1.Increased human neutrophil lipocalin and its clinical relevance in adult-onset Still's disease.
Ji LI ; Yingni LI ; Ru LI ; Xiangbo MA ; Lianjie SHI ; Shengguang LI ; Qian GUO ; Yuan JIA ; Zhanguo LI
Chinese Medical Journal 2023;136(23):2867-2873
BACKGROUND:
Human neutrophil lipocalin (HNL) has been used extensively to differentiate acute bacterial infection from febrile diseases as a biomarker to reflect the activation of the neutrophil. The serum HNL levels in the adult-onset Still's disease (AOSD) patients with and without infection, as well as the healthy controls (HCs), were analyzed statistically in this study to evaluate the value of HNL for the diagnosis of AOSD.
METHODS:
A total of 129 AOSD patients were enrolled, from whom blood samples were drawn and the AOSD diagnosis was confirmed through the review of the medical records, where the systemic score, demographic characteristics, clinical manifestations, and laboratory parameters were also collected for the patients; in addition, a total of 40 HCs were recruited among the blood donors from the healthcare center with the relevant information collected. The HNL test was done for the blood samples with the enzyme-linked immunosorbent assay and the analyses were done for the correlations of HNL with clinical manifestations and diagnostic effectiveness.
RESULTS:
The serum HNL increased significantly in the patients with only AOSD as compared with that in the HCs (139.76 ± 8.99 ng/mL vs . 55.92 ± 6.12 ng/mL; P < 0.001). The serum HNL level was correlated with the white blood cell (WBC) count ( r = 0.335, P < 0.001), neutrophil count ( r = 0.334, P < 0.001), erythrocyte sedimentation rate ( r = 0.241, P = 0.022), C-reactive protein ( r = 0.442, P < 0.0001), and systemic score ( r = 0.343, P < 0.0001) in the AOSD patients significantly. Patients with fever, leukocytosis ≥15,000/mm 3 , and myalgia in the HNL-positive group were observed relatively more than those in the HNL-negative group ( P = 0.009, P = 0.023, and P = 0.007, respectively). HNL was a more sensitive indicator than ferritin and C-reactive protein (CRP) to differentiate the AOSD patients with bacterial infection from AOSD-only patients, and the Youden index was 0.6 for HNL and 0.29 for CRP.
CONCLUSION
Serum HNL can be used as a biomarker for the diagnosis of the AOSD, and HNL is also observed to be associated with the disease activity.
Adult
;
Humans
;
Still's Disease, Adult-Onset/diagnosis*
;
C-Reactive Protein/metabolism*
;
Neutrophils/metabolism*
;
Clinical Relevance
;
Biomarkers
;
Bacterial Infections
3.Association between increased CD177 + neutrophils and chronic activation in people living with HIV.
Lina FAN ; Yue HU ; Liying GAO ; Aiping YU ; Defa ZHANG ; Yue WU ; Fangfang YU ; Lei LI ; Bei LI ; Hongxin ZHAO ; Ping MA
Chinese Medical Journal 2023;136(24):2996-2998
4.Inertial label-free sorting and chemotaxis of polymorphonuclear neutrophil in sepsis patients based on microfluidic technology.
Chaoru GAO ; Xiao YANG ; Lijuan LIU ; Yue WANG ; Ling ZHU ; Jinhua ZHOU ; Yong LIU ; Ke YANG
Journal of Biomedical Engineering 2023;40(6):1217-1226
Reduced chemotactic migration of polymorphonuclear neutrophil (PMN) in sepsis patients leads to decreased bacterial clearance and accelerates the progression of sepsis disease. Quantification of PMN chemotaxis in sepsis patients can help characterize the immune health of sepsis patients. Microfluidic microarrays have been widely used for cell chemotaxis analysis because of the advantages of low reagent consumption, near-physiological environment, and visualization of the migration process. Currently, the study of PMN chemotaxis using microfluidic chips is mainly limited by the cumbersome cell separation operation and low throughput of microfluidic chips. In this paper, we first designed an inertial cell sorting chip to achieve label-free separation of the two major cell types by using the basic principle that leukocytes (mainly granulocytes, lymphocytes and monocytes) and erythrocytes move to different positions of the spiral microchannel when they move in the spiral microchannel under different strength of inertial force and Dean's resistance. Subsequently, in this paper, we designed a multi-channel cell migration chip and constructed a microfluidic PMN inertial label-free sorting and chemotaxis analysis platform. The inertial cell sorting chip separates leukocyte populations and then injects them into the multi-channel cell migration chip, which can complete the chemotaxis test of PMN to chemotactic peptide (fMLP) within 15 min. The remaining cells, such as monocytes with slow motility and lymphocytes that require pre-activation with proliferative culture, do not undergo significant chemotactic migration. The test results of sepsis patients ( n=6) and healthy volunteers ( n=3) recruited in this study showed that the chemotaxis index (CI) and migration velocity ( v) of PMN from sepsis patients were significantly weaker than those from healthy volunteers. In conclusion, the microfluidic PMN inertial label-free sorting and chemotaxis analysis platform constructed in this paper can be used as a new tool for cell label-free sorting and migration studies.
Humans
;
Chemotaxis
;
Neutrophils/metabolism*
;
Microfluidics
;
Cell Movement
;
Sepsis/metabolism*
5.Role of Flow Cytometry in the Diagnosis of Chronic Myeloid Leukemia.
Wei HUANG ; Rong-Rong LIU ; Yuan-Yuan WU ; Si-Si LI ; Yong-Min TANG
Journal of Experimental Hematology 2023;31(5):1327-1332
OBJECTIVE:
To analyze the immunological phenotype of chronic myeloid leukemia (CML), and explore its characteristics and significance.
METHODS:
The immunophenotypes of 40 CML children and 40 controls were analyzed by multicolor flow cytometry. CD45/SSC, as the basic gate, was used to delineate neutrophils. Then, the distribution of cluster differentiation (CD) molecules on the surface of granulocytes was analyzed in three ranges (≥1%, ≥5%, and ≥20%), and the expression rates of CD molecules (≥1% included in the statistical analysis) and the mean fluorescence intensity (MFI) were compared between the two groups.
RESULTS:
The proportion of granulocytes in the CML group was (82.1±6.4)%, which was significantly higher than (57.8±11.8)% in the control group (P <0.001). The expression rates of CD15/CD11b/CD33/CD13 in CML and control groups were high, and both distributed in the range of ≥20%. The differentiation trajectory of CD33/CD13 was normal and there were no significant differences in the expression rate and MFI between the two groups. However, both the expression rate of CD11b and CD15 MFI in the CML group were significantly lower than those in the control group (P <0.001). There were no significant differences in the expression rate and MFI of CD10 between the two groups, and the expression levels of CD10 between the two groups were consistent in different distributions. In the CML group, there was a large number of cases with abnormal high expression of CD56, 52.5% of the cases had a CD56 expression rate of ≥5%, and 42.5% had a CD56 expression rate of ≥20%, while the control group did not express CD56 (<1%). The expression distribution of CD117 was different between the two groups. In the range of expression rate ≥5%, there were 35.0% cases in the CML group, while only 2.5% in the control group. The expression rate of CD117 in the CML group was higher than that in the control group (P <0.001), though there was no significant difference in MFI.
CONCLUSION
The immunophenotyping of CML is characterized by increased proportion of mature neutrophils, decreased CD15 MFI, decreased proportion of CD11b and abnormal high expression of CD56 and CD117. Flow cytometric analysis of immunophenotype can effectively distinguish normal granulocytes from chronic granulocytes, and help in the diagnosis of CML.
Child
;
Humans
;
Flow Cytometry
;
Leukemia, Myeloid
;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics*
;
Granulocytes
;
Neutrophils
;
Immunophenotyping
6.Predictive value of PASS score combined with NLR and CRP for infected pancreatic necrosis in patients with severe acute pancreatitis.
Qianqian HE ; Mengwei CUI ; Huihui LI ; Haifeng WANG ; Jiye LI ; Yaodong SONG ; Qiaofang WANG ; Sanyang CHEN ; Changju ZHU
Chinese Critical Care Medicine 2023;35(11):1207-1211
OBJECTIVE:
To investigate the predictive value of pancreatitis activity scoring system (PASS) combined with Neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) for infected pancreatic necrosis (IPN) in patients with severe acute pancreatitis (SAP).
METHODS:
Clinical data of SAP patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected, including basic information, vital signs at admission, first laboratory indexes within 48 hours of admission. The PASS scores at admission and 24, 48 and 72 hours after admission were calculated. According to the diagnostic criteria of IPN, the patients were divided into the non-IPN group and the IPN group, and the independent risk factors of SAP complicating IPN were determined by using univariate analysis and multifactorial Logistic regression. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of NLR, CRP, and PASS score, alone and in combination for IPN in patients with SAP.
RESULTS:
A total of 149 SAP patients were enrolled, including 102 in the non-IPN group and 47 in the IPN group. The differences in PASS score at each time point, NLR, CRP, procalcitonin (PCT), blood urea nitrogen, blood chloride, and days of hospitalization between the two groups were statistically significant. Multifactorial Logistic regression analysis showed that 72 hours admission PASS score [odds ratio (OR) = 1.034, 95% confidence interval (95%CI) was 1.005-1.065, P = 0.022], NLR (OR = 1.284, 95%CI was 1.139-1.447, P = 0.000), and CRP (OR = 1.015, 95%CI was 1.006-1.023, P = 0.001) were independent risk factors for IPN in patients with SAP. ROC curve analysis showed that the area under the ROC curve (AUC) of the PASS score at 72 hours of admission, NLR, and CRP alone in predicting IPN in SAP patients were 0.828, 0.771, and 0.701, respectively. The AUC of NLR combined with CRP, PASS combined with NLR, and PASS combined with CRP were 0.818, 0.895, and 0.874, respectively. The combination of PASS score at 72 hours after admission, NLR, and CRP had a better predictive ability for IPN in patients with SAP (AUC = 0.922, 95%CI was 0.877-0.967), and the sensitivity was 72.3% when the cut-off value was 0.539.
CONCLUSIONS
The predictive value of the PASS score at 72 hours after admission, NLR and CRP in combination for IPN in SAP patients is better than that of the combination of each two and individual detection and has better test efficacy.
Humans
;
Pancreatitis, Acute Necrotizing/diagnosis*
;
C-Reactive Protein/metabolism*
;
Acute Disease
;
Neutrophils/metabolism*
;
Retrospective Studies
;
ROC Curve
;
Lymphocytes
;
Prognosis
7.Recent research on platelet-leukocyte aggregates and their role in the pathogenesis of Kawasaki disease.
Chinese Journal of Contemporary Pediatrics 2023;25(6):587-594
Activated platelets may interact with various types of leukocytes such as monocytes, neutrophils, dendritic cells, and lymphocytes, trigger intercellular signal transduction, and thus lead to thrombosis and synthesis of massive inflammatory mediators. Elevated levels of circulating platelet-leukocyte aggregates have been found in patients with thrombotic or inflammatory diseases. This article reviews the latest research on the formation, function, and detection methods of platelet-leukocyte aggregates and their role in the onset of Kawasaki disease, so as to provide new ideas for studying the pathogenesis of Kawasaki disease.
Humans
;
Mucocutaneous Lymph Node Syndrome/etiology*
;
Blood Platelets
;
Inflammation Mediators
;
Leukocytes
;
Neutrophils
8.Influence of Pre-treatment Lymphocyte/Monocyte Ratio and Neutrophil/Lymphocyte Ratio on the Prognosis of Patients with Extranodal NK/T-Cell Lymphoma.
Xiao-Yu DENG ; Ying-Yi WANG ; Qian-Qian DANG ; Tian-Song LIANG ; Ying-Juan ZHENG ; Dao-Ke YANG
Journal of Experimental Hematology 2023;31(3):707-713
OBJECTIVE:
To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL).
METHODS:
The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS.
RESULTS:
The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high β2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL.
CONCLUSION
Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.
Humans
;
Monocytes/pathology*
;
Neutrophils
;
Lymphoma, Extranodal NK-T-Cell/pathology*
;
Retrospective Studies
;
Lymphocytes
;
Prognosis
9.Predictive Value of Complete Blood Count and Inflammation Marker on Risk of Recurrence in Children with Henoch-Schönlein Purpura.
Ya-Jing JIANG ; Dan-Yang SONG ; Jin-Ling LI
Journal of Experimental Hematology 2023;31(3):837-842
OBJECTIVE:
To investigate the predictive value of complete blood count (CBC) and inflammation marker on the recurrence risk in children with Henoch-Schönlein purpura (HSP).
METHODS:
One hundred and thirty-three children with HSP admitted to Cangzhou Central Hospital from February 2017 to March 2019 were enrolled. The clinical data of the children were collected, at the time of admission CBC and C-reactive protein (CRP) were detected. After discharge, the children were followed up for 1 year, the clinical data of children with and without recurrence were compared, and multivariate logistic regression was used to analyze the risk factors affecting HSP recurrence. Receiver operating characteristic (ROC) curve should be drawn and the predictive value of CBC and CRP on HSP recurrence should be analyzed.
RESULTS:
In the follow-up of 133 children, 8 cases were lost and 39 cases recurred, with a recurrence rate of 31.20% (39/125). The age, skin rash duration, proportion of renal damage at the initial onset, percentage of neutrophils, percentage of lymphocytes, platelet count (PLT), mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), MPV/PLT ratio (MPR), and CRP level of patients with recurrence were statistically different from those without recurrence (P <0.05). Multivariate logistic regression analysis showed that long skin rash duration, renal damage at the initial onset, increased PLR, high PLT, increased MPV and elevated CRP level were independent risk factors for recurrence in children with HSP (P <0.05). The ROC curve analysis showed that the area under the curve (AUC) of the combination of the four blood and inflammation marker (PLT, MPV, PLR and CPR) in the early prediction of HSP recurrence was 0.898, which was higher than the initial renal damage (AUC=0.687) and persistent skin rash time (AUC=0.708), with a sensitivity of 84.62% and a specificity of 83.72%.
CONCLUSION
Observation of CBC and CPR can predict the risk of HSP recurrence early and guide early clinical intervention.
Humans
;
Child
;
IgA Vasculitis
;
Blood Cell Count
;
Inflammation
;
C-Reactive Protein
;
Lymphocytes
;
Neutrophils
;
Exanthema
;
Retrospective Studies
10.A YAP/TAZ-CD54 axis is required for CXCR2-CD44- tumor-specific neutrophils to suppress gastric cancer.
Pingping NIE ; Weihong ZHANG ; Yan MENG ; Moubin LIN ; Fenghua GUO ; Hui ZHANG ; Zhenzhu TONG ; Meng WANG ; Fan CHEN ; Liwei AN ; Yang TANG ; Yi HAN ; Ruixian YU ; Wenjia WANG ; Yuanzhi XU ; Linxin WEI ; Zhaocai ZHOU ; Shi JIAO
Protein & Cell 2023;14(7):513-531
As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans
;
Animals
;
Mice
;
Adaptor Proteins, Signal Transducing/metabolism*
;
Transcription Factors/metabolism*
;
Stomach Neoplasms/pathology*
;
Neutrophils/pathology*
;
Signal Transduction/genetics*
;
YAP-Signaling Proteins
;
Tumor Microenvironment
;
Hyaluronan Receptors/genetics*

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