The body of patient undergoing cardiopulmonary resuscitation after cardiac arrest experiences a process of ischemia, hypoxia, and reperfusion injury. This state of intense stress response is accompanied with hemodynamic instability, systemic hypoperfusion, and subsequent multiple organ dysfunction, and is life-threatening. Pulmonary vascular endothelial injury after cardiopulmonary resuscitation is a pathological manifestation of lung injury in multiple organ injury. Possible mechanisms include inflammatory response, neutrophil infiltration, microcirculatory disorder, tissue oxygen uptake and utilization disorder, etc. Neutrophils can directly damage or indirectly damage lung vascular endothelial cells through activation and migration activities. They also activate the body to produce large amounts of oxygen free radicals and release a series of damaging cytokines that further impaire the lung tissue.
Objective To study the responsiveness change of neutrophils when experiencing the second insult after the initial temperature activation in cardiopulmonary bypass (CPB) by using an in vitro model. Methods The neutrophils were isolated from blood which was drawn from each of 60 health volunteers. The samples were divided into 5 groups including normothermia, tepid temperature, moderate hypothermia, deep hypothermia, and rewarming hyperthermia by random digital table with 12 in each group according to the change of temperature during CPB. An in vitro model for studying neutrophil responsiveness was established by using a polymerase chain reaction thermocycler. Five time points were set for each group, including T0: starting CPB, T1: starting rewarming, T2: 0.5 h after rewarming, T3: 1 h after rewarming, and T4: 1.5 h after rewarming. Platelet activating factor (PAF) was added into each group at T2, T3, and T4, and then the value of membranebound elastase (MBE) activity was measured as responsiveness of neutrophils. Analysis of covariance was applied by using SPSS 13.0 for statistic analysis. If the [CM(159mm]covariance had significant difference between main effects, Bonferroni method would be applied for pairwise comparison. Results The main effect difference of neutrophil responsiveness among different groups was statistically different (F=4.372,P=0.002). MBE value had no statistical difference between the normothermia and tepid temperature groups (81.9±4.5 ng/10.6 cells vs. 76.5±3.6 ng/106 cells, P=0.134). while the MBE values in these two groups were higher than those in the other three groups (P=0.001). MBE value in the rewarming hyperthermia group was higher than that in the deep hypothermia group (61.2±2.7 ng/106 cells vs. 50.9±3.7 ng/106 cells, P=0.005). There was no statistical difference between the moderate hypothermia group (56.4±3.2 ng/106 cells) and the rewarming hyperthermia group (P=0.167), so was it between the moderate hypothermia group and the deep hypothermia group (P=0.107). The main effects of neutrophil responsiveness at different time points was statistically different (F=3.566, P=0.03) when PAF was added. MBE value at T4 was higher thanthat at T2 (70.9±2.5 ng/106 cells vs. 59.9±2.3 ng/106 cells, P=0.027). There was no statistical difference among T3 (65.5±1.8 ng/106 cells), T2 (P=0.168), and T4 (P=0.292) in MBE value. Conclusion Normothermia， tepid temperature， and rewarming hyperthermia during CPB can enhance neutrophil responsiveness and MBE release when neutrophils suffer the second insult. There is a time window for neutrophils to be easily activated during rewarming period.
ObjectiveTo explore the relevance of an increase in neutrophil count and early neurological deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke.MethodsA retrospective study was conducted on the patients who received thrombolysis treatment of alteplase within 4.5 hours after onset between January 2017 and November 2018. Based on the existence of END, the patients were divided into the END group and the non-END group. Univariate and multivariate logistic regression, and receiver operating characteristic curves were used to analyze the relevances between END and the indexes such as neutrophil count, lymphocyte count, and neutrophil to lymphocyte ratio (NLR) after thrombolysis. Paired sample t test and Wilcoxon signed-rank test were used to compare the changes of neutrophil and lymphocyte before and after thrombolysis.ResultsA total of 187 patients were included, including 48 in the END group and 139 in the non-END group. Before thrombolysis, the differences of total protein (t=2.130, P=0.035) and albumin (t=2.777, P=0.007) between the two groups were statistically significant, but the differences in other clinical indexes between the two groups were not statistically significant (P>0.05). After thrombolysis, white blood cell count, neutrophil count, NLR, fibrinase degradation product, baseline and change of National Institute of Health Stroke Scale score, proportion of cardiogenic embolism, degree of responsible vascular stenosis and anterior circulation cortical infarction site were all higher in the END group than those in the non-END group (P<0.05). The total protein, albumin, lymphocyte count and prealbumin in the END group were lower than those in the non-END group (P<0.05). Neutrophil in the END group increased significantly (Z=−2.314, P=0.021) after thrombolysis. Neutrophil count [odds ratio=1.288, 95% confidence interval (1.069, 1.552)] was one of the independent influencing factors of venous thrombolysis END, and the specificity was the highest (the sensitivity was 62.5%, and the specificity was 71.9%).ConclusionsAfter thrombolysis, elevated neutrophil count has some relevance to END. Dynamic monitoring on neutrophil count after intravenous thrombolysis treatment can predict the occurrence of END.
Objective To investigate the clinical characteristics of neutrophilic asthma ( NA) .Methods NA patients were collected from the out-patient and in-patient departments of Respiratory Diseases of Xinqiao Hospital between January 2010 and December 2010. The results of the medical records,pulmonary function tests, and induced sputum cytology were analyzed retrospectively. Results The NA patients with neutrophil percent ≥ 61% accounted for 33. 1% ( 51 /154 ) of all the asthmatics patients detected by induced sputumin the same period, and 45 cases with complete records were included. Of the 45 cases recruited, 20 cases ( 44. 4% ) were in-patients,2 cases ( 4. 4% ) were with controlled asthma, 3 cases ( 6. 7% ) were with cough variant asthma, 30 cases ( 66. 7% ) were female, 12 cases ( 26. 7% ) were atopic patients, and 27 cases ( 60% ) had acute exacerbation. The age of onset of 35 patients ( 77. 8% ) were after 12 years. FEV1% pred lt; 60% and gt; 80% was obtained in 55. 9% ( 19/34) and 14. 7% ( 5 /34) of patients respectively. The result of bronchodilator test was positive in 64% ( 16/25) of patients, and mean increase in FEV1 was 11. 7% . The percentage of neutrophil and eosinophil was ( 74. 5 ±9. 1) % and ( 2. 4 ±2. 5) % respectively in induced sputum, and 35. 6% ( 16/45) of the patients had increased eosinophil percentage ( gt;3% ) . Conclusions In our study, most of NA is severe and acute exacerbation asthma, and its clinical features are various. The mechanismand clinical significance of increased neutrophils in asthmatic patients are unclear and more studies are needed.
ObjectiveTo study the expression of lipid associated with neutrophil gelatinase associated lipocalin (NGAL) in nude mice orthotopic pancreatic cancer tissues and the relationship between the occurred and development of pancreatic cancer. MethodsThe expressions of NGAL mRNA and protein of pancreatic cancer tissues and their adjacent tissues, and normal pancreatic tissues in nude mice were detected by using RT-PCR and immunohistochemical methods. ResultsThe expressions of NGAL mRNA in pancreatic cancer tissues and adjacent tissues were significantly higher than that in normal pancreatic tissues (P < 0.05), and the expression of NGAL mRNA in pancreatic carcinoma tissues was significantly higher than that in para carcinoma tissues (P < 0.05). The strong positive expression rate of NGAL protein in pancreatic carcinoma tissues was significantly higher than thoes in para carcinoma tissues and normal pancreatic tissues (P < 0.05). ConclusionsNGAL is highly expressed in pancreatic cancer tissues, and NGAL may be an important regulatory factor in the development of pancreatic cancer.
Objective To explore the correlation and diagnostic value of neutrophil-to-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in peripheral blood of patients with exacerbation of chronic obstructive pulmonary disease (COPD). Methods One hundred patients with acute exacerbation of COPD who were hospitalized in the hospital between January 2019 and October 2020 were selected as exacerbation group, and another 100 patients with stable COPD who received treatment during the same time period were enrolled as stable group. The general data of patients were collected, and blood samples were collected to detect hemoglobin (Hb), platelet count (PLT), white blood cell count (WBC), neutrophil count, lymphocyte count and RDW, and the NLR was calculated. The correlation between the detection indicators was analyzed and receiver operating characteristic (ROC) curve was drawn to analyze the detection significance of related indicators. Results There were no statistical differences in the levels of Hb and PLT between the exacerbation group and the stable group (P>0.05). The levels of WBC, NLR, RDW and high-sensitivity C-reactive protein (hs-CRP) in the exacerbation group were significantly higher than those in the stable group (all P<0.05). NLR in the patients with acute exacerbation of COPD was positively correlated with serological indicators of WBC and hs-CRP (all P<0.05). ROC curve showed that the sensitivity and specificity of NLR in the diagnosis of acute exacerbation of COPD were 92.0% and 68.0% respectively, those of RDW were 91.0% and 58.0% respectively, those of hs-CRP were 77.0% and 71.0% respectively, and those of NLR+RDW were 90.0% and 73.0% respectively. NLR had the highest diagnostic specificity, RDW had the highest diagnostic sensitivity, and NLR+RDW had the best diagnostic efficiency. Conclusions Serological indicators of WBC, hs-CRP, NLR and RDW in patients with acute exacerbation of COPD will be abnormally increased, and NLR has a positive correlation with WBC and hs-CRP. NLR and RDW have high specificity and high sensitivity respectively in the diagnosis of patients with exacerbation of COPD, and their detection can strengthen the diagnosis and mastery of disease in patients.
The effect of neutrophil extracellular traps (NETs) on promoting intravascular microthrombi formation and exacerbating the severity of sepsis in patients has gained extensive attention. However, in sepsis, the mechanisms and key signaling molecules mediating NET formation during direct interactions of endothelial cells and neutrophils still need further explored. Herein, we utilized lipoteichoic acid (LTA), a component shared by Gram-positive bacteria, to induce NET extrusion from neutrophils firmly adhered to the glass slides coated with intercellular adhesion molecule-1(ICAM-1). We also used Sytox green to label NET-DNA and Flou-4 AM as the intracellular Ca2+ signaling indicator to observe the NET formation and fluctuation of Ca2+ signaling. Our results illustrated that LTA was able to induce NET release from neutrophils firmly attached to ICAM-1-coated glass slides, and the process was time-dependent. In addition, our study indicated that LTA-induced NET release by neutrophils stably adhered to ICAM-1 depended on Ca2+ signaling but not intracellular reactive oxygen species (ROS). This study reveals NET formation mediated by direct interactions between endothelial ICAM-1 and neutrophils under LTA stimulation and key signaling molecules involved, providing the theoretical basis for medicine development and clinical treatment for related diseases.
ObjectiveTo investigate the expression and pathological significance of neutrophil elastase (NE) and mucin 5AC (MUC5AC) in chronic obstructive pulmonary disease (COPD) rats. MethodsA total of 60 male specific pathogens free Sprague-Dawley rats were randomly divided into model group and blank group, each with 30 rats. The number of goblet cells and the positive expression of NE and MUC5AC were compared between the two groups by hematoxylin-eosin staining, alcianblue-periodic acid Schiff staining and immunohistochemical staining. ResultsNo rats died accidentally during the experiment. The number of goblet cells was 57.93±7.79 in the model group and 6.80±3.19 in the blank group, and the difference between the two groups was statistically significant (t=−44.267, P<0.05). The median (lower quartile, upper quartile) of the positive expression score of NE was 0 (0, 0) in the blank group and 2 (2, 3) in the model group, the median (lower quartile, upper quartile) of the positive expression score of MUC5AC was 0 (0, 1) in the blank group and 2 (2, 2) in the model group, and the differences between the two groups were statistically significant (P<0.05).ConclusionsThe positive expression of NE, goblet cells, MUC5AC and mucus secretion in COPD model rats increases significantly. Perhaps NE and MUC5AC can be used as target interventions to inhibit mucus hypersecretion.
Objective To observe the influence of the expression of CD18 on the neutrophile and the leukocyte adhesion to retinal vascular endothelium by hypoxia-inducible factor-1 alpha (HIF-1alpha;) in early diabetic retinopathy rats. Methods Male Sprague-Dawley rats received intraperitoneal injection of streptozotocin to induce diabetes model. 18 diabetic rats were divided into 3 groups randomly after 2 months of diabetes induction, including diabetic group (group B), HIF-1alpha; anti-sense oligonucleotides (ASODN) injection group (group C) and HIF-1alpha; sense oligonucleotides (SODN) injection group (group D), the age and weigh matched health rats were chosen as control group (group A), with 6 rats in each group. Then group A and B rats received 5% glucose solution caudalis veins injection, group C and group D rats received HIF-1alpha; ASODN and HIF-1alpha; SODN caudalis veins injection, respectively(025 mg/kg).The level of CD18 on the neutrophil isolated from the peripheral blood was measured by flow cytometry. Retinal leukostasis was quantified with acridine orange leukocyte fluorography. Results The percentage of CD18 positive neutrophil cell was（44.93plusmn;3.60）% in group B，（18.66plusmn;1.52）% in group A，（31.66plusmn;4.72）% in group C，（51.00plusmn;5.66）% in group D. Compared with each other groups，the differences are statistically significant （F=42.46, Plt;0.001）. The number of positive staining cells of retinal leukocyte was （46.16plusmn;10.68）in group A，（133.83plusmn;20.43）in group B,（99.83plusmn;9.28）in group C，（121.33plusmn;10.23） in group C. Compared group B with group C，the number of positive staining cells raised about 2.89 times；compared group B with group C and D，the differences are statistically significant （P=0.12，95% confidence interval -3.69~28.69）. Conclusions In vivo, HIF-1alpha; can decreased the expression of CD18 on neutrophils from diabetic ratsprime; peripheral blood and the collection of retinal leukostasis in the diabetic animals. HIF-1alpha; may serve as a therapeutic target for the treatment and/or prevention of early diabetic retinopathy. （Chin J Ocul Fundus Dis，2008，24：268-271）
Circadian rhythm is a physiological regulation mechanism evolved by the body to adapt to the 24-hour fluctuations in the internal and external environment. It plays an important role in many physiological and pathological processes including the immune system. Neutrophils are the most important immune cells in the human circulation, and their numbers and phenotypes also show obvious circadian fluctuations. A growing number of studies have shown that the cellular and molecular mechanisms of neutrophil circadian rhythms are disease-related. Combining the latest research on neutrophil circadian rhythm, this article briefly introduces the recruitment of neutrophils in the bone marrow, the aging of neutrophils and their infiltration into various tissues of the body, and discusses the interventions. It also discusses the therapeutic prospects based on neutrophil circadian rhythm-related mechanisms from the perspectives of intervening neutrophil aging-related chemokines and chronotherapy.