BACKGROUND: Human aging and white blood cell (WBC) count are complex traits influenced by multiple genetic factors. Predictors of chronological age have been developed using epigenetic clocks. However, the bidirectional causal effects between epigenetic clocks and WBC count have not been fully examined.
METHODS: This study employed Mendelian randomization (MR) to analyze summary statistics from four epigenetic clocks involving 34,710 participants, alongside data from the Blood Cell Consortium encompassing 563,946 individuals. We primarily explored bidirectional causal relationships using the random-effects inverse-variance weighted method, supplemented by additional MR methods for comprehensive analysis. Additionally, multivariate MR was applied to investigate independent effects of WBC count on epigenetic age acceleration.
RESULTS: In the two-sample univariate MR (UVMR) analysis, we observed that a decrease in lymphocyte count markedly accelerated aging according to the PhenoAge, GrimAge, and HannumAge metrics (all P < 0.01, β < 0), though it did not affect Intrinsic Epigenetic Age Acceleration (IEAA). Conversely, an increase in neutrophil count significantly elevated PhenoAge levels (β: 0.38; 95% CI 0.14, 0.61; P = 1.65E-03 < 0.01). Reverse MR revealed no significant causal impacts of epigenetic clocks on overall WBC counts. Furthermore, in multivariate MR, the impact of lymphocyte counts on epigenetic aging metrics remained statistically significant. We also identified a marked causal association between neutrophil counts and PhenoAge, GrimAge, and HannumAge, with respective results showing strong associations (PhenoAge β: 0.78; 95% CI 0.47, 1.09; P = 8.26E-07; GrimAge β: 0.55; 95% CI 0.31, 0.79; P = 5.50E-06; HannumAge β: 0.42; 95% CI 0.18, 0.67; P = 6.30E-04). Likewise, eosinophil cell count demonstrated significant association with HannumAge (β: 0.33; 95% CI 0.13, 0.53; P = 1.43E-03 < 0.01).
CONCLUSIONS: These findings demonstrated that within WBCs, lymphocyte and neutrophil counts exert irreversible and independent causal effects on the acceleration of PhenoAge, GrimAge, and HannumAge. Our findings highlight the critical role of WBCs in influencing epigenetic clocks and underscore the importance of considering immune parameters when interpreting epigenetic age.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and metals were associated with decreased lung function, but co-exposure effects and underlying mechanism remained unknown.
METHODS: Among 1,123 adults from National Health and Nutrition Examination Survey 2011-2012, 10 urinary PAHs, 11 urinary metals, and peripheral white blood cell (WBC) count were determined, and 5 lung function indices were measured. Least absolute shrinkage and selection operator, Bayesian kernel machine regression, and quantile-based g-computation were used to estimate co-exposure effects on lung function. Mediation analysis was used to explore mediating role of WBC.
RESULTS: These models demonstrated that PAHs and metals were significantly associated with lung function impairment. Bayesian kernel machine regression models showed that comparing to all chemicals fixed at median level, forced expiratory volume in 1 s (FEV1)/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25 and 75% decreased by 1.31% (95% CI: 0.72%, 1.91%), 231.62 (43.45, 419.78) mL/s, and 131.64 (37.54, 225.74) mL/s respectively, when all chemicals were at 75th percentile. In the quantile-based g-computation, each quartile increase in mixture was associated with 104.35 (95% CI: 40.67, 168.02) mL, 1.16% (2.11%, 22.40%), 294.90 (78.37, 511.43) mL/s, 168.44 (41.66, 295.22) mL/s decrease in the FEV1, FEV1/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25% and 75%, respectively. 2-Hydroxyphenanthrene, 3-Hydroxyfluorene, and cadmium were leading contributors to the above associations. WBC mediated 8.22%-23.90% of association between PAHs and lung function.
CONCLUSIONS: Co-exposure of PAHs and metals impairs lung function, and WBC could partially mediate this relationship. Our findings elucidate co-exposure effects of environmental mixtures on respiratory health and underlying mechanisms, suggesting that focusing on highly prioritized toxicants would effectively attenuate adverse effects.

UNASSIGNED: White blood cell (WBC) counts has been identified as a prognostic biomarker which frequently predict adverse outcomes and mortality risk in various conditions. However, evidence for the association between WBC counts and short-term outcomes after intracranial tumor resection remains limited. This study aimed to explore associations between preoperative WBC counts and thirty-day surgical mortality after craniotomy in adult intracranial tumor patients.
UNASSIGNED: This retrospective cohort study performed secondary analysis of 18,049 intracranial tumor craniotomy patients from the ACS NSQIP database (2012-2015). The major exposure and outcome were preoperative WBC counts and thirty-day surgical mortality, respectively. Cox regression modeling assessed the linear association between them. Non-linear associations between them were evaluated by conducting smooth curve fitting using an additive Cox proportional hazard model in conjunction with segmented linear regression modeling. Subgroup analysis and interaction testing assessed effect modification. Sensitivity analysis evaluated result robustness.
UNASSIGNED: The total thirty-day surgical mortality after craniotomy was 2.49% (450/18,049). The mean of preoperative WBC counts was 9.501 ± 4.402 × 10^9/L. Fully adjusted model shows that elevated preoperative WBC counts was independently associated with increased thirty-day surgical mortality (HR = 1.057, 95%CI: 1.040, 1.076). Further analysis revealed a non-linear association between them: below a WBC threshold of 13.6 × 10^9/L, higher WBC counts elevated thirty-day mortality (HR = 1.117; 95%CI: 1.077, 1.158), while risk plateaued and no significant mortality rise occurred above this level (HR = 1.015, 95%CI: 0.982, 1.050). Steroid usage status has a significant effect modification on the WBC-mortality association (P for interaction = 0.002). The non-linear WBC-mortality association was only present for non-steroid users (HR = 1.158, 95%CI: 1.108, 1.210) but not steroid users (HR = 1.009, 95%CI: 0.966, 1.055). The sensitivity analysis confirmed the result robustness.
UNASSIGNED: Elevated preoperative WBC counts were independently and non-linearly associated with an increased risk of thirty-day surgical mortality in adult non-steroid use patients undergoing craniotomy for intracranial tumors. As a convenient predictor, preoperative WBC data allows improved risk profiling and personalized management in adult intracranial tumor patients.

OBJECTIVE: Inflammation is thought to be a vital element in the etiology of cancer-related fatigue (CRF), and circulating blood cell parameters could be important markers of inflammatory response. However, the associations of several major blood cell counts and their derived inflammatory indices with CRF are not well described. The present study aimed to establish whether a relationship exists between the counts of three white blood cell (WBC) types, platelets, and CRF and investigate whether several systemic inflammatory indices were associated with CRF in patients with breast cancer (BC).
METHODS: A cross-sectional survey was conducted with a sample of 824 patients with BC undergoing chemotherapy. The cancer fatigue scale was administered to assess CRF. Hematological indicators, including neutrophils, lymphocytes, monocytes, and platelets, were retrieved from routine blood test. Network analyses were used to examine the associations among them.
RESULTS: Among 824 participants, the mean score of CRF was (27 ± 10), ranging from 0 to 57. The results of network models indicated that physical fatigue was negatively linked to lymphocyte counts (weight =  - 0.161), and affective fatigue was positively associated with neutrophil counts (weight = 0.070). Additionally, physical fatigue was positively linked to the platelet-to-lymphocyte ratio (PLR) (weight = 0.049).
CONCLUSIONS: There were preliminary associations of counts of three WBC types, platelet counts, and systemic inflammatory indices, with distinct dimensions of CRF in patients with BC. Findings provide empirical support for the cellular basis of fatigue-associated inflammatory states.

UNASSIGNED: Inflammation is integral to diabetes pathogenesis. The novel hematological inflammatory biomarker, platelet to white blood cell ratio (PWR), is linked with various conditions such as chronic kidney disease and stroke. However, the association of this novel clinical indicator with diabetes still remains unclear, which is investigated in this study.
UNASSIGNED: A total of 10,973 Chinese participants were included and grouped according to the tertiles of PWR (T1, T2, and T3 groups). Diagnosis of prediabetes and diabetes adhered to American Diabetes Association criteria. Binary logistic regression was adopted to assess the relationship between PWR and both diabetes and prediabetes. The dose-response relationship of PWR and diabetes was examined using restricted cubic spline regression. Subgroup and interaction analyses were conducted to investigate potential covariate interactions.
UNASSIGNED: Individuals with higher PWR had better lifestyles and lipid profiles (all P < 0.05). After adjusting for all the covariates, the T2 group had a 0.83-fold (95% CI: 0.73-0.93, P < 0.01) risk of diabetes and that for the T3 group was 0.68-fold (95% CI: 0.60-0.78. P < 0.001). Dose-response analysis identified non-linear PWR-diabetes associations in the general population and females (both P < 0.05), but absent in males. Participants with prediabetes in the T2 and T3 groups had lower risks of diabetes (OR = 0.80 for the T2 group, P < 0.001 and 0.68 for the T3 group, P < 0.001) in the full models. All the sensitivity analysis support consistent conclusions.
UNASSIGNED: An increase in PWR significantly correlates with reduced diabetes risks. A non-linear PWR-diabetes relationship exists in the general population and females, but not in males. The correlation between PWR and diabetes indicates that PWR holds potentials in early identification and prevention of diabetes.

UNASSIGNED: In recent years, diseases caused by abnormal immune-inflammatory responses have become increasingly severe. Dietary intervention involving omega-3 polyunsaturated fatty acids (ω-3 PUFAs) has emerged as a potential treatment. However, research investigating the relationship between ω-3, ω-6 PUFAs, and ω-6 to ω-3 ratio with inflammatory biomarkers remains controversial.
UNASSIGNED: To investigate the correlation between the intake of ω-3 and ω-6 PUFAs and the ratio of ω-6: ω-3 with biomarkers of inflammation, the National Health and Nutrition Examination Survey (NHANES) data (1999 to 2020) was utilized. The systemic immune-inflammation index (SII), platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and white blood cell (WBC) were selected as study subjects. Dietary data for ω-3 and ω-6 PUFAs were collected via two 24-h dietary recall interviews. SII index and other indicators were obtained from the blood routine data. The multiple linear regression and restricted cubic spline models were utilized to evaluate the association of ω-3, ω-6 PUFAs intake, and ω-6: ω-3 ratio to SII and secondary measures.
UNASSIGNED: This study involved a total of 43,155 American adults. ω-3 and ω-6 PUFAs exhibited negative correlations with SII, PLR, NLR, and WBC. The correlation between ω-6: ω-3 ratio and SII, PLR, NLR, and WBC was not significant. Furthermore, the dose-response relationship showed that the relationship between the intake of ω-3 and ω-6 PUFAs and SII was an \"L\" pattern.
UNASSIGNED: Intake of dietary ω-3 and ω-6 PUFAs reduces the levels of several inflammatory biomarkers in the body and exerts immunomodulatory effects.

Acute compartment syndrome (ACS) is a severe orthopedic issue that, if left untreated, can result in lasting nerve and muscle damage or even necessitate amputation. The association between admission laboratory blood test indicators and the occurrence of ACS in patients with tibial diaphysis fractures is currently a subject of debate. The objective of this research was to identify the contributing factors for ACS in individuals suffering from tibial diaphysis fractures. In this retrospective study, we collected data on a total of 705 individuals from our hospital, comprising 86 ACS patients and 619 non-ACS patients with tibial diaphysis fractures. These participants were categorized into two distinct groups: the ACS group and the non-ACS group. Despite the inherent limitations associated with retrospective analyses, such as potential biases in data collection and interpretation, we conducted a comprehensive analysis of demographics, comorbidities, and admission lab results. Our analytical approach included univariate analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis techniques, aiming to mitigate these limitations and provide robust findings. The statistical analysis revealed several predictors of ACS, including gender (p = 0.011, OR = 3.200), crush injuries (p = 0.004, OR = 4.622), lactic dehydrogenase (LDH) levels (p < 0.001, OR = 1.003), and white blood cell (WBC) count (p < 0.001, OR = 1.246). Interestingly, the study also found that certain factors, such as falls on the same level (p = 0.007, OR = 0.334) and cholinesterase (CHE) levels (p < 0.001, OR = 0.721), seem to provide a degree of protection against ACS. In order to better predict ACS, the ROC curve analysis was employed, which determined threshold values for LDH and WBC. The established cut-off points were set at 266.26 U/L for LDH and 11.7 × 109 cells per liter for WBC, respectively. Our research has successfully pinpointed gender, crush injuries, LDH levels, and white blood cell (WBC) count as crucial risk factors for the development of ACS in patients experiencing tibial diaphysis fractures. Furthermore, by establishing the cut-off values for LDH and WBC, we have facilitated a more personalized assessment of ACS risk, enabling clinical doctors to implement targeted early interventions and optimize patient outcomes.

UNASSIGNED: Acute kidney injury (AKI) is a common complication of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and inflammation is the potential link between AKI and AECOPD. However, little is known about the incidence and risk stratification of AKI in critically ill AECOPD patients. In this study, we aimed to establish risk model based on white blood cell (WBC)-related indicators to predict AKI in critically ill AECOPD patients.
UNASSIGNED: For the training cohort, data were taken from the Medical Information Mart for eICU Collaborative Research Database (eICU-CRD) database, and for the validation cohort, data were taken from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. The study employed logistic regression analysis to identify the major predictors of WBC-related biomarkers on AKI prediction. Subsequently, a risk model was developed by multivariate logistic regression, utilizing the identified significant indicators.
UNASSIGNED: Finally, 3551 patients were enrolled in training cohort, 926 patients were enrolled in validation cohort. AKI occurred in 1206 (33.4%) patients in training cohort and 521 (56.3%) patients in validation cohort. According to the multivariate logistic regression analysis, four WBC-related indicators were finally included in the novel risk model, and the risk model had a relatively good accuracy for AKI in the training set (C-index, 0.764, 95% CI 0.749-0.780) as well as in the validation set (C-index, 0.738, 95% CI: 0.706-0.770). Even after accounting for other models, the critically ill AECOPD patients in the high-risk group (risk score > 3.44) still showed an increased risk of AKI (odds ratio: 4.74, 95% CI: 4.07-5.54) compared to those in low-risk group (risk score ≤ 3.44). Moreover, the risk model showed outstanding calibration capability as well as therapeutic usefulness in both groups for AKI and ICU mortality and in-hospital mortality of critical ill AECOPD patients.
UNASSIGNED: The novel risk model showed good AKI prediction performance. This risk model has certain reference value for the risk stratification of AECOPD complicated with AKI in clinically.

UNASSIGNED: Inflammation participates in the pathology and progression of secondary brain injury after intracerebral hemorrhage (ICH). This meta-analysis intended to explore the prognostic role of inflammatory indexes, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), white blood cell (WBC), and C-reactive protein (CRP) in ICH patients.
UNASSIGNED: Embase, PubMed, Web of Science, and Cochrane Library were searched until June 2023. Two outcomes, including poor outcome and mortality were extracted and measured. Odds ratio (OR) and 95% confidence interval (CI) were presented for outcome assessment.
UNASSIGNED: Forty-six studies with 25,928 patients were included in this meta-analysis. The high level of NLR [OR (95% CI): 1.20 (1.13-1.27), p < 0.001], WBC [OR (95% CI): 1.11 (1.02-1.21), p = 0.013], and CRP [OR (95% CI): 1.29 (1.08-1.54), p = 0.005] were related to poor outcome in ICH patients. Additionally, the high level of NLR [OR (95% CI): 1.06 (1.02-1.10), p = 0.001], WBC [OR (95% CI): 1.39 (1.16-1.66), p < 0.001], and CRP [OR (95% CI): 1.02 (1.01-1.04), p = 0.009] were correlated with increased mortality in ICH patients. Nevertheless, PLR was not associated with poor outcome [OR (95% CI): 1.00 (0.99-1.01), p = 0.749] or mortality [OR (95% CI): 1.00 (0.99-1.01), p = 0.750] in ICH patients. The total score of risk of bias assessed by Newcastle-Ottawa Scale criteria ranged from 7-9, which indicated the low risk of bias in the included studies. Publication bias was low, and stability assessed by sensitivity analysis was good.
UNASSIGNED: This meta-analysis summarizes that the high level of NLR, WBC, and CRP estimates poor outcome and higher mortality in ICH patients.

BACKGROUND: White blood cell (WBC) count increases during pregnancy, necessitating reliable reference intervals for assessing infections and pregnancy-related complications. This study aimed to establish comprehensive reference intervals for WBC counts during pregnancy.
METHODS: The analysis included 17,737 pregnant women, with weekly WBC count measurements from pre-pregnancy to postpartum. A threshold linear regression model determined reference intervals, while Harris and Boyd\'s test partitioned the intervals.
RESULTS: WBC count exhibited a significant increase during pregnancy, characterized by a rapid rise before 7 weeks of gestation, followed by a plateau. Neutrophils primarily drove this increase, showing a similar pattern. The threshold regression model and Harris and Boyd\'s test supported partitioned reference intervals for WBC counts: 4.0-10.0 × 10^9/L for < = 2 weeks, 4.7-11.9 × 10^9/L for 3-5 weeks, and 5.7-14.4 × 10^9/L for > = 6 weeks of gestation. These reference intervals identified pregnant women with high WBC counts, who had a higher incidence of pregnancy-related complications including placenta previa, oligohydramnios, secondary uterine inertia, and intrauterine growth restriction.
CONCLUSIONS: This study establishes comprehensive reference intervals for WBC counts during pregnancy. Monitoring WBC counts is clinically relevant, as elevated levels are associated with an increased risk of infection and pregnancy-related complications.