Pulmonary delivery of silver nanoparticles prevents influenza infection by recruiting and activating lymphoid cells.

Silver nanoparticles (AgNPs) are a potential antiviral agent due to their ability to disrupt the viral particle or alter the virus metabolism inside the host cell. In vitro, AgNPs exhibit antiviral activity against the most common human respiratory viruses. However, their capacity to modulate immune responses during respiratory viral infections has yet to be explored. This study demonstrates that administering AgNPs directly into the lungs prior to infection can reduce viral loads and therefore virus-induced cytokines in mice infected with influenza virus or murine pneumonia virus. The prophylactic effect was diminished in mice with depleted lymphoid cells. We showed that AgNPs-treatment resulted in the recruitment and activation of lymphocytes in the lungs, particularly natural killer (NK) cells. Mechanistically, AgNPs enhanced the ability of alveolar macrophages to promote both NK cell migration and IFN-γ production. By contrast, following infection, in mice treated with AgNPs, NK cells exhibited decreased activation, indicating that these nanoparticles can regulate the potentially deleterious activation of these cells. Overall, the data suggest that AgNPs may possess prophylactic antiviral properties by recruiting and controlling the activation of lymphoid cells through interaction with alveolar macrophages.

Expression profile of microRNAs in bovine lymphocytes infected with Theileria annulata and treated with buparvaquone.

Several miRNA-based studies on Theileria-transformed bovine cells have been conducted; however, the mechanism by which transformed cells exhibit uncontrolled proliferation is not yet fully understood. Therefore, it is necessary to screen more microRNAs that may play a role in the transformation process of host cells infected with Theileria annulata to better understand the transformation mechanisms of Theileria-infected cells. RNA sequencing was used to analyze miRNAs expression in the host bovine lymphocytes infected with T. annulata at different time points after buparvaquone (BW720) treatment and DMSO treatment (control groups). Differential miRNAs related to cell proliferation and apoptosis were identified through comparison with gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and a regulatory network of miRNA-mRNA was constructed. In total, 272 differentially expressed miRNAs were found at 36, 60 and 72 h. The miRNAs change of bta-miR-2285t, novel-miR-622, bta-miR-2478, and novel-miR-584 were significant. Analysis of 27 of these co-differential expressed miRNAs revealed that 15 miRNAs were down-regulated and 12 miRNAs were up-regulated. A further analysis of the changes in the expression of each of these 27 miRNAs in the three datasets suggested that bta-miR-2285t, bta-miR-345-5p, bta-miR-34a, bta-miR-150, and the novel-miR-1372 had significantly changed. Predicted target genes for these 27 miRNAs were analyzed by KEGG and the results demonstrated that EZR, RASSF, SOCS1 were mainly enriched in the signaling pathway microRNAs in cancer. MAPKAPK2, RELB, FLT3LG, and GADD45B were mainly enriched in the MAPK signaling pathway, and some genes were enriched in Axon guidance. This study has provided valuable information to further the understanding of the regulatory function of miRNAs in the host microenvironment and host-parasite interaction mechanisms.

Neutrophil-to-lymphocyte ratio as a predictor of cardiovascular mortality in cancer survivors.

This study aims to evaluate the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker for cardiovascular mortality among cancer patients, utilizing data from the National Health and Nutrition Examination Survey (NHANES). From the NHANES dataset (2007-2018), we analyzed 4974 cancer survivors, investigating the prognostic significance of NLR for all-cause, cardiovascular, and cancer-specific mortality. Survival outcomes were analyzed using Cox regression and Kaplan-Meier methods. Optimal NLR cutoffs were identified as 2.61 for differentiating the higher NLR group from lower NLR group. Elevated NLR levels significantly correlated with increased all-cause mortality (HR 1.11, 95% CI 1.07-1.14, P < 0.001) and cardiovascular mortality (HR 1.14, 95% CI 1.08-1.21, P < 0.001) in adjusted models. Subgroup analyses revealed that age, sex, smoking status, and hypertension significantly influence NLR's association with cardiovascular mortality. Specific cancers including breast, prostate, non-melanoma skin, colon and melanoma experience increased all-cause and cardiovascular mortality in the higher NLR group compared to lower NLR group. Elevated NLR is a significant predictor of increased mortality in cancer patients, particularly for cardiovascular outcomes. These findings support that NLR acts as a pivotal prognostic tool with significant implications for clinical practice in the realm of cardio-oncology.

Relationship between platelet-to-lymphocyte ratio and early rebleeding after endoscopic variceal ligation: a bicenter retrospective study.

BACKGROUND: Endoscopic variceal ligation (EVL) is the primary treatment for esophageal variceal bleeding in patients with liver cirrhosis (LC). Postoperative rebleeding is a complication of EVL, contributing to over 20% of bleeding-related deaths. This study aims to examine the association between platelet-to-lymphocyte ratio (PLR) and rebleeding within 6 weeks after EVL in patients with LC. METHODS: The study included 145 eligible patients who underwent their first EVL procedure at Yijishan Hospital of Wannan Medical College between January 2016 and August 2022 (YJS cohort). An external validation cohort comprising 338 eligible patients from NO.2 People's Hospital of Fuyang City (FY cohort) between July 2018 and August 2022 was also utilized. RESULTS: In the YJS cohort, Multivariate logistic analysis indicated that high PLR is independently associated with early rebleeding after EVL. The restricted cubic spline analysis demonstrated that the risk of rebleeding increases with rising PLR, stabilizing at PLR values greater than 150. Similar findings were validated in the FY cohort. CONCLUSIONS: Our results have the potential to aid in the identification of high-risk patients for early rebleeding after EVL, thereby enabling improved clinical management and outcomes for these individuals.

This study is the first to report on the independent association between the platelet-to-lymphocyte ratio (PLR) and early rebleeding after endoscopic variceal ligation (EVL).The restricted cubic spline analysis showed a linear correlation between PLR and the risk of early rebleeding after EVL.An increase in PLR level is independently associated with a higher risk of early rebleeding after EVL.

TCF-1 and TOX regulate the memory formation of intestinal group 2 innate lymphoid cells in asthma.

Immune memory has been expanded to group 2 innate lymphoid cells (ILC2s), but the cellular and molecular bases remain incompletely understood. Based on house dust mite (HDM)-induced mice asthma models and human samples, we applied flow cytometry, parabiosis, in vivo imaging and adoptive transplantation to confirm the persistence, migration and function of CD45+lineage-CD90.2+NK1.1-NKp46-ST2-KLRG1+IL-17RB+ memory-like ILC2s (ml-ILC2s). Regulated by CCR9/CCL25 and S1P signaling, ml-ILC2s reside in the lamina propria of small intestines (siLP) in asthma remission, and subsequently move to airway upon re-encountering antigens or alarmins. Furthermore, ml-ILC2s possess properties of longevity, potential of rapid proliferation and producing IL-13, and display transcriptional characteristics with up-regulation of Tox and Tcf-7. ml-ILC2s transplantation restore the asthmatic changes abrogated by Tox and Tcf7 knockdown. Our data identify siLP ml-ILC2s as a memory-like subset, which promotes asthma relapse. Targeting TCF-1 and TOX might be promising for preventing asthma recurrence.

Predictive value of near-term prediction models for severe immune-related adverse events in malignant tumor PD-1 inhibitor therapy.

Immune-related adverse events (irAEs) impact outcomes, with most research focusing on early prediction (baseline data), rather than near-term prediction (one cycle before the occurrence of irAEs and the current cycle). We aimed to explore the near-term predictive value of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), absolute eosinophil count (AEC) for severe irAEs induced by PD-1 inhibitors. Data were collected from tumor patients treated with PD-1 inhibitors. NLR, PLR, and AEC data were obtained from both the previous and the current cycles of irAEs occurrence. A predictive model was developed using elastic net logistic regression Cutoff values were determined using Youden's Index. The predicted results were compared with actual data using Bayesian survival analysis. A total of 138 patients were included, of whom 47 experienced grade 1-2 irAEs and 18 experienced grade 3-5 irAEs. The predictive model identified optimal α and λ through 10-fold cross-validation. The Shapiro-Wilk test, Kruskal-Wallis test and logistic regression showed that only current cycle data were meaningful. The NLR was statistically significant in predicting irAEs in the previous cycle. Both NLR and AEC were significant predictors of irAEs in the current cycle. The model achieved an area under the ROC curve (AUC) of 0.783, with a sensitivity of 77.8% and a specificity of 80.8%. A probability ≥ 0.1345 predicted severe irAEs. The model comprising NLR, AEC, and sex may predict the irAEs classification in the current cycle, offering a near-term predictive advantage over baseline models and potentially extending the duration of immunotherapy for patients.

Recruitment of CXCR4+ type 1 innate lymphoid cells distinguishes sarcoidosis from other skin granulomatous diseases.

Sarcoidosis is a multiorgan granulomatous disease that lacks diagnostic biomarkers and targeted treatments. Using blood and skin from patients with sarcoid and non-sarcoid skin granulomas, we discovered that skin granulomas from different diseases exhibit unique immune cell recruitment and molecular signatures. Sarcoid skin granulomas were specifically enriched for type 1 innate lymphoid cells (ILC1s) and B cells and exhibited molecular programs associated with formation of mature tertiary lymphoid structures (TLSs), including increased CXCL12/CXCR4 signaling. Lung sarcoidosis granulomas also displayed similar immune cell recruitment. Thus, granuloma formation was not a generic molecular response. In addition to tissue-specific effects, patients with sarcoidosis exhibited an 8-fold increase in circulating ILC1s, which correlated with treatment status. Multiple immune cell types induced CXCL12/CXCR4 signaling in sarcoidosis, including Th1 T cells, macrophages, and ILCs. Mechanistically, CXCR4 inhibition reduced sarcoidosis-activated immune cell migration, and targeting CXCR4 or total ILCs attenuated granuloma formation in a noninfectious mouse model. Taken together, our results show that ILC1s are a tissue and circulating biomarker that distinguishes sarcoidosis from other skin granulomatous diseases. Repurposing existing CXCR4 inhibitors may offer a new targeted treatment for this devastating disease.

Killing of xenogenous and virally infected homogenous target cells by shrimp lymphocyte-like haemocytes.

Haemocytes play a crucial role in the invertebrate's immune system. In our lab, five subpopulations of shrimp haemocytes were identified in the past: hyalinocytes, granulocytes, semi-granulocytes and two subpopulations of non-phagocytic cells. In the latter two subpopulations, their characteristics such as having small cytoplasmic rims and not adhering to plastic cell-culture plates are very similar to those of mammalian lymphocytes. Therefore, they were designated lymphocyte-like haemocytes. Although little is known about their function, we hypothesize, based on their morphology, that they may have a cytotoxic activity like natural killer cells, with the ability to recognize and kill target cells. In our study, K562 cells and Sf9 cells were used as xenogenous target cells to detect the cytotoxic activity of the shrimp non-adherent lymphocyte-like haemocytes. Non-adherent haemocytes were collected and mixed with K562 cells and Sf9 cells at a 5:1 ratio and the binding activity was examined under a microscope. The binding rate of non-adherent haemocytes to K562 cells and Sf9 cells reached 6.6 % and 2.4 % after 240 min of culture, respectively. Then, the killing activity of non-adherent haemocytes was detected by an EMA staining (fluorescence microscopy), which showed 3.75 % dead K562 cells and 1.025 % dead Sf9 cells, and by Sytox® blue staining (flow cytometry), which showed 4.97 % of dead K562 cells. Next, a killing assay was developed to visualize the killing activity of shrimp non-adherent haemocytes. Non-adherent haemocytes were pre-labeled in blue (CellTracker blue) and K562/Sf9 cells in green (CFSE); dead cells were differentially stained red with ethidium bromide. The cytotoxic activity increased and reached a level of 2.59 % in K562 cells and 0.925 % in Sf9 cells at 120 min after co-culture. Furthermore, in the co-cultures of non-adherent haemocytes with K562 cells and Sf9 cells, upregulation of the gene and protein expression of the cytotoxic molecules torso-like protein and granzyme B was observed by RT-qPCR at 240 min and western blotting at 180 min. Additionally, non-adherent haemocytes were co-cultured with WSSV-inoculated shrimp ovary and lymphoid organ cells to detect the cytotoxicity to homogenous target cells. The binding activity started at 60 min in both the ovary and lymphoid organ cultures and reached at 240 min 50.62 % and 40.7 %, respectively. The killing activity was detected by EMA staining and the percentage of dead ovary and lymphoid organ cells increased respectively from 10.84 % to 6.89 % at 0 min to 13.09 % and 8.37 % at 240 min. In conclusion, we demonstrated the existence of cytotoxic activity of shrimp lymphocyte-like haemocytes against xenogenous cells from mammals and insects and against WSSV-infected homogenous shrimp cells.

Application of neutrophil to lymphocyte ratio in ankylosing spondylitis: Based on bibliometric and visualization analysis.

Ankylosing spondylitis (AS) as a autoimmune disease involves inflammatory responses in the development of the disease, often causing changes in the neutrophil to lymphocyte ratio (NLR). In the past few decades, research on the relationship between NLR and AS has generally shown an upward trend. This study adopts the bibliometrics method to analyze the development trend, frontier, and hotspots of global research in this field in the past 2 decades. By searching for publications in the SCI-Expanded edition of the Web of Science Core Collection, the information of literature published between 2000 and 2023 is recorded. Based on the VOSviewer, CiteSpace and Excel, bibliometric analysis, and visualization analysis are conducted on the overall distribution of annual output, leading countries, active institutions, journals, authors, co-cited references, and keywords. Through retrieving and screening, a total of 1654 papers are obtained for analysis. In the past 2 decades, the number of publications related to this field has shown an increasing trend. The United States has the highest Hirsch index (H-index) and publication volume. The most productive institution is Harvard University, while the H-index of the University of Milan in Italy is far ahead. Frontiers in Immunology is the institution with the highest output. The H-index of the Annals of the Rheumatic holds the top position. This study has uncovered the main emphasis on NLR in AS research and has provided clarification regarding the value of NLR as a biomarker for immune inflammatory response in the diagnosis and prognosis of AS.

T lymphocyte and neutrophil/lymphocyte ratio in patients with radiation-induced oral mucositis after intensity-modulated radiation therapy for head and neck cancer: A retrospective single-center study.

To investigate T lymphocyte, neutrophil/lymphocyte ratio (NLR) and their impact on patients with radiation-induced oral mucositis (RIOM) after intensity-modulated radiotherapy for head and neck cancer. The clinical data of 148 patients diagnosed with head and neck cancer from January 2016 to January 2019 were retrospectively analyzed. Patients were divided into RIOM group (n = 42 cases) and non-RIOM group (n = 106 cases), based on whether they developed RIOM after intensity-modulated radiation therapy. The T lymphocyte and NLR of the 2 groups were analyzed before and after treatment; The correlation between T lymphocyte and NLR in RIOM group was analyzed. We used RTOG grading system to evaluate and scale the RIOM. The relationship between the grade of RIOM, T lymphocyte and NLR in RIOM group was analyzed. After treatment, the proportion of CD3 +, CD4 +, and CD8 + T lymphocytes in the 2 groups after treatment were decreased, and the RIOM group was significantly lower than non-RIOM group, P < .05. NLR in RIOM group was significantly higher than that in non-RIOM group, P < .05. The data of overall survival showed no significant differences between 2 groups (HR = 0.82, 95% CI: 0.43-1.59). Compared with RIOM group, patients in non-RIOM group showed a longer progress-free survival (HR = 0.57, 95% CI: 0.33-0.99). In RIOM group, NLR was negatively correlated with CD3 + (r = -0.433, P = .004), CD4 + (r = -0.644, P < .001) and CD8 + T cells (r = -0.665, P < .001). RIOM was positively correlated with NLR (R = 0.621, P < .001), negatively correlated with CD4 + T cell ratio (r = -0.449, P = .003) and CD8 + T cell ratio (r = -0.307, P = .048), but RIOM did not correlate with CD3 + T cell ratio (r = -0.225, P = .152). For patients with RIOM after intensity-modulated radiotherapy for head and neck cancer, T lymphocyte showed a downward trend, and NLR showed an upward trend. In addition, T lymphocyte and NLR are closely related to the RIOM, indicating that clinicians should be aware of the importance of T lymphocyte and NLR on patients received radiotherapy.

Correlation Between Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio with Risk Stratification Indicators and Thrombus Burden in Patients with Moderate-to-High Risk Acute Pulmonary Embolism, and Changes After Treatment.

OBJECTIVE: To investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and risk stratification indicators as well as thrombus burden in patients with moderate-to-high risk acute pulmonary embolism (APE), and to assess the changes in these parameters following interventional therapy. METHODS: This study retrospectively included patients with moderate-to-high risk APE who were admitted to the Department of Interventional Vascular Surgery at Putian First Hospital from May 2020 to May 2024. All patients received anticoagulation therapy, pulmonary artery catheter-directed thrombolysis, and/or mechanical thrombectomy. Patients were further divided into subgroup A if they did not present with any of the following conditions at admission: a) acute inflammatory diseases (including lung infections); b) malignant tumors; c) history of trauma or surgery within the past 2 months. Patients with any of the aforementioned conditions were classified as subgroup B. Additionally, 50 healthy individuals were randomly selected as the healthy control group. RESULTS: The NLR and PLR in subgroup A were significantly lower than those in subgroup B (P < .01). Compared with the healthy control group, the NLR in the APE group and subgroup A was significantly higher (P < .001). There were no significant differences in NLR and PLR between the troponin I-negative and troponin I-positive groups (P > .05), or between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-negative and NT-proBNP-positive groups (P > .05). There were no significant correlations between NLR and PLR with risk stratification indicators and pulmonary artery embolism index (P > .05). Compared with before treatment, NLR, troponin I, NT-proBNP, right ventricular diameter/left ventricular diameter ratio, and pulmonary artery embolism index were significantly reduced after treatment (P < .05), while there was no significant difference in PLR before and after treatment (P > .05). CONCLUSION: Elevated NLR in patients with APE, which decreases after effective treatment, may be used for assessing disease status and treatment efficacy. However, there is no correlation between NLR and risk stratification indicators or thrombus burden. PLR does not demonstrate significant value in assessing APE.

Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in diagnosing neonatal sepsis.

Clinical manifestations of neonatal sepsis are often unspecified. Therefore, sepsis biomarkers could be used to support diagnosis while waiting for blood culture results, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). The aim of this study was to evaluate the role of NLR and PLR as diagnostic markers in neonatal sepsis. A cross-sectional study was conducted at Haji Adam Malik General Hospital, Medan, Indonesia, from April to October 2019. This study included neonates aged less than 28 days, diagnosed with suspected sepsis, and had no previous history of antibiotics administration. Patients underwent clinical assessment, laboratory examination, and blood culture. Patients were grouped into sepsis and non-sepsis based on the blood culture results. The median hematological examination and the range of NLR and PLR in both the sepsis and non-sepsis groups were subjected to analysis using the Mann-Whitney U test to assess differences. NLR and PLR optimal cut-off values were determined using a receiver operator curve (ROC) with a confidence interval of 95%. A total of 137 neonates were enrolled, of which 49 were classified as sepsis and 89 as non-sepsis based on blood culture results. The optimal cutoff values for NLR and PLR were 2.75 and 11.73. Using those cutoff values, NLR and PLR could predict neonatal sepsis with sensitivities of 52.1% and 47.9%, specificities of 50.6% and 47.2%, area under the curve (AUC) of 0.46 and 0.47, with p=0.525 and p=0.662, respectively. Further investigation is warranted to refine the NLR and PLR utility and enhance diagnostic accuracy in clinical practices.

Predictive biomarkers of preeclampsia severity in a low resource setting: Role of red blood cell indices, NLR, and albumin-to-creatinine ratio.

Preeclampsia (PE), a serious medical condition with substantial maternal and perinatal implications, poses a significant challenge, particularly in high-incidence countries like Indonesia. Red blood cell (RBC) indices, neutrophil-to-lymphocyte ratio (NLR), and microalbuminuria (albumin-to-creatinine ratio (ACR)) may signal systemic inflammation and endothelial dysfunction, recently recognized as potential indicators for diagnosing and predicting disease severity. The aim of this study was to analyze RBC indices, NLR, and ACR changes in women with PE and their potential for predicting disease severity. A cross-sectional study was conducted at multi-center hospitals across Medan, Indonesia, from June 2022 to June 2023. The patients were grouped into PE cases with and without severe features. Demographic characteristics and complications were recorded while blood and urine were tested. The Chi-squared test, Fisher's exact test and Mann-Whitney test were used to determine biomarkers associated with severe PE. A total of 208 PE patients were included in the study (104 patients for each PE with and without severe features). Our data indicated that PE patients with severe features had higher red cell distribution width (18.5% vs 13.7%; p<0.001), NLR (5.66% vs 4.1%; p<0.001), and ACR (755.97 mg/dL vs 468.63 mg/dL; p<0.001) compared to those without severe features. In contrast, the platelet count was lower in severe features than those without (21.9 × 106/µL vs 27.0 × 106/µL; p=0.002). This study highlighted that PE patients with severe features predominantly had higher levels of RDW, NLR, and ACR and lower platelet counts compared to those without severe features. Therefore, basic tests such as complete blood count and urinalysis, which are inexpensive and feasible in primary care settings with limited resources, offer hope as valuable diagnostic biomarkers for pregnant women diagnosed with PE in a low resource setting.

Neutrophil-to-lymphocyte ratio as a predictor of low cardiac output syndrome after open heart surgery in children with congenital heart disease.

Neutrophil-to-lymphocyte ratio (NLR) as a predictor in determining low cardiac output syndrome (LCOS) has not been widely reported. The aim of this study was to explore the role of pre-surgery, 0-, 4-, and 8-hour post-surgery NLR as predictors of LCOS incidence after open heart surgery in children with congenital heart disease (CHD). This study used a prognostic test with a prospective cohort design and was conducted from December 2020 until June 2021 at the cardiac intensive care unit (CICU) of Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The subject consisted of children aged one month to 18 years who underwent open heart surgery using a cardiopulmonary bypass (CPB) machine. A receiver operating characteristic curve was applied to identify the predictive performance of NLR for poor outcomes (LCOS incidence). Out of 90 patients included in the study, 25 (27.8%) of them developed LCOS between 3 to 53 hours post-surgery. All NLR values (pre-surgery and 0-, 4-, and 8-hours post-surgery) were associated with the incidence of LCOS. Pre-surgery NLR (cut-off value ≥0.88) had a fair predictive value (area under curve (AUC) 70; 95%CI: 57-83) for predicting LCOS incidence with sensitivity and specificity of 64% and 64.62%, respectively. NLR 0-hour post-surgery (cut-off value ≥4.73) had a good predictive value (AUC 81; 95%CI: 69-94) for predicting LCOS incidence, with 80% sensitivity and 80% specificity. NLR 4- and 8-hours post-surgery had very good predictive values (AUC 97%; 95%CI: 92-100 and 98; 95%CI: 94-100, respectively), with cut-off values ≥6.19 and ≥6.78, had the same 92% sensitivity and the same 96% sensitivity. The presence of LCOS was associated with mortality (odds ratio of 5.11 with 95%CI: 3.09-8.46). This study highlights that pre-surgery, 0-, 4-, and 8-hours post-surgery NLR can be predictors of LCOS after open heart surgery in children with CHD.

Assessment of neutrophil/lymphocyte ratio and mean platelet volume values in patients with diabetes mellitus diagnosis: A case-control study.

Diabetes mellitus, fundamentally characterized by hyperglycemia, leads to significant metabolic disturbances. Type 2 diabetes mellitus is a chronic, inflammatory, preventable metabolic disease that is a significant health issue globally. The neutrophil-to-lymphocyte ratio (NLR) is an essential marker of systemic inflammation. We aimed to reveal the relationship between long-term glucose control and NLR, mean platelet volume (MPV), and red blood cell width in patients with type 2 diabetes. This was a retrospective case-control study. A total of 3532 applications in 2 years time were identified. Age, gender, medical history, white blood cell (WBC), hemoglobin, mean corpuscular volume (MCV), MPV, red blood cell width, NLR, hematocrit, platelet, C-reactive protein, Haemoglobin A1C data of the patients were analyzed. 1790 patients were included. A significant positive correlation was found between HbA1c and age, white blood cell, hematocrit, MCV, red blood cell width, NLR, and CRP. A statistically significant negative correlation was found between HbA1c and MCV. The results showed statistically significant differences between NLR, MPV, WBC, MCV, age, and HbA1c levels. Increased HbA1c levels are usually associated with an increase in these parameters. This is important for determining the risk of complications and protecting target organs in diabetic patients. A significant decrease in MCV levels was found as HbA1c levels increased. This suggests that evaluating red blood cells in routine controls of diabetic patients may indicate glycemic control. These findings may be valuable in early diagnosis of complications.

DNA Methylation signatures underpinning blood neutrophil to lymphocyte ratio during first week of human life.

Understanding of newborn immune ontogeny in the first week of life will enable age-appropriate strategies for safeguarding vulnerable newborns against infectious diseases. Here we conducted an observational study exploring the immunological profile of infants longitudinally throughout their first week of life. Our Expanded Program on Immunization - Human Immunology Project Consortium (EPIC-HIPC) studies the epigenetic regulation of systemic immunity using small volumes of peripheral blood samples collected from West African neonates on days of life (DOL) 0, 1, 3, and 7. Genome-wide DNA methylation and single nucleotide polymorphism markers are examined alongside matched transcriptomic and flow cytometric data. Integrative analysis reveals that a core network of transcription factors mediates dynamic shifts in neutrophil-to-lymphocyte ratios (NLR), which are underpinned by cell-type specific methylation patterns in the two cell types. Genetic variants are associated with lower NLRs at birth, and healthy newborns with lower NLRs at birth are more likely to subsequently develop sepsis. These findings provide valuable insights into the early-life determinants of immune system development.

Association of neutrophil-to-lymphocyte ratio with age and 180-day mortality after emergency surgery.

BACKGROUND: To examine the relationship between neutrophil-to-lymphocyte ratio (NLR), age, and mortality rates after emergency surgery. METHODS: In this observational study, a total of 851 patients undergoing emergency surgery between January 2022 and January 2023 were retrospective examined. Using 30 and 180 days mortality data, NLR differences and receiver operating characteristic (ROC) curves were analyzed using a 65-year threshold. A multiple logistic regression model was constructed incorporating age and NLR. Finally, Kaplan-Meier curves were constructed for mortality. RESULTS: Among 851 patients, the 30 and 180 days mortality rates were 5.2% and 10.8%, respectively. Median NLR in 30 days was 5.6 (3.1 to 9.6) in survivors and 8.7 (4.6 to 13.4) in deceased patients (p < 0.0001); in 180 days, it was 5.5 (3.1 to 9.8) and 8.8 (4.8 to 14.5), respectively (p < 0.0001). In the 30- and 180-days mortality analyses, median NLRs were 5.1 (2.9 to 8.9) and 4.9 (2.9 to 8.8) in survivors and 10.6 (6.9 to 16.6) and 9.3 (5.4 to 14.9) in deceased patients aged < 65 years, respectively. The ROC AUC in patients younger than 65 years was higher for 30 days (AUC 0.75; 95% CI 0.72 to 0.87) and 180 days (AUC 0.73; 95% CI 0.64 to 0.81). Multivariate logistic regression revealed that the NLR (odds ratio, 1.03 [95% CI 1.005 to 1.053; p = 0.0133) and age (odds ratio, 1.05 [95% CI 1.034 to 1.064; p < 0.0001) significantly contributed to the model. Survival analysis revealed differences in the 180 days mortality (p = 0.0006). CONCLUSION: We observed differences in preoperative NLR between patients who survived and those who died after emergency surgery. Age impacts the use of NLR as a mortality risk factor. TRIAL REGISTRATION: NCT06549101, retrospectively registered.

Identification of SNPs and Candidate Genes Associated with Monocyte/Lymphocyte Ratio and Neutrophil/Lymphocyte Ratio in Duroc × Erhualian F2 Population.

Understanding the pig immune function is crucial for disease-resistant breeding and potentially for human health research due to shared immune system features. Immune cell ratios, like monocyte/lymphocyte ratio (MLR) and neutrophil/lymphocyte ratio (NLR), offer a more comprehensive view of immune status compared to individual cell counts. However, research on pig immune cell ratios remains limited. This study investigated MLR and NLR in a Duroc × Erhualian F2 resource population. Heritability analysis revealed high values (0.649 and 0.688 for MLR and NLR, respectively), suggesting a strong genetic component. Furthermore, we employed an ensemble-like GWAS (E-GWAS) strategy and functional annotation analysis to identify 11 MLR-associated and 6 NLR-associated candidate genes. These genes were significantly enriched in immune-related biological processes. These findings provide novel genetic markers and candidate genes associated with porcine immunity, thereby providing valuable insights for addressing biosecurity and animal welfare concerns in the pig industry.

The Relationship between Vitamin D, Inflammatory Markers, and Insulin Resistance in Children.

OBJECTIVE: In this study, we investigated 25-hydroxyvitamin D (25(OH)D, vitamin D), inflammatory hematologic ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte/HDL-C ratio (MHR) and plasma atherogenic index (PAI) and possible relationships with insulin resistance (IR) in children. METHODS: A total of 210 individuals, including 96 children with IR and 114 children without IR, aged 6-18 years, who were admitted to the Pediatric Endocrinology Outpatient Clinic at Medicine Hospital, Istanbul Atlas University were included in our study. RESULT: Compared to patients without IR, NLR, PLR, SII, and MHR were significantly higher in patients with IR. Fasting insulin, PAI, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-ß were significantly higher and quantitative insulin sensitivity check index (QUICKI) was considerably lower in patients with IR compared to those without IR. NLR, SII, and MHR were lower in normal vitamin D groups than the others (p < 0.001). PLR was lower in the group with normal vitamin D levels than the groups with insufficient or deficient levels of vitamin D (D < 21). CONCLUSIONS: We found that vitamin D deficiency in childhood is related to increased levels of circulating inflammatory markers (NLR, PLR, MHR, PAI), IR, and decreased insulin sensitivity. According to our results, supplementation of vitamin D may be beneficial in averting IR and enhanced systemic inflammation.

Predictability of Neutrophile to Lymphocyte Ratio and Platelet to Lymphocyte Ratio on the Effectiveness of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer patients: A Meta-Analysis.

OBJECTIVES: The associations between the neutrophil-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with the responses of non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICI) and the NLR/PLR predictive potential were evaluated via meta-analysis. METHODS: A systematic review was conducted using the PubMed, Embase, and The Cochrane Library databases until October 2021. The relationship between NLR/PLR and overall survival (OS) and progression-free survival (PFS) was evaluated using pooled hazard ratios (HR). The relationship between NLR/PLR and overall response rate (ORR) and disease control rate (DCR) was assessed via pooled odds ratios (OR). Heterogeneity between studies, publication bias, subgroup and sensitivity analyses, trim and fill meta-analysis, and the contour-enhanced funnel plot were performed using the R software. RESULTS: A total of 44 (out of 875) studies met the eligibility criteria, providing a sample size of 4597 patients. Patients with a high NLR were statistically significantly associated with worse outcomes, including OS (pooled HR = 2.44; P < 0.001), PFS (pooled HR = 2.06; P < 0.001), DCR (pooled OR = 0.71; P < 0.001), and ORR (pooled OR = 0.33; P < 0.001). Similarly, a high PLR was associated with poorer outcomes in response to ICI drugs, including OS (pooled HR = 2.13; P < 0.001) and PFS (pooled HR = 1.61; P < 0.001). CONCLUSION: High NLR and PLR were associated with a statistically significant reduction in the efficacy of ICI drugs in NSCLC patients. Thereby, it is possible to use NLR and PLR as potential and available biomarkers in the clinical practice to predict the outcome of ICI treatment in NSCLC patients.