropriate clinical intervention, ultimately improving clinical outcomes for ACS patients.


Subject(s)
Cholesterol, HDL , Cholesterol, LDL , Coronary Artery Disease , Lymphocytes , Neutrophils , Humans , Female , Male , Cholesterol, HDL/blood , Middle Aged , Coronary Artery Disease/blood , Cholesterol, LDL/blood , Aged , Retrospective Studies , Coronary Angiography , Acute Coronary Syndrome/blood , Risk Factors
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