Proportion Of Eosinophils Research Articles

Association of asthma and bronchiectasis: Mendelian randomization analyses and observational study

BackgroundPrevious studies have demonstrated that asthma is closely associated with bronchiectasis, however, the causal relationship between asthma and bronchiectasis has not been investigated in depth. Therefore, this study aims to explore the causal relationship and to identify potential factors that mediate between these two diseases.MethodAll the necessary summarized information were obtained from publicly available genome-wide association study (GWAS). Two-sample Mendelian randomization (two-sample MR) was employed to explore the causal relationship between asthma and bronchiectasis, with an additional dataset used for validation. Heterogeneity and pleiotropy analyses were utilized to verify the robustness of the results. Subsequently, mediation MR analyses were performed to identify potential mediating factors. Lastly, a retrospective observational study was conducted to validate the findings.ResultPreliminary inverse-variance weighted (IVW) results indicated there was a causal effect of asthma on bronchiectasis (odds ratio [OR] = 1.228, 95% confidence interval [CI]: 1.077–1.400, P = 0.002). Repetition validation yielded a consistent result. Mediation MR analysis demonstrated that the presence of nasal polyps (OR = 1.063, 95% CI: 1.015–1.113, mediation ratio = 30.492%, P = 0.009), acute sinusitis (OR = 1.062, 95% CI: 1.009–1.118, mediation ratio = 30.157%, P = 0.018), chronic sinusitis (OR = 1.085, 95% CI: 1.024–1.150, mediation ratio = 40.677%, P = 0.005), and peripheral eosinophil counts (OR = 1.013, 95% CI: 1.000–1.026, mediation ratio = 6.514%, P = 0.042) served as significant mediators in the occurrence and development of bronchiectasis induced by asthma. Furthermore, a retrospective observational study observed that bronchiectasis patients with asthma had a higher prevalence of sinusitis (5.043% vs 2.971%, P < 0.001), nasal polyps (0.536% vs 0.152%, P < 0.001), and rhinitis (13.197% vs 1.860%, P < 0.001). The ratio (1.950 (0.500, 5.600) vs 1.500 (0.500, 2.600), P = 0.006) and counts (0.125 (0.040, 0.363) vs 0.090 (0.030, 0.160), P < 0.001) of peripheral blood eosinophils were also elevated in bronchiectasis patients with asthma.ConclusionThe MR analysis uncovered a notable genetic association between asthma and bronchiectasis, which was partially mediated by sinusitis, nasal polyps, and eosinophils. A subsequent retrospective study provided further evidence by demonstrating that bronchiectasis patients with asthma had a higher prevalence of sinusitis, nasal polyps, an elevated proportion of eosinophils, and higher eosinophil counts.

Exogenous IL-33 promotes tumor immunity via macroscopic regulation of ILC2s.

Interleukin-33 (IL-33) is a pleiotropic molecule that plays various roles in the body. However, how exogenous IL-33 changes the tumor immune microenvironment remains unclear. Our study revealed that exogenous IL-33 exerts anti-tumor effects and effectively suppresses the progression of subcutaneous melanoma. scRNA-seq analysis revealed that exogenous IL-33 reduced neutrophils accumulation, thereby improving the inhibitory immune environment. Flow cytometry analysis revealed that exogenous IL-33 significantly increased the proportion of eosinophils and group 2 innate lymphoid cells (ILC2s). In addition, we identified genes encoding major histocompatibility complex (MHC) class II molecules in this group of ILC2s, suggesting that ILC2s may play a role in antigen presentation. In Il7rCreArg1flox/flox mice, the decrease of ILC2s led to a reduction in the proportion of eosinophils. Furthermore, we found that exogenous IL-33 effectively promoted the differentiation of ILC2s and their accumulation in tumors, thereby enhancing the anti-tumor immune response. These findings may pave the way for developing new cancer immunotherapies that use IL-33 as an activator to enhance anti-tumor immune responses.

Baseline eosinophil proportion is a useful predictor of immune-related adverse events following immune checkpoint inhibitor treatment for recurrent metastatic head and neck cancer

Background Immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs. However, predictors of irAEs remain unidentified. Objectives We evaluated the predictors of irAEs and compared the outcomes of ICIs with and without irAEs in patients with recurrent/metastatic head and neck cancers (R/M HNCs). Materials and methods We retrospectively analyzed 157 patients with R/M HNCs who were administered an anti-PD-1 antibody between September 2014 and December 2022. We examined whether various pretreatment factors were associated with irAEs. The overall survival (OS) and progression-free survival (PFS) in patients with and without irAEs were analyzed. Results Overall, 44 patients (28.0%) developed irAEs. The survival curve estimated for patients with and without irAEs showed a significant difference in PFS (p = 0.018), but not in OS (p = 0.208). Multivariate analysis revealed significant differences in relative eosinophil counts (p < 0.001), TP (p = 0.014), and NLR (p = 0.002), which may be independent predictors of irAEs. Conclusion IrAEs may be associated with higher efficacy of ICIs and longer PFS. The relative eosinophil count may be predictors of irAEs and useful in routine medical practice. Using these biomarkers to predict irAEs will help predict ICI effects and manage irAEs.

Regional differences of chronic rhinosinusitis endotypes based on tissue inflammatory and remodeling biomarkers

Objective: To analyze the characteristics of patients with chronic rhinosinusitis (CRS) in the South China region based on pathological tissue biomarkers for regional comparison. Methods: The study population consisted of CRS in-patients in the First Affiliated Hospital of Sun Yat-sen University from October 2019 to June 2022. Among all the 181 cases, 123 of them were male and 58 were female, with an average age of 40. Retrospectively collected clinical data included demographic information, preoperative symptom scores, preoperative endoscopic images, preoperative paranasal sinus computed tomography scanning images, and inflammatory serological features. In addition, 52 variables of pathological tissue biomarkers including cytokines, chemokines and remodeling factors were collected for analysis. Cluster analysis was performed on the integrated data of training set through centroid-based clustering algorithm, and the inflammatory characteristics, post-operation control status, and airway diseases comorbidity of each endotype were analyzed. R project (version 4.2.2) was used in statistical analysis. Results: Cluster analysis divided 181 patients with CRS into 4 endotypes. Cluster 1 (n=101, 55.80%) showed a locally low inflammatory status. Cluster 2 (n=23, 12.71%) showed a mixed type of inflammation with predominantly neutrophilic inflammation and tissue remodeling. Cluster 3 (n=11, 6.08%) was characterized by type Ⅱ inflammation without tissue remodeling. Cluster 4 (n=46, 25.41%) was mainly characterized by type Ⅱ inflammation with tissue remodeling, showing higher comorbidity rate of asthma and allergic rhinitis. This cluster presented more severe symptoms, significant olfactory dysfunction, extensive overall inflammation based on objective examination results, a notable increase in total eosinophil count and proportion in peripheral blood, and the highest uncontrolled rate observed one year post-surgery. In comparison to other regions, the endotype classification of CRS in Southern China was characterized by a predominant pattern of locally low inflammatory status, a moderate level of type Ⅱ inflammation with tissue remodeling, and a lesser presence of neutrophilic inflammation. Conclusion: CRS distribution in Southern China is mainly characterized by low inflammatory endotype and type Ⅱ inflammation with tissue remodeling. The latter shows more severe clinical manifestations and higher uncontrol rate after surgery.

Assessment of formed elements, vitamins B12, folic acid and iron in the blood of men with mental work

Changes in the components of the hemogram respond to the influence of living and working conditions. The goal is to assess blood parameters, vitamins B12 and B9 in men of mental work. A random sample of blood was collected from men permanently residing in Krasnoyarsk (n = 58). We assessed the degree of anthropogenic load and working conditions according to the degree of harmfulness and danger. A clinical blood test was performed, and the state of the body’s nonspecific adaptive reactions was assessed using lymphocytes. Vitamins B12, B9, and iron were determined. In terms of intellectual, emotional stress and work schedule, the work is harmful (3.3). Signs of anemia were revealed (decrease in erythrocytes in 12.1 %, hemoglobin in 10.3 %, hematocrit in 10.3 %), macrocytic (average erythrocyte volume increased in 10.3 %), hypochromic (reduced average hemoglobin concentration in erythrocyte in 22.3 %), developing due to deficiency of vitamin B12 (in 67.2 %) and B9 (in 32.8 %), iron (below the median in 51.7 %). The proportion of rod-nuclear neutrophils was reduced, the proportion of eosinophils (in 13.8 %) and monocytes (in 25.6 %) was increased, indicating sensitization, allergization, a decrease in nonspecific defense mechanisms and the presence of an inflammatory reaction in the body. The presence of stress in the body was evidenced by indicators of nonspecific adaptive reactions of the body (reactivation in 27.6 %), an increase in the proportion of monocytes in 25.6 % of those examined. It can be assumed that an environmentally unfavorable living environment and hard work in conditions of inadequate provision of the body with cyanocobalamin, folic acid and iron negatively affect the composition of the blood, which, in turn, can affect health.

Development and validation of a novel criterion of histologic healing in ulcerative colitis defined by inflammatory cell enumeration in lamina propria mucosa: A multicenter retrospective cohort in China.

Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients. We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People's Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177 + neutrophils, and CD40L + T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs . persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. We developed an ICEI for clinical diagnosis of histological healing, i.e., Y=1.701X 1 + 0.758X 2 + 1.347X 3 - 7.745 (X 1 , X 2 , and X 3 represent the proportions of CD177 + neutrophils, eosinophils, and CD40L + T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% ( P <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing ( P <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC. Chinese Clinical Trial Registry, No. ChiCTR2300077792.

Abstract 5339: Establishment of a humanized IL5/IL5RA mouse model to evaluate modulators of eosinophilic inflammation in vivo

Abstract IL-5/IL-5R signaling plays a key role in the maturation, activation, survival, and recruitment of eosinophils to sites of inflammation. Targeting this pathway is an attractive therapeutic strategy for certain inflammatory diseases, such as asthma. Here, we generated a novel humanized IL5/IL5RA model (B-hIL5/hIL5RA) to examine the utility of human IL-5/IL5R-targeting therapeutic candidates. Specifically, the entire murine Il5 coding region was replaced by the corresponding human IL5 sequence, and the human IL5RA sequence coding the extracellular domain was inserted to replace the corresponding murine sequence. Successful generation of the model was confirmed by expression of human IL-5 by ELISA and IL5RA by flow cytometry. Furthermore, the proportion of eosinophils in the blood of B-hIL5/hIL5RA mice increased after stimulation with human IL5 recombinant protein, indicating that the humanized IL5RA protein is functional. Next, the ability of the humanized mice to establish asthma-like disease was tested using ovalbumin: following a 14 day sensitization period, mice were challenged with nebulized OVA daily from day 21 until the endpoint; treatment with mepolizumab or benralizumab analog was performed. Flow cytometric analysis of the bronchioalveolar fluid indicates that treatment with mepolizumab or benralizumab analog significantly lowered the number of eosinophils when compared to the isotype control in homozygous B-hIL5/hIL5RA mice. Blood counts and quantification of lung H&amp;E sections also confirm that the treatments lowered the number of eosinophils in circulation and lung tissue, respectively. Taken together, these data indicate that B-hIL5/hIL5RA mice are a suitable preclinical model to test novel modulators of human IL-5/IL-5RA signaling. Citation Format: Suman Zhao, Shujin Zhang, Zhen Chen, Liya Yang, Mari Kuraguchi, Jiangfeng Yuan, Heiling Shen. Establishment of a humanized IL5/IL5RA mouse model to evaluate modulators of eosinophilic inflammation in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5339.

Clinicopathological Characteristics and Outcome of Cytophagic Histiocytic Panniculitis: A Single-Center, Retrospective Study.

Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis associated with systemic features characterized by the infiltration of subcutaneous adipose tissue by benign-appearing T lymphocytes and phagocytic histiocytes, mimicking hemophagocytic lymphohistiocytosis (HLH) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL). To establish the clinicopathological features and response to treatment of CHP and evaluate the prognosis of patients and guide therapy based on the current state of knowledge. Clinical, laboratory, histopathological, and outcome data of 12 patients with CHP were retrospectively collected between 2009 and 2022. All the patients presented with plaques or nodules, mostly located in the lower extremities (11/12). Fewer cases involved systemic symptoms (9/12) and laboratory abnormalities (6/12), and none were positive for serum Epstein-Barr virus (EBV)-DNA. Histopathological examination revealed mixed septal and lobular inflammatory infiltration of histiocytes and lymphocytes. Large or atypical lymphocytes were rarely present (2/12). In some patients, varying proportions of plasma cells, neutrophils, and eosinophils were observed. The extent of histocytophagy was mild (9/12), moderate (2/12), and severe (1/12). HLH was not observed in any of our cases, none of which were fatal. The uniqueness of our study lies in the presence of neutrophil-rich dermal and subcutaneous infiltrates, associated with connective tissue disorders (CTD) and streptococcal infections. Our study reveals that EBV-negative CHP tends to a better prognosis than previously research, filling the gap in the much-needed details of CHP in the Chinese population. Moreover, CHP may present as a reactive process in combined primary diseases; further studies are required to validate these findings.

Changes in peripheral blood IL-9, Th9, and BAFF levels in patients with allergic rhinitis and their clinical implications.

Allergic Rhinitis (AR), a prevalent condition in otorhinolaryngology, is mediated by Type 1 hypersensitivity through IgE, characterized by Type 2 inflammatory response and eosinophil infiltration in the nasal mucosa. Since AR disease exhibits significant heterogeneity in symptom severity, an objective assessment of AR severity may facilitate better individualized treatment. To explore the changes in peripheral blood IL-9, Th9, and BAFF levels of allergic rhinitis (AR) in patients and the clinical significance associated with it. A retrospective study selected 80 AR patients admitted from January 2022 to October 2022 as the case group, dividing them into mild and moderate-to-severe groups based on symptom scores. Concurrently, 50 patients without AR, who were treated for nasal bone fractures or underwent septoplasty, were selected as the group for comparison. Alterations in the expression levels of peripheral blood IL-9, Th9, and BAFF were analyzed and compared among the different groups. The diagnostic value of serum BAFF for the severity of AR was analyzed using the receiver operating characteristic (ROC) curve. Noticeable variations were observed in clinical variables among the three groups such as, total IgE levels, peripheral blood eosinophil count and proportion, TNSS, and VAS (P< 0.05), while no statistically significant differences were observed in other variables (P> 0.05). The comparison of IL-9, Th9, and BAFF among the three groups revealed statistically significant differences (P< 0.05). Analysis using multivariate logistic regression revealed that IL-9 (OR = 2.365), Th9 (OR = 2.186), BAFF (OR = 2.307) were influencing factors of moderate-to-severe AR (P< 0.05). The ROC curve indicated that the AUC for the diagnosis of moderate-to-severe AR by IL-9, Th9, BAFF were 0.770, 0.734, 0.761, respectively, and the combined detection AUC was 0.888, an area under the curve higher than individual testing. Changes in peripheral blood IL-9, Th9, and BAFF levels in AR patients may function as indicators to assess the level of severity in diagnostic procedures.

Bioinformatics analysis of primary biliary cholangitis key genes and molecular mechanisms

Objective: To extract the differentially expressed key genes of primary biliary cholangitis (PBC) using bioinformatics methods, so as to provide information for further study into the mechanism. Methods: The GSE119600 dataset was downloaded from the GEO database to obtain differentially expressed genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Protein-protein interaction (PPI) network reconstruction, Cytoscape software visualization, and core gene screening were performed. The area under the receiver operating characteristic curve (ROC AUC) was used to assess the diagnostic effectiveness of genes and plot the pROC software package. The x-Cell software was used to calculate the enrichment score of 34 immune cells in each sample. Finally, four key genes (PSMA4, PSMA1, PSMB1, and PSMA3) were selected. Blood samples were analyzed using the qPCR method. Results:: A total of 373 immune-related differentially expressed genes were identified. Eight genes (PSMC6, PSMB2, PSMB1, PSMA3, PSMA4, PSMA1, PSMD7, and PSMB5) were screened from the 178 nodes and 596 edges as hub genes of the PPI network, which were significantly related to amino acid metabolism, hematopoietic stem cell differentiation, cell cycle, and immune processes. PSMA4, PSMA1, PSMB1, and PSMA3 were defined as immunological biomarkers for PBC with an AUC value of the ROC curve > 0.7. Immunoinfiltrating cell analysis showed that the proportion of eosinophils was significantly higher in PBC patients compared to the control group, whereas the proportion of CD4+ memory T cells, plasma cells, Th2 cells, and cDC cells was significantly lower in PBC patients than the control group. Plasma cells were associated with all four immunological biomarkers. Seven PBC patients and seven healthy subjects were selected for peripheral blood qPCR validation, which demonstrates that PSMB1, PSMA3, PSMA1, and PSMA4 levels were significantly lower in PBC patients than healthy subjects, with a statistically significant difference. Conclusion:: Bioinformatics screened eight key genes, of which four were key immunological markers and may serve as a basis for clinical diagnosis and mechanism exploration.

Artificial intelligence-assisted prediction of olfactory disorders in patients with chronic rhinosinusitis

Objective:To analyze the influencing factors and perform the prediction of olfactory disorders in patients with chronic rhinosinusitis（CRS） based on artificial intelligence. Methods:The data of 75 patients with CRS who underwent nasal endoscopic surgery from October 2021 to February 2023 in the Department of Otorhinolaryngology Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively. There were 53 males and 22 females enrolled in the study, with a median age of 42.0 years old. The CRS intelligent microscope interpretation system was used to calculate the proportion of area glands and blood vessels occupy in the pathological sections of each patient, and the absolute value and proportion of eosinophils, lymphocytes, plasma cells and neutrophils. The patients were grouped according to the results of the Sniffin' Sticks smell test, and the clinical baseline data, differences in nasal mucosal histopathological characteristics, laboratory test indicators and sinus CT were compared between the groups. Determine the independent influencing factors of olfactory disorders and receiver operating characteristic curves（ROC） were used to evaluate the performance of the prediction model. Statistical analysis was performed using SPSS 25.0 software. Results:Among the 75 CRS patients, 25 cases（33.3%） had normal olfaction and 50 cases（66.7%） had olfactory disorders. Multivariate Logistic regression analysis showed that tissue eosinophils percentage（OR=1.032, 95%CI 1.002-1.064, P=0.036）, Questionnaire of olfactory disorders-Negative statement（QOD-NS）（OR=1.079, 95%CI 1.004-1.160, P=0.040） and Anterior olfactory cleft score（AOCS）（OR=2.672, 95%CI 1.480-4.827, P=0.001） were independent risk factors for olfactory disorders in CRS patients. Further research found that the area under the ROC curve（AUC） of the combined prediction model established by the tissue eosinophil percentage, QOD-NS and AOCS was 0.836（95%CI 0.748-0.924, P<0.001）, which is better than the above single factor prediction model in predicting olfactory disorders in CRS. Conclusion:Based on pathological artificial intelligence, tissue eosinophil percentage, QOD-NS and AOCS are independent risk factors for olfactory disorders in CRS patients, and the combination of the three factors has a good predictive effect on CRS olfactory disorders.

The Association Between Eosinophils and the Disease Process in Destructive Non-invasive Fungal Rhinosinusitis.

This study aims to investigate the significance of eosinophils in the progression and prognosis of destructive non-invasive fungal rhinosinusitis. This was a retrospective study of 126 patients who were operated on for a nasal sinus disease between 2010 and 2017; of these, 56 met the inclusion criteria. These were divided into two groups: (i) Group 1, with only the destructive non-invasive sinus polyposis type, and (ii) Group 2, with all types of nasal polyposis other than the destructive non-invasive sinus fungal polyposis type. Data including demographic data, paranasal sinuses (PNS) CT scans, pre- and post-operative eosinophils count, histopathology of polyps, and fungal cultures were collected from medical records from King Abdulaziz University Hospital, Jeddah, Saudi Arabia. A nonparametric Wilcoxon signed-rank test was used to determine a significant difference of p< 0.05. We performed multivariate analysis using repeated measure analysis of covariance (ANCOVA) and adjusted for confounders such as age, sex, pre- and post-operative IgE, fungal culture, and histopathology of the disease. Interaction between age, sex, IgE, and proportion of eosinophils was assessed at a p-value of 0.05. A significant difference was found between pre-and post-operative blood eosinophils levels in Group 1 (p= 0.01) after adjusting for confounders such as age, sex, fungal culture, pre and post IgE, and histopathology of the disease. However, no significant difference was found in Group 2 (p= 0.663) even after adjusting for age, sex, fungal culture, pre and post IgE, and histopathology of the disease. We did not find any significant interaction (P>0.05) between pre- and post-operative levels of eosinophils with age, sex, and fungal culture among Group 1 and Group 2. There is a statistically significant difference in blood eosinophils between pre- and post-operative levels in studied cases of destructive non-invasive fungal polyposis, a difference is not seen in nasal sinus polyp cases other than destructive non-invasive fungal polyposis types. High pre-operative eosinophils levels in destructive non-invasive fungal sinus polyposis types demonstrated the importance of eosinophils in the pathogenesis of this disease. The blood eosinophils can therefore be considered an important factor in the disease process and an indicator of the disease prognosis and destructive behavior.

Eosinophilic cavitary effusions in cats: 48 cases (2010-2020).

Eosinophilic effusions are commonly defined as effusions with ≥10% eosinophils. Eosinophilic cavitary effusions are infrequently observed in cats, with few case reports comprising the majority of the recent literature. The objective was to review disease associations of cats with eosinophilic cavitary effusions and to assess if a lower threshold of eosinophils (5%-9%) may warrant consideration of similar etiologies associated with effusions with ≥10% eosinophils. Cytology reports were retrospectively reviewed for all feline cavitary effusions submitted for fluid analysis from 2010 to 2020 at a veterinary teaching hospital. Cases were included if the manual leukocyte differential included ≥5% eosinophils and separated into 5%-9% and ≥10% eosinophils groups. Patient records were reviewed for associated medical conditions. A total of 669 effusions were submitted from 579 cats; 50 effusions from 48 cats had a leukocyte differential with ≥5% eosinophils. The eosinophil proportion was ≥10% in 22 cats; the most common underlying cause was neoplasia (10/22, 45%), followed by inflammatory disease (4/22, 18%), cardiac disease (3/22, 14%), suspect neoplasia (3/22, 14%), and undetermined (2/22, 9%). The underlying causes for the 26 cats with 5%-9% eosinophils were similar; neoplasia (8/26, 31%), cardiac disease (6/26, 23%), inflammatory disease (4/26, 15%), suspect neoplasia (3/26, 12%), undetermined (3/26, 12%), and idiopathic chylothorax (2/26, 8%). Cats with eosinophil proportions ≥10% in the fluid exhibited peripheral eosinophilia more frequently (35%) compared to those with 5%-9% eosinophils (5%). Consistent with the current literature, neoplasia, particularly lymphoma, remains a primary consideration for cats with eosinophilic effusions. Previously unreported associated diseases included cardiovascular and inflammatory disorders. Our findings suggest an eosinophil differential of 5%-9% is seen with similar etiologies considered for classically defined eosinophilic effusions.

Initial indicators for the prognosis of Acinetobacter Baumannii bacteremia in children

BackgroundRisk factors related to mortality due to Acinetobacter baumannii (AB) bacteremia have been unveiled previously, but early clinical manifestations of AB bacteremia based on prognosis remain uncovered.MethodsThe demographic characteristics, clinical features, antibiotic susceptibility, and outcomes of 37 hospitalized children with laboratory-confirmed AB bacteremia from Suzhou, China, were collected and analyzed retrospectively.ResultsOf the 37 children with AB bacteremia included in this study, 23 were males and 14 were females, with a median age of 4.83 (0.60 to 10.15) years. Among the children, 18 died (48.65%, 18/37) and 19 survived (51.35%, 19/37). The dead group had a significantly higher incidence of respiratory failure (p = 0.008), shock (P = 0.000), MODS (p = 0.000), neutropenia (< 1.5 × 109/L) (p = 0.000) and serious neutropenia (< 0.5 × 109/L) (p = 0.000) than those in the survival group. The death group had significantly more invasive procedures (2 or more) than that in the survival group at 2 weeks before onset (p = 0.005). The proportion of MDR-AB in the death group was significantly higher than that in the survival group (p = 0.000), while the PICS score was significantly lower in the survival group than that in the death group (p = 0.000). There was no significant difference in effective antibiotic use within 24 h between these two groups (p = 0.295). Among the 37 children with bloodstream infection of AB, 56.76% (21/37) of the underlying diseases were hematological diseases and oncology. Among them, 17 (81.00%) were died in the hospital. The proportion of white blood cells (p = 0.000), neutrophils (p = 0.042), eosinophils (p = 0.029), the ANC (p = 0.000) and lymphocyte (p = 0.000), the NLR(p = 0.011), hemoglobin (p = 0.001), platelets (p = 0.000), prealbumin (P = 0.000), LDH (p = 0.017), blood gas pH (p = 0.000), and serum potassium (p = 0.002) in the death group were significantly lower than those in the survival group. However, CRP (p = 0.000) and blood glucose(p = 0.036) were significantly higher in the death group than those in the survival group. By further multivariate analysis, CRP [OR (95% CI): 1.022(1.003, 1.041), p = 0.021] and neutropenia [OR (95% CI): 21.634 (2.05, 228.313, p = 0.011] within 24 h of infection were independent risk factors for death in children with AB bacteremia. When CRP was higher than 59.02 mg/L, the sensitivity of predicting mortality was 88.9%, and the specificity was 78.9%. And the sensitivity and specificity of neutropenia for predicting mortality were 83.3% and 84.2%.ConclusionsAB bacteremia has a high mortality in children, especially in patients with hematological diseases and oncology. Many early indicators were associated with poor prognosis, while elevated CRP and neutropenia were the independent predictors for the 30-day mortality of children with laboratory-confirmed AB bacteremia.

Female-specific enhancement of eosinophil recruitment and activation in a type 2 innate inflammation model in the lung.

A sex disparity in asthma prevalence and severity exists in humans. Multiple studies have highlighted the role of innate cells in shaping the adaptive immune system in chronic asthma. To explore the sex bias in the eosinophilic response, we delivered IL-33 to the lungs of mice and delineated the kinetics by which the inflammatory response was induced. Our data demonstrate that females recruited more eosinophils capable of responding to IL-33. Eosinophil activation occurred selectively in the lung tissue and was enhanced in females at all time points. This increase was associated with increased ex vivo type 2 cytokine and chemokine production and female-specific expansion of group 2 innate lymphoid cells lacking expression of the killer-cell lectin-like receptor G1. Our findings suggest that the enhanced eosinophilic response in females is due, firstly, to a greater proportion of eosinophils recruited to the lungs in females that can respond to IL-33; and secondly, to an enhanced production of type 2 cytokines in females. Our data provide insight into the mechanisms that guide the female-specific enhancement of eosinophil activation in the mouse and form the basis to characterize these responses in human asthmatics.

Morphological Features and Morphometric Parameters of Peripheral Blood Eosinophiles in Raccoon Dogs &lt;i&gt;Nyctereutes procyonoides&lt;/i&gt; (Grey, 1834)

The aim of this work was to analyze the morphology and morphometric parameters of peripheral blood eosinophils and eosinophilic granules in raccoon dogs Nyctereutes procyonoides (Grey, 1834). On blood smears stained by Pappenheim, the composition of the leukocyte formula was determined, the morphological features and morphometric parameters of eosinophils and their granules were evaluated. Cytochemical methods revealed the localization of peroxidase and cationic proteins in eosinophils. ANOVA was used to assess the effect of sex. As a result of the study, it was found that raccoon dogs are characterized by a high relative content of eosinophils (7–10%), as well as the presence of large secretory granules in them. Along with the common eosinophils, there were cells with abnormal granularity (low number of secretory granules, the presence of vacuole-like granules that did not stain with the dyes used). The influence of sex was expressed in a higher proportion of eosinophils with abnormal granularity in males compared to females, while the latter had higher morphometric parameters (the number and average area of granules in one cell, the ratio of the area occupied by granules to the area of the cell). Since the causes of abnormally granular eosinophils in raccoon dogs are not completely clear, there is a need for further research into this issue.

Protective effects and mechanisms of N-acetylcysteine on indomethacin-induced intestinal injury in a porcine model

This study aimed to investigate the effect of N-acetylcysteine (NAC) on indomethacin (IDMT)-induced intestinal injury in a piglet model and explore the underlying molecular mechanisms. Piglets were randomly divided into 3 treatment groups: (1) control group; (2) IDMT group; (3) NAC+IDMT group. The results showed that NAC administration significantly increased the average daily gain of piglets, attenuated the intestine hyperemia, and restored normal jejunal morphology. Further studies indicated that NAC administration significantly increased plasma citrulline concentration and jejunal villin expression, but decreased the content of proinflammatory cytokines in plasma and jejunum of IDMT-stimulated piglets. NAC administration selectively decreased the proportion of eosinophils but not neutrophils in plasma. Furthermore, NAC administration significantly increased the activities of superoxide dismutase and catalase in plasma but decreased the concentrations of hydrogen peroxide (plasma) and malondialdehyde (plasma and jejunum), as well as the activity of myeloperoxidase (jejunum) when comparing NAC+IDMT group with IDMT group. Gene Ontology analysis showed that the significantly enriched molecular function term was “ubiquitin-like protein ligase binding” for NAC+IDMT versus IDMT differentially regulated genes. In the biological process category, differentially regulated genes of NAC+IDMT versus IDMT were mainly enriched in immune-related terms. The major enrichments for differentially regulated proteins (DRPs) of NAC+IDMT versus IDMT were terms involved in lipid metabolism and immune response. KEGG pathway enrichment analysis showed that “arginine biosynthesis” was a significant enrichment term for the DRPs of NAC+IDMT versus IDMT. Further studies demonstrated that NAC administration up-regulated argininosuccinate synthase 1 mRNA expression and down-regulated arginase mRNA expression in the jejunum of IDMT-stimulated piglets. Moreover, the content of nitric oxide was restored to a normal level with the reduction of nitric oxide synthase activity. NAC administration ameliorated intestinal injury in IDMT-challenged piglets by enhancing antioxidant and anti-inflammatory functions and modulating arginine metabolism in the small intestine.

Exploring the potential targets of Biling Weitong Granules on visceral hypersensitivity through integration of network pharmacology and in vivo analysis

Ethnopharmacological relevanceBiling Weitong Granules (BLWTG) are a newly developed traditional Chinese medicine prescription based on the ancient prescription Jinlingzi San and Zuojin Wan. It is used for the treatment of functional gastrointestinal disorders (FGIDs) featured as visceral hypersensitivity (VH). However, its active ingredients and protein targets involved still remain unknown. Aim of the studyTo explore the potential targets of BLWTG for the treatment of visceral hypersensitivity. Materials and methodsActive components and their protein targets of BLWTG were screened from TCMSP database and the component-target network were constructed with Cytoscape software. Irritable bowel syndrome (IBS) was the representative disease in this study and information on its linked pathways was obtained from NCBI, Drugbank and Genecard. Target pathways of BLWTG were analyzed through KEGG to verify the correlation with IBS related pathways.Then, the VH mouse models was induced by maternal separation (MS), randomly divided into normal saline (NS),BLWTG1 (low-dosage) and BLWTG2 (high-dosage) group. After intervention, threshold intensity of colorectal distension (CRD) and body weight were measured to evaluate relief of IBS symptoms. Elisa was performed to evaluate 5-HT concentration changes of colon tissues. Flow cytometry was performed to assess changes of colon eosinophils and mast cells proportion. Transcriptome sequencing was employed to analyze changes of pathways and differential genes. Results199 protein targets and 132 active components of BLWTG were identified. KEGG analysis revealed the overlap between BLWTG target pathways and IBS related pathways such as neuroactive ligand-receptor interaction, tryptophan metabolism and inflammatory reaction. 34 genes were not only BLWTG target proteins but also recognized targets for treating IBS.After maternal separation (MS), the mice showed a significant decrease in threshold intensity of CRD, a progressive decrease in body weight and an increase of 5-HT concentration of colon tissue. The proportion of mast cells and eosinophils in the colon increased. Differential genes including Hp,Ido1 and Aqp7 were significantly increased in MS mice group and IBS-related pathways were upregulated. After treatment of BLWTG, threshold intensity of CRD and body weight were significantly improved and IBS related pathways were downregulated. In addition, among BLWTG protein targets, Il1b,Tnf,Adrb1 and Nos2 were found upregulated in MS+NS mice and downregulated after BLWTG intervention through combination of transcriptome sequencing. ConclusionsIn maternal separation-induced mouse models, BLWTG could alleviate visceral hypersensitivity, possibly through downregulation of 5-HT concentration and eosinophils and mast cells proportion in colon and critical pathways such as neuroactive ligand-receptor pathway. Potential targets of BLWTG including Il1b,Tnf,Adrb1 and Nos2 were found through integration of network pharmacology database and transcriptome sequencing, providing evidence for further study on mechanisms underlying visceral hypersensitivity.

Cerebral sparganosis in a child with corpus callosum invasion: a case report

BackgroundInvasion of the corpus callosum by sparganosis is rare in children. After invading the corpus callosum, sparganosis has various migration modes, which can break through the ependyma and enter the ventricles, thus causing secondary migratory brain injury.Case presentationA girl aged 4 years and 7 months presented with left lower limb paralysis for more than 50 days. Blood examination showed that the proportion and absolute number of eosinophils in the peripheral blood were increased. Furthermore, enzyme-linked immunosorbent assay of serum and cerebrospinal fluid samples revealed positivity for IgG and IgM antibodies for sparganosis. Initial magnetic resonance imaging (MRI) revealed ring-like enhancements in the right frontoparietal cortex, subcortical white matter, and splenium of the corpus callosum. Within 2 months, a fourth follow-up MRI showed that the lesion had spread to the left parietal cortex, subcortical white matter, and deep white matter in the right occipital lobe and right ventricular choroid plexus, with left parietal leptomeningeal enhancement.ConclusionMigratory movement is one of the characteristics of cerebral sparganosis. When sparganosis invades the corpus callosum, clinicians should be aware that it may then break through the ependyma and enter the lateral ventricles, leading to secondary migratory brain injury. Short-term follow-up MRI is necessary to evaluate the migration mode of sparganosis and dynamically guide treatment strategies.

Bioinformatics analysis reveals the landscape of immune cell infiltration and novel immune-related biomarkers in moyamoya disease.

Objective: This study aimed to identify immune infiltration characteristics and new immunological diagnostic biomarkers in the cerebrovascular tissue of moyamoya disease (MMD) using bioinformatics analysis. Methods: GSE189993 and GSE141022 were downloaded from the GEO database. Differentially expressed gene and PPI analysis were performed. After performing WGCNA, the most significant module associated with MMD was obtained. Next, functional pathways according to GSEA, GO, and KEGG were enriched for the aforementioned core genes obtained from PPI and WGCNA. Additionally, immune infiltration, using the CIBERSORT deconvolution algorithm, immune-related biomarkers, and the relationship between these genes, was further explored. Finally, diagnostic accuracy was verified with ROC curves in the validation dataset GSE157628. Results: A total of 348 DEGs were screened, including 89 downregulated and 259 upregulated genes. The thistlel module was detected as the most significant module associated with MMD. Functional analysis of the core genes was chiefly involved in the immune response, immune system process, protein tyrosine kinase activity, secretory granule, and so on. Among 13 immune-related overlapping genes, 4 genes (BTK, FGR, PTPN11, and SYK) were identified as potential diagnostic biomarkers, where PTPN11 showed the highest specificity and sensitivity. Meanwhile, a higher proportion of eosinophils, not T cells or B cells, was demonstrated in the specific immune infiltration landscape of MMD. Conclusion: Immune activities and immune cells were actively involved in the progression of MMD. BTK, FGR, PTPN11, and SYK were identified as potential immune diagnostic biomarkers. These immune-related genes and cells may provide novel insights for immunotherapy in the future.