Basophils Research Articles

Establishment and verification of reference intervals for blood cell analysis in extremely high altitude.

This study aimed to establish the reference intervals for complete blood count (CBC) in healthy adults at very high altitudes. This study recruited 4,863 healthy adults (3,598 males and 1,265 females) who received routine health check-ups at Ali District People's Hospital from January 2019 to December 2021 through the LIS system. CBC was detected by the XT-4000i automatic cell analyzer and statistically analyzed by SPSS 23.0 software (between-groups comparison, diagnostic concordance comparison). In addition, 20 health check samples were collected in 2022 to validate the established reference intervals. The CBC count showed a non-normal distribution in each item separately. The white blood cell (WBC), neutrophil (NEUT), lymphocyte (LYMPH), monocyte (MONO), eosinophil (EO), basophil (BASO), red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean hemoglobin content (MCH), and mean erythrocyte hemoglobin concentration (MCHC) levels of healthy adults were significantly different from the national clinical reference range (p < 0.05). There were significant differences between males and females in RBC, HGB, and HCT levels (p < 0.05). The new reference intervals were less consistent with the expert consensus CBC reference intervals (p < 0.05). Compared with the other reference intervals, the diagnostic value of the reference screening interval established was significantly higher in this study (p < 0.05). The reference range established is verified by 20 independent samples from 2022, and the results are acceptable. This study preliminarily established reference intervals for complete blood counts of healthy adults at high altitudes in the Ali region of Tibet to provide a reference point for understanding routine blood markers in permanent residents of high-altitude environments and illustrate the need for regular establishment of laboratory reference intervals on a regular basis.

Do Not Forget the Granulocytic Compartment's Role in T cell-Mediated Antitumor Immunity.

Antitumor immune responses are predominantly mediated by CD8+ cytotoxic T cells (CTLs). But immune-modulatory factors in the tumor microenvironment determine the effectiveness of these responses. In this issue, Wei and colleagues report a new role for CTL-derived IL3 in stimulating basophilic granulocytes to produce IL4, which, in turn, activates, reprograms, and stabilizes CTLs. These findings stress the importance of the crosstalk between the innate and adaptive immune systems to elicit efficient antitumor immunity. See related article by Wei et al., p. 822 (3).

The predictive value of hematological inflammatory markers for severe oral mucositis in patients with nasopharyngeal carcinoma during intensity-modulated radiation therapy: A retrospective cohort study

BackgroundThis study aims to investigate the predictive value of the circulating blood cell count, including neutro-philto-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), and thesystemic inflammation index (SII) for the development of severe oral mucositis (SOM) induced by radiation in patients undergoing radiotherapy for nasopharyngeal carcinoma (NPC). MethodsIn this retrospective study, 142 NPC patients were screened, and based on mucositis toxicity grade, they were categorized into two groups: SOM and nonSOM. Peripheral blood cell counts were conducted prior to Intensity-Modulated Radiation Therapy (IMRT). Associations between blood cell count, NLR, PLR, SII, and SOM occurrence were examined. ResultsRevealed elevated NLR and SII levels, along with reduced lymphocyte (LYM), eosinophil (EOS), and basophil (BAS) in patients with SOM. LYM, EOS, BAS, NLR, and SII were effective predictors of the severity of radiation-induced oral mucositis (RIOM) in NPC patients. ConclusionsThe occurrence of SOM was strongly linked to the hematological status at the start of Radiation Therapy (RT). Integrating BAS count and NLR into comprehensive risk prediction models could prove valuable for predicting SOM in NPC patients.

Short-term exposure to air pollution on peripheral white blood cells and inflammation biomarkers: a cross-sectional study on rural residents

Effects of short-term exposure to ambient air pollution on systemic immunological and inflammatory biomarkers in rural population have not been adequately characterized. From May to July 2021, 5816 participants in rural villages of northern Henan Province, China, participated in this cross-sectional study. Blood biomarkers of systemic inflammation were determined including peripheral white blood cells (WBC), eosinophils (EOS), basophils (BAS), monocytes (MON), lymphocytes (LYM), neutrophils (NEU), neutrophil-lymphocyte ratio (NLR), and serum high-sensitivity C-reactive protein (hs-CRP). The concentrations of ambient fine particulate matter (PM2.5), PM10, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were assessed up to 7 days prior to the blood draw. A generalized linear model was used to analyze the associations between air pollution exposure and the above-mentioned blood biomarkers. Significantly positive associations were revealed between PM2.5, CO and WBC; CO, O3 and LYM; PM2.5, PM10, SO2, CO and NEU; PM2.5, PM10, SO2, CO and NLR; PM2.5, PM10, SO2, NO2, CO, O3 and hs-CRP. Meanwhile, negative associations were found between SO2 and WBC; PM2.5, PM10, NO2, CO, or O3 and EOS; PM2.5, SO2, or CO and BAS; SO2, NO2 or O3 and MON; PM2.5, PM10, SO2, or NO2 and LYM. Moreover, men, individuals with normal body mass index (BMI), current smokers, and those older than 60 years were found vulnerable to air pollution effects. Taken together, short-term exposure to air pollution was associated with systemic inflammatory responses, providing insight into the potential mechanisms for air pollution-induced detrimental systemic effects in rural residents.

Certain immune parameters may have a significant impact on suicidal behaviour - a naturalistic study among psychiatric in-patients

IntroductionSeveral research already proved the role of certain immunological factors (neutrophil-lymphocyte (NLR), monocyte-lymphocyte (MLR) and platelet-lymphocyte (PLR) ratio, and C-reactive protein (CRP)) in the background of suicidal behaviour.ObjectivesThe aim of this research was to study the association between routinely measurable low-grade inflammation parameters and suicidal behaviour among patients in the acute psychiatric care setting.MethodsThe study population included psychiatric in-patients (N=100) consecutively treated with depressive disorders and/or suicidal behaviour in a University Clinic between December 1, 2020 and December 31, 2021. Three different patient-groups were generated based on their suicidal behaviour: suicide attempters (N=55) including recent attempters(N=36) and past attempters (N=19) and non-suicidal patients (N=45), who never had a suicide attempt. Basic socio-demographic data, the severity of depression and immunological parameters (white blood cell count: lymphocytes, monocytes, neutrophil, eosinophil, basophil granulocytes; thrombocytes; C-reactive protein) were recorded.Descriptive analyses and multivariate regression model were performed with RStudio version 4.2.3.ResultsCRP was significantly higher (2.00 vs. 1.00; p=0.007) in suicidal patients (N=55), however other immunological parameters did not differ significantly between the suicidal and the non-suicidal groups (NLR: 2.02 vs. 2.19; MLR: 0.22 vs. 0.11; PLR: 118 vs. 130). NLR and MLR showed significantly higher values (NLR: 2.83 vs. 1.93, p=0.021; MLR: 0.28 vs. 0.11, p=0.01) for those who currently attempted suicide (N=36) compared to the patients with no or past suicide attempt (N=64). In the regression analysis, the NLR and MLR showed significantly higher values in current suicide attempters even when gender, age, suicidal risk and severity of depression were included in the model. However, no significant differences were found when comparing current and past suicide attempters with the non-suicidal patients.ConclusionsDespite the small number of cases in the samples, our results confirmed the association of certain immunological parameters (NLR, MLR) and acute suicidal behaviour. This relationship was found to be independent of depression and its severity. Our data suggest that, unlike the NLR and MLR parameters, the higher CRP value may not be related to acute suicide attempt, but rather to suicidal vulnerability, as a trait-marker. Markers of chronic systemic inflammation may help in the prediction of suicidal behaviour and in the development of new therapeutic options, however, further prospective studies are needed to identify the specific role of immunological factors in suicidal behaviour more precisely.Disclosure of InterestNone Declared

Predicting acute myocardial infarction from haematological markers utilizing machine learning and explainable artificial intelligence

Myocardial infarction (MI) is the leading cause of human death globally. It occurs when a blockage in an artery prevents blood and oxygen from reaching the heart muscle, causing tissues in the heart muscle to die. This leads to a necessity to develop a method to diagnose MI’s early, preventing further complications such as irregular heart rhythm, heart failure or even cardiac arrest. This research aims to develop a more accurate machine learning (ML) model to help predict acute myocardial infarction (AMI) with a greater degree of accuracy without invasive procedures using additional explainable artificial intelligence (XAI) techniques which will help medical practitioners to better diagnose AMI more precisely. According to the results, the random forest classifier model gave the highest accuracy of 86%. XAI techniques were used to visualize the data and results, and determined white blood cell (WBC) count to be the most crucial feature in classification, followed by neutrophil (NEU) count, neutrophil-lymphocyte (NEU/LY) ratio, platelet width of distribution (PDW) values and basophil (BA) counts. The developed model can help medical practitioners make a more accurate early diagnosis of AMI using readily available hematological parameters, enabling practitioners to provide superior care to a diverse range of individuals.

Study on the correlation between controlling nutritional status score and clinical biochemical indicators in patients with colorectal cancer

PurposeThe controlling nutritional status (CONUT) score is an important tool for predicting the prognosis of colorectal cancer (CRC); however, its effectiveness is relatively insufficient. This study aimed to screen for more effective clinical indicators as supplements to the CONUT scoring system and improve the predictive value of CRC prognosis. Patients and methodsBetween 2014 and 2020, the clinical information of all CRC patients in our unit was retrospectively collected, and the CONUT scores were calculated based on the levels of serum albumin (ALB), lymphocytes (LC), and total cholesterol. The included patients were divided into the following three groups: normal nutrition (0–1), mild malnutrition (2–4), and moderate-to-severe malnutrition (5–12). The correlations between the CONUT score and baseline characteristics and clinical indicators were evaluated. ResultsThis study ultimately included 5014 CRC patients. The nutritional status of patients with colon cancer (CC) was worse than that of rectal cancer (RC). The nutritional status was worse in men than in women. The older the patient, the poorer the nutritional status, and the poorer the nutritional status, the longer the hospital stay. In addition, poor nutritional status in patients is indicated by higher values of neutrophils (NE), monocytes (MC), eosinophils (EOS), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), carcinoembryogenic antigen (CEA), and lower values of white blood cells (WBC), basophils (BAS), haemoglobin (HB), total protein (TP), triglycerides (TG), low density lipoprotein (LDL), aspartate transaminase (AST), and blood urea nitrogen (BUN), which was statistically significant (P < 0.05). Indicators that significantly correlated with the CONUT score reflected the immune nutritional status, including WBC (odds ratio [OR] = 0.036, P < 0.001), NE (OR = 30.815, P < 0.001), MC (OR = 41.388, P < 0.001), EOS (OR = 27.577, P < 0.001), BAS (OR = 0.006, P = 0.046), and LDL (OR = 0.319, P < 0.001). ConclusionAdditional variables such as WBC, NE, MC, EOS, BAS, and LDL may be used as supplementary indicators in the CONUT scoring system to more effectively predict the clinical prognosis of CRC patients.

6-Parts Haematology Parameters Evaluation Using Abbott Alinity H

Nowadays, there are variety of automated hematology analyzers available in the market. However, the new product of diagnostic equipment should be evaluated and validated to ensure their capability. Thorough process of testing on all new hematology analyzers must be performed to certify that reliable result will be released and for patient safety. This study was carried out to evaluate automated hematology analyzers; Abbott Alinity H, in the Hospital Universiti Sains Malaysia setting. Blood samples send for complete blood count were selected randomly (n = 50) from healthy subjects and those who have different blood disorders. Blood specimens and quality control materials were analysed on the Abbott Alinity H to evaluate the precision. For correlation, the Sysmex XN-1000 was used as the comparative method. The study showed very good correlation between Abbott Alinity H and Sysmex, XN-1000 in the parameters such as white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), mean cell volume (MCV), platelet (PLT), neutrophil (NEU), lymphocyte (LYM), monocyte (MONO), eosinophil (EOS), and basophil (BASO). For the precision, all the parameters are performed well within allowable limits of performance for Abbott Alinity H. In conclusion, the Abbott Alinity H demonstrated an acceptable performance in term of precision and the analyzer was equivalent with the Sysmex XN-1000.

Effects of Dietary Calcium Lactate Supplementation on Laying Performance, Blood Index, Shinbone Quality, Jejunal Immunity, and Egg Quality of Aged Laying Hens

This study aimed to verify the potential of calcium lactate for the performance, blood index, shinbone quality, jejunal immunity, and egg quality of aged laying hens. A total of 360 62-week-old Hy-Line Brown laying hens were randomly divided into four treatments, with six replicates and 15 chickens per replicate. Experimental groups were fed with 0.25%, 0.5%, and 1.0% calcium lactate to substitute limestone in the control group (maintaining the same amount of calcium). The feeding trial lasted for 12 weeks. The laying rate and daily egg mass of laying hens fed the diets supplemented with calcium lactate was increased relative to those of the control group. The dietary addition of calcium lactate for laying hens enhanced the eggshell ratio, eggshell thickness, eggshell strength, and albumen height of eggs, and the addition level of 0.5% had the best effect. Dietary calcium lactate increased the number of red blood cells, corpuscular hemoglobin, mononuclear leucocytes and basophilic granulocytes, and decreased heterophils in the blood of laying hens. The activities of serum alanine transaminase and creatine kinase in laying hens was reduced by the dietary addition of calcium lactate. Calcium lactate supplementation in diets increased the serum calcium and phosphorus contents of laying hens. The dietary inclusion of calcium lactate increased the contents of IgA, IgG, lysozyme, and sIgA in the jejunal mucosa, and the 0.5% addition level worked best, but the IL-2 content decreased. The addition of 0.5% calcium lactate to the diet reduced the maximal force of the shinbone and increased the work required for shinbone rupture in laying hens. In conclusion, the dietary addition of calcium lactate improved the performance and egg quality of laying hens, probably by its positive effects on body health, intestinal digestible ability, calcium bioavailability, and jejunal mucosal immunity. The optimum amount of calcium lactate in the diet of laying hens is recommended to be 0.5%.

Coronavirus Receptor Expression Profiles in Human Mast Cells, Basophils, and Eosinophils.

A major problem in SARS-CoV-2-infected patients is the massive tissue inflammation in certain target organs, including the lungs. Mast cells (MC), basophils (BA), and eosinophils (EO) are key effector cells in inflammatory processes. These cells have recently been implicated in the pathogenesis of SARS-CoV-2 infections. We explored coronavirus receptor (CoV-R) expression profiles in primary human MC, BA, and EO, and in related cell lines (HMC-1, ROSA, MCPV-1, KU812, and EOL-1). As determined using flow cytometry, primary MC, BA, and EO, and their corresponding cell lines, displayed the CoV-R CD13 and CD147. Primary skin MC and BA, as well as EOL-1 cells, also displayed CD26, whereas primary EO and the MC and BA cell lines failed to express CD26. As assessed using qPCR, most cell lines expressed transcripts for CD13, CD147, and ABL2, whereas ACE2 mRNA was not detectable, and CD26 mRNA was only identified in EOL-1 cells. We also screened for drug effects on CoV-R expression. However, dexamethasone, vitamin D, and hydroxychloroquine did not exert substantial effects on the expression of CD13, CD26, or CD147 in the cells. Together, MC, BA, and EO express distinct CoV-R profiles. Whether these receptors mediate virus-cell interactions and thereby virus-induced inflammation remains unknown at present.

The Impact of Blood Morphological Parameters on Treatment Outcomes in Tennis Elbow Patients Receiving Platelet-Rich Plasma (PRP) Therapy: A Prospective Study.

Platelet-rich plasma (PRP) therapy holds substantial promise for the treatment of tennis elbow, a complex and challenging musculoskeletal condition. The aim of the study was to assess whether there are correlations between the levels of individual morphotic elements determined in whole blood and the outcomes of tennis elbow treatment with PRP injection, as measured using patient-reported outcome measures (PROMs) such as the Visual Analog Scale (VAS), Quick Disabilities of the Arm, Shoulder, and Hand (QDASH), and Patient-Rated Tennis Elbow Evaluation (PRTEE). A prospective analysis was conducted on 107 patients (132 elbows) undergoing lateral epicondylitis treatment with (PRP) injections. Patients completed VAS, PRTEE, and QDASH questionnaires on the day of PRP administration and at established checkpoints (2, 4, 8, 12, 24, 52, and 104 weeks). Minimal clinically important difference (MCID) was employed to assess the treatment effects. Then, correlations were measured within each PROM, and the impact of the concentration of individual blood parameters on the MCID outcomes was assessed. Analyzing the relationships between the MCID+ and MCID- groups, significant correlations for the VAS and QDASH scales were observed. The level of individual morphotic elements in the blood may have influenced the treatment outcome, as measured using specific patient-reported outcome measures (PROMs). Regarding the VAS scale, factors favoring a positive treatment outcome included higher values of eosinophils (EOS) and basophils (BASO). For the QDASH scale, these factors were a lower value of mean corpuscular volume (MCV) and a higher mean corpuscular hemoglobin (MCH). The levels of certain blood parameters, such as EOS and BASO, in the current study influenced the classification of patients into MCID+ or MCID- groups, based on the VAS and QDASH scales.

Lack of a transcriptional response of primary bronchial epithelial cells from patients with asthma and controls to IL-33.

IL-33 and IL-1RL1 are well-replicated asthma genes that act in a single pathway toward type-2 immune responses. IL-33 is expressed by basal epithelial cells, and the release of IL-33 upon epithelial damage can activate innate lymphoid cells, T helper-2 cells, basophilic granulocytes, and mast cells through a receptor complex containing IL-1RL1. However, it is unknown how bronchial epithelial cells respond to IL-33, and whether this response is increased in the disease. We aimed to characterize the IL-33-driven transcriptomic changes in cultured primary bronchial epithelial cells from patients with asthma and healthy controls. Primary bronchial epithelial cells (PBECs) were obtained by bronchial brushing from six healthy control for air-liquid interface (ALI) cultures, whereas we selected eight healthy controls and seven patients with asthma for epithelial organoid cultures. We then stimulated the cultures for 24 h with recombinant IL-33 (rhIL33) at various concentrations with 1, 10, and 50 ng/mL for the ALI cultures and 20 ng/mL and 100 ng/mL for the organoid cultures, followed by RNA-sequencing and differential gene expression analysis. We did not detect any genome-wide significant differentially expressed genes after stimulation of PBECs with IL-33, irrespective of growth in three-dimensional (3-D) epithelial organoids or after differentiation in ALI cultures. These results were identical between PBECs obtained from patients with asthma or from healthy control subjects. We detected very low levels of IL-1RL1 gene expression in these airway epithelial cell cultures. We conclude that bronchial epithelial cells do not have a transcriptional response to IL-33, independent of their differentiation state. Hence, the airway epithelium acts as a source of IL-33 but does not seem to contribute to the response upon release of the alarmin after epithelial damage.NEW & NOTEWORTHY The IL-33/IL-1RL1 pathway stands as a formidable genetic predisposition for asthma, with ongoing clinical developments of various drugs designed to mitigate its influence in patients with asthma. The absence of a transcriptomic reaction to IL-33 within the bronchial epithelium holds significance in the pursuit of identifying biomarkers that can aid in pinpointing those individuals who would derive the greatest benefit from therapies targeting the IL-33 pathway.

Clinical and Genetic Features By Next-Generation Sequencing and RNA Sequencing in Pre-Fibrotic Primary Myelofibrosis Patients

The 2016 WHO classification recognized pre-fibrotic primary myelofibrosis (pre-PMF) as a distinct entity. Such knowledge is essential to depict the landscape of pre-PMF and develop mechanism-based approaches to slow the progression of pre-PMF. Here, we conducted a retrospective study of 234 pre-PMF patients defined by 2016 WHO diagnostic criteria in 13 hematooncology centers between 01 January 2015 and 31 July 2023 (ChiCTR2200061208). We evaluated clinical characteristics, risk factors and genetic features of progression to overt-PMF in pre-PMF patients. Among 234 pre-PMF patients, 135 (57.7%) harbored JAK2V617F, 36 (15.4%) CALR and 3 (1.3%) MPL mutations; 60 (25.6%) patients were negative for all three mutations. JAK2V617F-mutated patients were older ( P=0.036), had more constitutional symptoms ( P=0.027) and cardiovascular risk factors ( P=0.045), higher white blood cell count (WBC) ( P&amp;lt;0.001), hemoglobin level (HB) ( P&amp;lt;0.001), neutrophile granulocyte (NEU) ( P&amp;lt;0.001), eosinophilic granulocyte (EOS) ( P&amp;lt;0.001), basophilic granulocyte (BAS) ( P&amp;lt;0.001), hematocrit (HCT) ( P=0.002) and red blood cell distribution width (RDW) ( P&amp;lt;0.001) (Figure A). CALR-mutated cases had higher platelet hematocrit (PCT) ( P=0.043) and lactic dehydrogenase (LDH) ( P=0.008). Besides, CALR group had a higher proportion of 25.0% to progress to overt-PMF than JAK2V617F group (9.6%) and TN group (6.7%) ( P=0.025) (Figure A). As for risk factors of progression to overt-PMF, univariable analysis found it was associated with mean platelet volume (MPV) ( P=0.019), HB ( P=0.027), WBC ( P=0.008), LDH ( P=0.004) and CALR mutations ( P=0.007). Multivariable analysis revealed that lower HB value ( P=0.041; HR 0.981, 95% CI 0.962-0.999) and CALR mutation ( P=0.001; HR 3.716, 95% CI 1.331-10.069) had negative impact on the progression to overt-PMF (Figure B). When divided by HB with cut-off point of 128 g/L, patients with HB value ≤128 g/L were more likely to progress to overt-PMF compared to &amp;gt;128 g/L groups ( P=0.007) (Figure C). And patients carried CALR mutation were also more likely to progress to overt-PMF ( P&amp;lt;0.001) (Figure D). We performed next-generation sequencing (NGS) in 18 pre-PMF patients, including 9 JAK2V617F, 3 CALR and 6 TN, 3 of which progressed to overt-PMF and 15 stayed in pre-PMF until the end of the follow-up. JAK2V617F was the most frequently mutated gene (9/38, 23.7%), followed by TET2 (7/38, 18.4%), RELN (4/38, 10.5%) and ASXL1 (3/38, 7.9%). JAK2V617F-mutated patients possessed more mutations related to activation signaling pathway ( P=0.025) and DNA methylation ( P=0.033) (Figure F). TN patients possessed more mutations related to transcription factor ( P=0.048) (Figure F). Patients who progressed to overt-PMF possessed more mutations associated with myeloid related transcription factor ( P=0.025) (Figure H). We further performed RNA-Seq analysis in 6 pre-PMF samples and 14 overt-PMF samples. Compared to pre-PMF, overt-PMF showed 49 up-regulated and 13 down-regulated differentially expressed genes (DEGs), of which CSCF3 and CXCL13 were significantly up-regulated (Figure I,J). Gene ontology (GO) functional enrichment analysis showed that DEGs were enriched in cell-cell signaling, cytokine activity, monocyte chemotaxis and chemokine activity (Figure K). KEGG biofunctional analysis showed that DEGs were significantly enriched in cytokine-cytokine receptor interaction, chemokine signaling pathway, IL-17 signaling pathway and NF-kappa B signaling pathway (Figure L). In conclusion, CALR-mutated pre-PMF patients with HB value ≤128 g/L were more likely to progress to overt-PMF. Genetic analysis found patients with high proportion of progress to overt-PMF tended to possess mutations associated with myeloid related transcription factor. And the upregulation of CSCF3 and CXCL13 may potentially drive the progression of overt-PMF in pre-PMF patients through inflammatory and cytokine related pathways. Acknowledgement: This research was funded by the Key R&amp;D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; Zhejiang Medical Association Clinical Medical Research special fund project, No. 2022ZYC-D09. *Correspondence to: Jian Huang, M.D., Ph.D., Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, China. E-mail: househuang@zju.edu.cn

Association between ambient air pollution exposure in pregnant women with antiphospholipid syndrome in Nanjing, China

Antenatal exposure to air pollutants is thought to be associated with a variety of maternal blood markers as well as adverse birth outcomes. However, the dysgenic influence of air pollutants on the antiphospholipid syndrome (APS) in mothers and their pregnancy outcomes remains unclear. In the current study, 371 mother-infant pairs (189 healthy: 182 APS) from Nanjing Maternal and Child Health Hospital as well as air pollutants concentration from their living environment were used to investigate correlations between air pollution with maternal blood indicators and fetal birth weight in the groups of APS and healthy mothers. Generalized linear model was used to evaluate the contributions of air pollutant exposure during pregnancy to the blood indicators variation. The relationships between birth weight with specific air pollutant and blood index were analyzed using ridge regression. Results showed that APS fetal birth weight was significantly impacted by air pollutant exposure during pregnancy, in particular, the birth weight decreased significantly along with increasing fine particulate matter 2.5 (PM2.5) and fine particulate matter 10 (PM10) exposure concentrations throughout pregnancy. In contrast, birth weight increased significantly with sulfur dioxide (SO2) exposure. In addition, APS-related blood indicators comprised of platelet distribution width (PDW), total bilirubin (TBIL), mean platelet volume (MPV), platelet-larger cell ratio (P_LCR), homocysteine (HCY), alkaline phosphatase (ALP), direct bilirubin (DBIL), basophilic granulocyte (BAS), platelet thrombocytocrit (PCT), preprandial glucose levels (OGTT0), monocytes (MON), and monocytes ratio (MON_ratio) were also strongly related with prenatal exposure to PM2.5 and PM10, in which PDW levels showed most strongly negative impaction on fetal birth weight. Together, we showed that prenatal exposure to air pollutant (PM2.5 and PM10) may exacerbate the poor birth outcomes of low birth weight by impacting APS maternal blood indicators especially for PDW.

Chronic spontaneous urticaria—status quo and future

AbstractChronic spontaneous urticaria (CsU) is a chronic inflammatory dermatosis whose etiology is not yet fully understood. In affected patients, it is often associated with a high limitation of health-related quality of life, which necessitates effective therapeutic management. Different immune cell populations such as mast cells, eosinophilic and basophilic granulocytes, and T cells are involved in the pathogenesis of CsU, whereby mast cells playing a key role. In addition, type I autoallergic reactions with auto IgE antibodies or type IIb autoimmune reactions with auto IgG antibodies have been identified in a proportion of patients. The current international guideline initially recommends the use of second-generation H1 antihistamines, first in standard, then in off-label quadruple dosing. Subsequently, the anti-IgE antibody omalizumab should be added. However, this therapy algorithm does not lead to freedom from manifestations in all patients. Therefore, various targeted therapies are currently being evaluated for their efficacy in CsU, such as off-label use of the anti-interleukin receptor alpha (IL4Rα) antibody dupilumab, the anti-IL-17A antibody secukinumab, or interleukin‑5 blockade using mepolizumab, reslizumab, or benralizumab. In addition, new promising compounds such as the Bruton tyrosine kinase (BTK) inhibitors remibrutinib and fenebrutinib, the anti-cKIT antibody barzolvolimab, the anti-SIGLEC8 antibody lirentelimab, the anti-TSLP antibody tezepelumab, the anti-C5aR1 antibody advoralimab, or the topical application of Syk kinase inhibitors are being tested, which were developed according to new insights into the pathogenesis of CsU. The BTK inhibitor fenebrutinib is currently not being pursued due to a less favorable side effect profile compared to remibrutinib, as well as the anti-IgE antibody ligelizumab, which was inferior to omalizumab therapy in a phase 3 study. Overall, there is a high need for new therapeutic strategies to better treat CsU both symptomatically and curatively. This requires a more comprehensive understanding of pathogenesis of the disease in order to develop new targeted therapies.

The effects of acutely elevated ammonia concentrations on haemolymph parameters in the Mediterranean mussel, Mytilus galloprovincialis

In aquaculture systems, ammonia nitrogen is a major component of waste products arising from the metabolism of cultured organisms and can significantly affect the quality of the rearing environment. The purpose of the current study was to determine modulation of the haemocyte population and selected haemolymph biochemical parameters of the Mediterranean mussel Mytilus galloprovincialis (Lamarck, 1919) exposed to acutely elevated ammonia concentrations.In order to investigate the extent and dynamics of an expected reduction of physiological fitness and survival rate of cultured mussels the stress-on-stress test was conducted combining ammonia and air exposure. The latter test illustrated the extent of reduced mussel physiological fitness and survival rate upon 72 h exposure to 10 and 30 mM NH4Cl in experimental tanks followed by additional exposure to air. Mussels cultured for up to 48 h in experimental tanks comprising 5, 10 and 30 mM NH4Cl, revealed dose and time dependent increase in haemolymph enzyme lactate dehydrogenase levels, urea, and uric acid metabolite levels, as well as the corresponding redistribution in haemocyte population profiles, indicating an inherent response of this organism to ammonia. Finally, a significant negative linear correlation between the mussel hyalinocytes subpopulation and the mean urea levels was observed. The obtained result suggests a possible function of basophilic and acidophilic granulocyte subpopulations in ammonia metabolism leading to urea synthesis by means of surplus ammonium ions are sequestered and extracted from the body. Therefore, defined modulation of the mussel haemocyte population structure may serve as an accurate bioindicator of mussels exposure to acutely elevated ammonia concentrations in environmental and aquaculture biomonitoring studies.

Morphometric parameters of pelvic lymph nodes in experimental metastatic prostate cancer

The study purpose. Identification of structural and functional changes in pelvic lymph nodes in experimental metastatic prostate cancer. Materials and methods. The study included 30 male mice aged 3 months. All animals ( n = 30) were divided into 2 groups. The first group (the main one, n = 20) included mice that had a model of metastatic prostate cancer created by transplanting an Ehrlich tumor into the prostate parenchyma. These animals were further divided into two equal subgroups: 1a ( n = 10) – mice were withdrawn from the experiment on day 7; 1b ( n = 10) – mice were withdrawn from the experiment on day 18. The second group ( n = 10) included mice that were not manipulated, they made up the control group. After the end of the experiment, morphological analysis of the prostate gland and regional (pelvic) lymph nodes in mice of both groups was performed using light microscopy. Statistical processing of the results was carried out using the Statistica 8.0 software package. The differences were considered statistically significant at p &lt; 0.05. Results. When compared to the control group the mice of groups 1a and 1b, the prostate parenchyma was almost completely replaced by atypical cells, which demonstrates the presence of neoplastic processes in the prostate gland. In group 1a mice, the number of pelvic lymph nodes was 1.9 times as large, and in group 1b animals, this indicator was 2.7 times higher compared to the second group ( p &lt; 0.01). In animals of the first group, the proportion of mast cells in the pelvic lymph nodes increased by 121 % compared to the control group ( p &lt; 0.01). At the same time, we revealed a direct relationship of mast cells with the number of tumor cells and immunoblasts in the medullar sinuses, which indicates the participation of tissue basophils in tumor metastasis. We also recorded a significant increase in the area of the medullar sinuses of regional lymph nodes in animals of groups 1a by 12.4 % ( p &lt; 0.05) and 1b by 20.2 % ( p &lt; 0.01) against the background of an increase in the number of mast cells in this zone compared to the control group, which indicates the possible participation of mast cells in lymphangiogenesis. Conclusion. Mast cells can potentially play a role in the development of malignant neoplasms of the prostate gland. The number of mast cells increases in pelvic lymph nodes in animals with a created model of metastatic prostate cancer. The obtained direct dependence of the increase in the number of mast cells and the increase in the number of tumor cells with immunoblasts suggests the participation of tissue basophils in the spread of metastases. It can be assumed that infiltration of lymph nodes by mast cells may correlate with a poor prognosis of prostate cancer, since these granulocytes contribute to tumor metastasis.

Perioperative aspects of anaphylaxis

Anaphylaxis is a generalized, severe, life-threatening reaction, mostly with an allergic origin. Triggers are usually drugs, insect bites, poisons, contrast material and food. It is caused by various mediators (histamine, prostaglandins, leukotrienes etc.) released from mast cells, basophilic granulocytes. Histamine plays a central role in its creation. Immediate recognition and specific treatment instantaneously are essential for successful treatment. In severe conditions, the clinical features are very similar, regardless of their allergic/non-allergic origin. The incidence can vary over time and between patient populations. Its incidence is extremely variable, approximately 1/10000 anaesthesia. Most studies cite neuromuscular blocking agents as the most common causative factor. In England, the results of the 6th National Audit Project revealed that the most common causes were antibiotics (1/26845), followed by neuromuscular junction blocking drugs (1/19070), chlorhexidine (1/127698), and Patent Blue paint (1/6863). It occurs within 5 minutes in 66% of cases, 6-10 minutes in 17%, 11-15 minutes in 5%, 16-30 minutes in 2%, but usually within 30 minutes. Antibiotic allergy is a growing problem, especially to teicoplanin (16.4/100000) and co-amoxiclav (8.7/100000). The risk of anaphylactic shock should not be a determining factor in choosing the type of muscle relaxant drug. The patient's anaesthesia classification, physical condition, obesity, use of beta-blockers and ACE inhibitors influence the clinical characteristics. The initial symptoms can be extremely varied in terms of the effectiveness of the treatment, early recognition and commencement of therapy are the keys to success. Asking about a preoperative allergy history can reduce the risk and incidence of anaphylaxis. Orv Hetil. 2023; 164(22): 871-877.

Pathophysiological aspects of the mechanisms of action of osteotropic drugs in an in vitro experiment on the blood mononuclear cells of patients with frontal bone injuries

Relevance: Pathogenetic treatment of head injuries should be based on the development of post-traumat ic disease, including the role of immune reactions in bone matrix regeneration processes. Repair of bone structures depends on activating stimuli from cells of the immune system. Currently, there is research on the importance of vitamin D in metabolic processes in mesenchymal tissue that affect the formation of the bone matrix and general mineralization of bones, as well as the drug osteogenon, the basis of which are ossein-hydroxyapatite compounds, which stimulate local regulators of bone tissue remodelling and calcium-phosphorus metabolism. Taking into account these data, it will be appropriate to determine the effect of drugs on the processes of bone tissue regeneration in patients with injuries of the frontal bone. Purpose: to determine the effect of various drugs used in the treatment of frontal skull injuries on the pathophysiological mechanisms of inflammation (interleukin-1β, interleukin-10, γ-interferon), stabilization of cell membranes, and the level of regenerative cytokines. Materials and methods: The authors conducted immunological studies on the determination of cytokine factors of inflammation and regeneration in 29 patients with frontal bone injury under the influence of various osteotropic drugs: ossein-hydroxyapatite compounds, osteogenon and vitamin D3 (water-soluble form – aquadetrim), both individually and in combination with each other. The research was carried out in an in vitro experiment in RPMI-1640 medium (Serva, Germany) with blood mononuclear cells from patients. γ-interferon), anti-inflammatory regeneration factor (transforming growth factor-TGF-1β). In the conditions of the experiment, the membrane-protective properties of the above-mentioned osteotropic drugs were investigated on cultures of peritoneal tissue basophils under the conditions of using protamine sulfate as a damaging factor. Results and discussion: it was established that osteogenon and aquadetrim (vit. D3) have a positive effect on the production of cytokines by mononuclear cells in the blood of patients with TLC: they reduce the level of in vitro pro-inflammatory production and increase the production of anti-inflammatory cytokines, especially when used together. Protamine sulphate (liberator) was able to destroy 61% of tissue basophils, SK and osteogenon reduced this percentage, but not reliably. Reliable data were obtained under the action of vitamin, and combinations of ossein-hydroxyapatite compounds + vitamin and osteogenon + vitamin (р=0.01). The use of a general mixture of all drugs did not cancel the effect of liberation of TB. It can be assumed that the main membrane protector is vitamin D3 in the form of a water-soluble form – aquadetrim, which has various directions of pathophysiological influence on the mechanisms of inflammation and regeneration. Conclusions: The growth factor was better stimulated with a mixture of all drugs (~1.7 μg/ml) in combination with vitamin D3. Membrane-protective properties were better expressed under the action of vitamin D3 and combinations of osseinhydroxyapatite compounds + vitamin D3 and osteogenon + vitamin D3. The most effective in activating immunocompetent blood cells were combinations of osteotropic drugs that reduced the level of proinflammatory cytokines and increased the content of anti-inflammatory interleukin-10 in the culture fluid.

Hematological Indices of Experimental Rats Fed with Rat Chow Fortified with Processed Breadfruits

Background: The abundance of nutrients, vitamins, and fiber in breadfruit has been documented in many literature studies that can hardly be exhausted and are consumed majorly by the Igbos and other southern parts of Nigeria to ameliorate hunger.&#x0D; Aim: This study however was aimed at determining the effect of feeds fortified with grilled, preboiled, and cooked breadfruit on hematological indices of wistar rats.&#x0D; Methods: Hematological parameters were determined using an automated hematology analyzer (Mindray-BC-5300). The parameters analyzed include Hemoglobin (HGB), Packed Cell Volume (PCV), Red Blood Cells (RBC), Platelets (PLT), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), White Blood Cells (WBC), Neutrophils (NEUT), Lymphocytes (LYMPH), Monocytes (MON), Eosinophils (EOS) and Basophils (BAS).&#x0D; Results: The result from the experiment indicated that all fortified groups showed no significant increase or decrease (p&gt;0.05) in their HGB, PCV, RBC, PLT, MCV, MCH and MCHC when compared with their respective controls. The white blood cell, neutrophil and eosinophil concentrations of the experimental rats significantly increased (p&lt;0.05) compared with the normal control group. A significant decrease (p&lt;0.05) was observed in the lymphocyte and basophil concentration. The monocyte levels of the experimental rats showed a non-significant increase or decrease (p&gt;0.05) in all the groups with respect to the normal control.&#x0D; Conclusion: It may however be safe to infer that fortification of feed with breadfruit has no negative effect on the physiological status of the experimental animals as all the hematological parameters remained within range.