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.
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.
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 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 early diagnostic value of urinary neutrophil gelatinase-associated lipocalin (NGAL) for acute kidney injury (AKI) after acute Stanford type A aortic dissection. Methods From January 2018 to December 2018, the clinical data of 50 patients who underwent open surgery for acute Stanford type A aortic dissection were analyzed in Nanjing First Hospital. Urine specimens were collected before and 2 hours after the aortic dissection surgery. Patients were divided into an AKI group (n=27) and a non-AKI group (n=23) according to the Kidney Disease Improving Global Outcomes criteria. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of urine NGAL. ResultsThe incidence of postoperative AKI was 54.00% (27/50). There was a statistically significant difference between the two groups in serum creatinine concentration at 2 hours after surgery and urinary NGAL concentration before the surgery (P<0.05). The area under ROC curve of preoperative urinary NGAL concentration was 0.626. When cut-off value was 43 ng/mL, the sensitivity was 40.7%, specificity was 95.7%. The area under ROC curve of urinary NGAL concentration at 2 hours after surgery was 0.655, and when the cut-off value was 46.95 ng/mL, the sensitivity was 63.0%, specificity was 78.3%. Conclusion Urine NGAL can predict postoperative AKI in patients with acute Stanford type A aortic dissection, but its value is limited.
Objective To explore the predictive value of neutrophil-to-lymphocyte ratio (NLR) in peripheral blood for postoperative complications of elective endovascular repair for abdominal aortic aneurysm (AAA). Methods From August 2016 to November 2021, the clinical data of patients with AAA who received endovascular isolation repair for the first time in the Department of Vascular Surgery of Beijing Hospital were retrospectively analyzed, including the basic information of the patients, comorbid diseases, and the largest diameter of AAA, preoperative blood labotry test, postoperative complications, long-term survival rate and other indicators. The optimal NLR in peripheral blood was determined, and the differences in postoperative complications and long-term survival rates between the high NLR group and the low NLR group were analysed. Results A total of 120 patients with AAA underwent endovascular isolation for the first time were included in this study, including 105 males and 15 females. The age ranged from 52 to 94 years, with an average of (73.3 ± 8.26) years. The largest diameter of abdominal aortic aneurysm was 35 to 100 mm, with an average of (58.5 ± 12.48) mm. The best cut-off value of NLR for predicting postoperative complications of AAA was 2.45 by using Yoden index screening. Those with NLR ≥2.45 were in the high NLR group (n=66), and those with NLR <2.45 were in the low NLR group (n=54). There was no statistically significant difference between the two groups in the incidence of overall complications and the incidence of sub-complications (P>0.05). The results of logistic regression analysis suggested that NLR was an independent risk factor for complications after endovascular repair of AAA (P<0.05). The median survival time of patients in the high NLR group and the low NLR group was 31.47 months and 35.28 months, respectively, and there was no statistically significant difference between the two groups (P>0.05). Conclusion NLR can be used as a reference predictor of complications after elective endovascular repair of AAA, but more research results are still needed to confirm.
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 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.
Glycogen storage disease type Ib (GSD Ib) is a rare disorder of glycogen metabolism, often complicated by neutropenia/neutrophil dysfunction, leading to recurrent infections and the development of inflammatory bowel disease (IBD), which severely impacts patients’ quality of life. Empagliflozin, an SGLT2 inhibitor, has demonstrated the ability to restore neutrophil counts and function, thereby improving the immunodeficiency state in GSD Ib patients. This consensus aims to provide clinical practice recommendations for the use of empagliflozin in GSD Ib based on current evidence and expert experience. The purpose of this document is to outline these key points and offer guidance for the clinical application of empagliflozin in GSD Ib.
ObjectiveTo analyze dynamic characteristics of peripheral blood cells in patients with different types of coronavirus disease 2019 (COVID-19), so as to investigate the predictive value of peripheral blood cells and their dynamic changes for clinical outcome of patients with COVID-19.MethodsForty-eight patients with COVID-19 were collected and analyzed from East Hospital of Renmin Hospital of Wuhan University from February 2 to March 15, 2020. These patients were divided into general group (group A, 17 cases), severe survival group (group B, 21 cases), and severe death group (group C, 10 cases). Blood routine examination was done and analyzed before and after admission and among the three groups. The changes of neutrophils and lymphocytes were compared. The predictive power of neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for clinical outcomes was analyzed through the receiver operating characteristic (ROC) curve.ResultsIn group B, the lymphocyte count at discharge was significantly higher than at admission (P=0.002), and the neutrophil count, NLR and PLR were significantly lower than at admission (P values were 0.012, 0.001 and 0.007, respectively). The lymphocyte counts in the A, B, and C groups were ranked from high to low upon admission, and the differences among the three groups were statistically significant (P values were 0.020, <0.001 and 0.006 for the contrasts between groups A and B, groups A and C, groups B and C, respectively), the NLR were ranked from low to high, and the differences among the three groups were statistically significant (P values were 0.001, <0.001 and 0.026 for the contrasts between groups A and B, groups A and C, groups B and C, respectively). Before discharge or death, there was no significant difference in lymphocyte counts and NLR between A and B groups (P>0.05), and there were statistically significant differences between group C and groups A and B (all P values were<0.001). The proportions of “Neutrophils Lymphocytes Convergence” in groups A and B were 64.7% and 76.2%, respectively, which were significantly higher than that in group C (10.0%). The proportions of “Neutrophils Lymphocytes Separation” in group C was 70.0%, which was significantly higher than those in groups A (0) and B (4.8%). The area under the curve of NLR predicting patients with severe disease (excluding death) was 0.843, with the sensitivity and specificity of ≥3.55 be 0.810 and 0.882; The area under the curve of lymphocyte count predicting death in severe patients was 0.845, with the sensitivity and specificity be 0.700 and 0.905, respectively.ConclusionsDynamic changes in the composition of peripheral blood cells are one of the clinical features of COVID-19, “Neutrophils Lymphocytes Convergence” and “Neutrophils Lymphocytes Separation” predict better and worse clinical outcomes, respectively. NLR and lymphocyte counts are effective indicators for predicting the severity and death of COVID-19.