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.
ObjectiveBased on the rat in situ perfusion system, to explore the effect of up-regulating Chemokine (C-X-C motif) receptor 4 (CXCR4) expression on bone marrow neutrophils in modulating its ECC-related rapid release. MethodsTwelve SD rats were randomly divided into fucoidan perfusion group (F, n=6) and control group (C, n=6) after in situ perfusion system establishment. Rats in F group received perfusion of fucoidan solution (total volume 6 ml, 1 h) and C group received buffer only. Femurs from two groups were dissected after one-hour perfusion and bone marrow tissues were collected. The neutrophil CXCR4 expression in two groups were compared using flowcytometry. Eighteen SD rats were randomly divided into fucoidan perfusion group (F', n=6), fucoidan and AMD-3100 perfusion group (F+AMD3100, n=6) and control group (C', n=6) after in situ perfusion system establishment. Rats received desired interventions before stimulation from ECC plasma. After that, 40-min perfusions of buffer were added and total counts of neutrophil in perfusates were compared. ResultsThe percentages of CXCR4 (+) cell and CXCR4 expression fluorescence in F group were 4.71%±0.21% and 161.3±7.8 respectively while the values were 1.11%±0.11% and 58.4±6.5 respectively in C group. Values in F group were both significantly higher than those in C group (P<0.05). The total counts of neutrophil in perfusates from F' group, F+AMD3100 and C' group were 261 393.7±12 470.6, 872 635.2±10 430.6 and 818 675.2±10 708.8, respectively. Statistically differences were observed between each other (P<0.05). ConclusionBone marrow neutrophil CXCR4 expression of SD rat could be effectively up-regulated by perfusion of fucoidan within the in situ perfusion system. ECC-plasma-stimulated bone marrow neutrophil release in rat could be inhibited by fucoidan induced up-regulation of neutrophil CXCR4 expression, and this inhibition effect could be canceled by AMD-3100 intervention.
Objective To investigate the clinical value of peripheral serum cell-free DNA/neutrophil extracellular traps (cf-DNA/NETs) level in diagnosis and severity assessment of sepsis patients. Methods Forty patients with sepsis and 40 patients with non-infectious systemic inflammatory response syndrome (nf-SIRS) were enrolled in this study. The cf-DNA/NETs level in serum of all subjects were measured. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic ability of the cf-DNA/NETs, white blood cell count (WBC), procalcitonin (PCT) and interleukin-6 (IL-6). The sepsis patients were stratified into a survival group and a death group according to the prognosis. Sequential organ failure (SOFA) score were recorded in the sepsis patients, and the correlations between SOFA and cf-DNA/NETs, PCT, WBC, IL-6 were analyzed. Results Compared with the nf-SIRS group, cf-DNA/NETs and PCT levels were significantly higher in the sepsis group (both P<0.05). WBC and IL-6 showed no significant differences between the two groups (bothP>0.05). The area under the ROC curve (AUC) of cf-DNA/NETs was 0.884 for diagnosis of sepsis, and it was higher than the AUC of PCT (0.803). The cf-DNA/NETs showed better sensitivity (81.2% and 79.2%) and specificity (81.0% and 82.4%) than PCT. cf-DNA/NETs and PCT were significantly higher in the death group than those in the survival group. Bivariate collection analysis revealed positive correlations between SOFA score and the two biomarkers of cf-DNA/NETs and PCT (r1=0.573, r2=0.518; both P<0.01). Conclusions cf-DNA/NETs and PCT have certain value in early diagnosis of sepsis, and cf-DNA/NETs shows better diagnostic value in distinguishing sepsis from nf-SIRS than PCT. cf-DNA/NETs can be used as a routine monitoring index to help assess disease severity in sepsis.
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 investigate the diagnostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) for early acute kidney injury (AKI) after tetralogy of Fallot (TOF) surgery. MethodsWe retropectively analyzed the clinical data of 113 patients underwent TOF surgery in our hospital bewteen April 2012 and April 2014. There were 67 males and 46 females at the average age of 8.28±4.75 months ranging from 5 months to 18 months. According to the different clinical manifestation of AKI, those patients were devided into a group A, group B, and group C. In the group A, there were 78 patients with 43 males and 35 females at the mean age of 8.18±3.72 months. In the group B, there were 20 patients with 12 males and 8 females at the mean age of 8.25±1.27 months. In the group C, there were 15 patients with 12 males and 3 females at the mean age of 8.09±2.92 months. We collected the blood in different time before and after the operation. At the same time, we carried on one-way analysis of variance to detect the differences among the three groups. ResultsThere was no statistical difference in the level of serum NGAL among the 3 groups before operation. Compared to pre-operation, there was no statistical difference in the level of serum NGAL among the different time of the group A (P>0.05). There was oliguria and potassium increased in the group B. After strengthening cardiac and lightening heart load, urine volume recovered. There was a transient rise in serum NGAL and the summit is 199.90±49.44 ng/ml at the 8th hour. Compared with that before operation, there was a statistical difference. After 12 hours, the serum NGAL decreased to the normal level. The serum NGAL levle of Group C had constantly increased and there was a statistical difference compared with that before the surgery. After the treatment of peritoneal dialysis, the serum NGAL returned to the normal level. The area under receiver operating characteristic (ROC) curve of serum NGAL in the group C was 0.881 (95%CI:0.73-1.00, P<0.05). ConclusionThe detection of serum NGAL level can be valuable for early diagnosis and treatment for AKI after TOF surgery.
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.
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 explore the correlation of serum neutrophil gelatinase-associated lipocalin (sNGAL) with inflammatory response in patients with community-acquired pneumonia (CAP) and assess the diagnostic value of sNGAL for severe CAP (SCAP).MethodsFrom January 2018 to June 2019, a total of 85 patients with CAP were enrolled in this study. Age, length of hospital stay, the levels of serum creatinine, blood urea nitrogen, white blood cell count,C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin, and CURB-65 score were compared between patients with SCAP (n=34) and patients without SCAP (n=51). The correlations of sNGAL with serum creatinine, blood urea nitrogen, white blood cell count, CRP, IL-6, procalcitonin, and CURB-65 score were assessed with Spearman’s correlation analysis. The area under the receiver operating characteristic (ROC) curve for sNGAL diagnosing SCAP was examined. ResultsCompared with patients without SCAP, SCAP patients demonstrated older age, longer hospital stay, higher serum CRP and IL-6 concentritions, and higher CURB-65 score (P<0.05). The Spearman’s correlation test showed that sNGAL was positively correlated with serum CRP, IL-6, PCT and CURB-65 score (rs=0.472, 0.504, 0.388, and 0.405, respectively; P<0.01). According to ROC analysis, the area under curve of sNGAL for diagnosing SCAP were 0.816, with a sensitivity of 76.56% and a specificity of 74.4% when the cut-off value was 171.0 ng/mL.ConclusionssNGAL concentration is positively correlated with the serverity of CAP. It can be regarded as a reliable indicator for diagnosis of SCAP in patients with CAP.
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.