Objective
To explore the effect of leukotriene receptor antagonist montelukast on physicochemical property of sputum and airway mucus hypersecretion in patients with acute exacerbation of bronchiectasis.
Methods
Eighty-four inpatients with acute exacerbation of bronchiectasis were randomly divided into a control group and an experiment group, with 42 cases in each group. The control group received conventional therapy and the experiment group took orally montelukast 10 mg before sleep every day based on conventional therapy for two weeks. At admission and 15 days after admission, the amount in 24 hours, dry/wet weight ratio and viscosity of sputum were observed while the levels of neutrophil elastase (NE) and mucin MUC5ac in sputum were determined by ELISA. The pulmonary ventilation function, airway resistance and blood gas analysis were also measured.
Results
The sputum amount in 24 hours, dry/wet weight ratio and viscosity of sputum, NE and MUC5ac of sputum, pulmonary ventilation function, blood gas analysis and airway resistance were declined or improved remarkably after treatment compared with before treatment in two groups (P<0.05). Meanwhile, the sputum amount in 24 hours [(5.62±1.83) g vs. (7.53±2.32) g], NE [(3.85±0.97) μg/ml vs. (4.54±1.03) μg/ml], MUC5ac [(0.65±0.21) μg/ml vs. (0.82± 0.29) μg/ml] and the airway resistance [(119.16±11.76)% vs. (128.37±12.08)%] were declined remarkably in the experiment group compare with the control group after treatment (all P<0.05). The viscosity of sputum between the two groups after treatment showed no significant difference.
Conclusion
In patients with acute exacerbation of bronchiectasis, montelukast can reduce amount of sputum and airway resistance, reduce expression of mucin MUC5ac through down-regulation of NE, thus inhibit airway mucus hypersecretion.
ObjectiveTo determine whether there is an imbalance of KLF2/RelA in peripheral blood neutrophils in patients with bronchial asthma, and explore the relationship between KLF2/RelA imbalance and neutrophil apoptosis.MethodsFrom April 2011 to April 2012, a total of 39 patients with acute attack of asthma in Hunan People's Hospital and Third People's Hospital of Changsha were enrolled, with 13 cases in mild asthma group, 17 cases in moderate asthma group, and 9 cases in severe asthma group. Fifteen healthy subjects were recruited as control group. Peripheral blood were collected from all subjects followed by separation of neutrophils. The apoptosis of neutrophils were measured by flow cytometry. The expression of KLF2 and RelA were detected by Western blot. The relationship between the ratio of KLF2/RelA and neutrophil apoptosis rate was analyzed by Pearson correlation test.ResultsNeutrophil apoptosis rates in the mild, moderate and severe asthma groups [(4.45±0.76)%, (2.10±0.25)%, (1.81±0.67)%, repectively] were lower than that in the healthy control group [(5.36±0.57)%, all P<0.01]. The apoptosis rates of neutrophils in the moderate and severe asthma groups were lower than that in the mild asthma group (bothP<0.01), but there was no significant difference between the moderate asthma group and the severe asthma group (P>0.05). The ratios of neutrophil KLF2/RelA in the mild, moderate and severe asthma groups were lower than that in the normal control group (0.667±0.351, 0.384±0.203, 0.536±0.293vs. 4.038±2.011, all P<0.01). There was no significant difference between the groups of mild, moderate and severe asthma (P>0.05). The neutrophil apoptosis rate was positively correlated with the percentage of neutrophil KLF2/RelA (r=0.592 0, P<0.000 1).ConclusionThere is an imbalance of KLF2/RelA in peripheral blood neutrophils in patients with bronchial asthma, and the imbalance of KLF2/RelA may be the mechanism of apoptosis of peripheral blood neutrophils.
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.
Neutrophil extracellular traps (NETs), composed of deoxyribonucleic acid (DNA), histones, and granule enzymes, exhibit a “double-edged sword” effect in retinal neovascularization (RNV) diseases. The formation of NETs involves classical lytic and non-lytic pathways, as well as peptidylarginine deiminase 4 (PAD4)-dependent and reactive oxygen species-dependent molecular mechanisms. Across different types of RNV, the roles of NETs vary markedly. In diabetic retinopathy, NETs accelerate disease progression by amplifying inflammatory responses, disrupting the blood-retinal barrier, and increasing vascular permeability. During specific stages of retinopathy of prematurity, NETs participate in the clearance of senescent vessels and promote beneficial vascular remodeling. In retinal vein occlusion, their pro-coagulant and pro-inflammatory properties may exacerbate thrombosis and ischemia. The functions of NETs are dynamically regulated by disease stage, microenvironmental factors, and interactions with immune cells. Therefore, therapeutic strategies aimed at clearing NETs (e.g., deoxyribonuclease I) or inhibiting NET formation (e.g., PAD4 inhibitors) may serve as complementary approaches to current anti-vascular endothelial growth factor therapies, although further studies are needed to elucidate optimal intervention timing, safety, and combination treatment strategies for clinical translation.
ObjectivesTo assess the predictive value of neutrophils-to-lymphocytes ratio (NLR) in the diagnosis of children complicated appendicitis.MethodsThe clinical data of patients with acute appendicitis treated in Department of Pediatric Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University from January 2014 to June 2017 were analyzed retrospectively. Based on the pathology results, patients were divided into two groups: simple appendicitis and complicated appendicitis. The differences of age, gender, disease time, fever, highest temperature, emesis, right lower abdominal pain, blood indicators, and ultrasound results between the two groups were analyzed. Useful parameters to aid in the diagnosis of children complicated appendicitis were screened through single-factor and multiple-factor analysis. The predictive value of the parameters was evaluated by ROC analysis, sensitivity and specificity.ResultsA total of 235 patients was evaluated and divided into simple appendicitis group (179 patients) and complicated appendicitis group (56 patients). Logistic regression analysis revealed that NLR was the independent risk factor for diagnosis of children complicated appendicitis. When NLR>11.74, the Youden index for predictive complicated appendicitis was the biggest, reaching 0.325, and the sensitivity and specificity were 47.8% and 84.7%, respectively (OR=3.121, 95%CI 2.036 to 4.783).ConclusionsThe preoperative NLR is a certain indicator for predicting children complicated appendicitis, and can be used as reference to whether or not receive an operation.
ObjectiveTo evaluate the efficacy and reversible effect of anti-VCAM-1 ultrasound-targeted microbubbles on extracorporeal circulation (ECC) related bone marrow neutrophil releasing.
MethodsThirty-six male SD rats were randomly divided into 6 groups with 6 rats in each group, including an antibody group (group A), antibody with ultrasound group (group AU), targeted microbubble group (group T), targeted microbubble rupture group (group TU), post-ECC plasma simulation group (group MC) and control group (group C) after in situ perfusion model establishment. Rats in group C received buffer perfusion for 4 cycles, and rats in other groups received perfusion for 5 cycles. After buffer perfusion for the first cycle, post-ECC plasma was infused to each group from the second cycle to the fifth cycle in group MC, A, AU, T and TU. Rats in group A and AU received injection with anti-VCAM-1 antibodies, while rats in group T and TU were given anti-VCAM-1 targeted microbubbles after the second perfusion cycle. Same ultrasound radiation was given to group AU and TU in the third perfusion cycle. Neutrophil counts from perfusate were compared among the 6 groups.
ResultsUnder simulated inflammatory condition after ECC, compared with group MC, significant reduction of neutrophil count released from bone marrow was found in group A and T, especially in group T (P < 0.05). After ultrasonic radiation, neutrophil mobilization recovered in group TU and its neutrophil count was significantly higher than that of group T (P < 0.05). There was no significant difference in neutrophil count between group A and AU in each perfusion cycle (P > 0.05).
ConclusionsAnti-VCAM-1 targeted microbubbles can block the binding of VCAM-1 and its ligand, and form a barrier on the surface of bone marrow sinusoids endothelium to inhibit neutrophils migrating and releasing. The binding of VCAM-1 and its ligand on microbubbles is separated by cavitation of disrupting microbubbles with ultrasound, and neutrophils recover the ability to cross the sinusoidal endothelium of bone marrow in inflammatory conditions to achieve the controllability of neutrophil releasing.
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.
ObjectiveTo evaluate the value of serum procalcitonin (PCT) level after conventional intravenous antibiotic treatment to predict the risk of re-exacerbation, and vertify the feasiblity of an additional course of oral antibiotics after discharge to reduce the risk of re-exacerbation.
MethodsThe patients who hospitalized in West China Hospital from October 2012 to October 2013 because of infectious acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were recruited. The concentrations of PCT and C-reactive protein (CRP), the number of white blood cell (WBC) and neutrophil percentage at the end of intravenous antibiotic therapy were recorded. The information about additional course of antibiotics was collected according to the medical instruction and visit. The subjects were followed up for 1 year.The time to the first re-exacerbation and frequencies of exacerbations were recorded. The Cox regression model was used to estimate the hazard rations (HR).
ResultsOne hundred and thirty-eight eligible patients were included totally. The HRs in PCT≥0.11μg/L and neutrophil percentage≥70% were 1.462 (P=0.035) and 1.673 (P=0.005) respectively, suggesting higher risk of re-exacerbation. There was no relationship of CRP (P=0.330) or WBC (P=0.432) with the risk of re-exacerbation. Generally an additional course of antibiotics had no effects on re-exacerbation (P=0.231) but this therapy could reduce the risk of re-exacerbation in high PCT level group (HR=2.29, P=0.004).
ConclusionsSerum PCT concentrations and neutrophil percentage after conventional intravenous antibiotic treatment can predict the risk of re-exacerbations in the future. An additional course of antibiotics in the patients with high PCT level can reduce the risk of re-exacerbation.
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.
Cell migration is defined as the directional movement of cells toward a specific chemical concentration gradient, which plays a crucial role in embryo development, wound healing and tumor metastasis. However, current research methods showed low flux and are only suitable for single-factor assessment, and it was difficult to comprehensively consider the effects of other parameters such as different concentration gradients on cell migration behavior. In this paper, a four-channel microfluidic chip was designed. Its characteristics were as follows: it relied on laminar flow and diffusion mechanisms to establish and maintain a concentration gradient; it was suitable for observation of cell migration in different concentration gradient environment under a single microscope field; four cell isolation zones (20 μm width) were integrated into the microfluidic device to calibrate the initial cell position, which ensured the accuracy of the experimental results. In particular, we used COMSOL Multiphysics software to simulate the structure of the chip, which demonstrated the necessity of designing S-shaped microchannel and horizontal pressure balance channel to maintain concentration gradient. Finally, neutrophils were incubated with advanced glycation end products (AGEs, 0, 0.2, 0.5, 1.0 μmol·L?1), which were closely related to diabetes mellitus and its complications. The migration behavior of incubated neutrophils was studied in the 100 nmol·L?1 of chemokine (N-formylmethionyl-leucyl-phenyl-alanine) concentration gradient. The results prove the reliability and practicability of the microfluidic chip.
