Search

Background/aim: Inflammation-based prognostic scores have shown prognostic significance and have been associated with clinical outcomes in various types of cancer. Inflammation is known to promote tumor progression leading to reduced survival. In pancreatic cancer, systemic inflammation is common and contributes to its dismal prognosis. Although the prognosis of pancreatic cancer is improving with the introduction of new drugs, the prognostic indicators are still poorly understood. The present study aimed to evaluate inflammation-based prognostic scores in patients with metastatic pancreatic cancer receiving first-line chemotherapy., Patients and Methods: A total of 43 patients with metastatic pancreatic cancer undergoing first-line chemotherapy (gemcitabine+nab-paclitaxel and mFOLFIRINOX) in our institution were analyzed. Baseline clinicopathological and pre-treatment laboratory data were collected. Survival was estimated using the Kaplan-Meier method and survival differences were evaluated using the log-rank test., Results: In the whole cohort, we identified lymphocyte-to-monocyte ratio ≥3, systemic inflammatory response index <2.3, carcinoembryonic antigen <2.5, neutrophil-to-lymphocyte ratio <5, Memorial Sloane Kettering score <2, and prognostic index <2 as prognostic markers associated with improved overall survival in patients receiving first-line chemotherapy., Conclusion: The current analysis showed an association between inflammatory-based prognostic markers and overall survival in patients with metastatic pancreatic cancer treated in a real-world setting at a single institution., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The systemic immune-inflammation index (SII) is a calculated biomarker developed to predict the prognosis of malignant tumors. This study evaluated the influence of the SII in patients with esophageal cancer (EC) who underwent curative resection., Patients and Methods: Patients who underwent radical esophagectomy and lymph node dissection for EC were enrolled. The SII was calculated as follows: neutrophil count (cell/mm 3 ) × platelet count (cell/mm 3 ×10 3 )/lymphocyte count (cell/mm 3 ). The SII, patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were assessed., Results: A total of 180 patients were included in this study. The cutoff value of the SII was set at 500 according to previous studies. Of the 180 patients, 100 were classified into the SII-high group and 80 into the SII-low group. The 3- and 5-year OS rates were 59.0% and 54.0%, respectively, in the SII-high group and 80.0% and 75.0%, respectively, in the SII-low group, showing significant differences between the groups (p=0.001). A multivariate analysis for the OS demonstrated that the SII was an independent prognostic factor (hazard ratio=2.333, 95% confidence interval=1.411-3.860, p<0.001), with similar results obtained for the RFS. Furthermore, hematological recurrence was significantly higher in the SII-high group than in the SII-low group (36.0% vs. 17.5%, p=0.006)., Conclusion: The preoperative SII was an independent prognostic factor for OS and RFS in patients with EC who underwent curative resection. Thus, the SII can be a useful marker for the treatment and management of EC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype, posing numerous challenges in clinical decision-making. Biomarkers are essential to personalize management of TNBC patients. While tumor infiltrating lymphocytes (TILs) are validated prognostic biomarkers, the requirement for tumor biopsy limits their routine use. Therefore, more accessible and reliable quantitative biomarkers are needed. Given the significant role of systemic inflammatory response in tumor onset and progression, assessing inflammatory cells via liquid biopsies emerges as a promising alternative., Patients and Methods: The PERCEPTION study, conducted at Centre Jean Perrin in France, aims to determine the correlation between TILs and peripheral blood components at diagnosis. An interim analysis was conducted after enrolling 50% of the estimated population, to evaluate study feasibility and preliminary correlations between blood cell counts and TILs., Results: Sixty-one patients were enrolled over 4.5 years, demonstrating a good inclusion rate with minimal missing data. Preliminary results for 36 analyzable patients showed no correlation between the neutrophil-to-lymphocyte ratio (NLR) and TILs (r s =-0.19, 95%CI=-0.49-0.16, p=0.3). However, a moderate, positive, statistically significant correlation was found between NLR and the CD8/FoxP3 TILs ratio (r s =0.36, 95%CI=0.03-0.64, p=0.043). The probabilistic index of 0.7 (p=0.06) between NLR-high and NLR-low groups for this ratio supports the correlation., Conclusion: The interim analysis of the PERCEPTION study confirms the feasibility of correlating blood cell counts with TILs in TNBC. Although no significant correlation was observed between NLR and TILs, the moderate positive correlation between the CD8/FoxP3 ratio and TILs suggests a potential link between systemic inflammation and local immune response. These findings underscore the potential of blood-based markers as non-invasive surrogates for TILs, encouraging further research to enhance prognosis and guide treatment strategies in TNBC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: We hypothesized that the inflammatory burden index (IBI) is a promising biomarker for esophageal cancer (EC) treatment and management. To confirm our hypothesis, we evaluated the prognostic impact of IBI in patients with EC who received curative treatment., Patients and Methods: We conducted a retrospective review of medical records and collected data from consecutive patients with EC who underwent curative resection at Yokohama City University between 2005 and 2020. The IBI score was calculated as the C-reactive protein level multiplied by the neutrophil-to-lymphocyte ratio., Results: In total, 180 patients with EC were included in this study. The 3- and 5-year overall survival (OS) rates were 72.9% and 63.4%, respectively, in the IBI-low group, and 38.2% and 32.5% in the IBI-high group (p<0.001). In the multivariate analysis, IBI was identified as a significant prognostic factor for OS [hazard ratio (HR)=2.372; 95% confidence interval CI=1.478-3.806, p<0.001]. In addition, the 3- and 5-year recurrence-free survival (RFS) rates were 52.9% and 47.8%, respectively, in the IBI-low group, and 22.9% and 17.2% in the IBI-high group (p<0.001). In the multivariate analysis, IBI was identified as a significant prognostic factor for RFS (HR=2.484; 95%CI=1.373-4.494, p<0.001). When comparing the recurrence patterns between the IBI-high and IBI-low groups, there were significant differences in lymph node recurrence (46.0% vs. 26.2%, p=0.010) and hematological recurrence (52.0% vs. 18.5%, p<0.001)., Conclusion: IBI affects both the short- and long-term oncological outcomes. Thus, IBI may be a promising prognostic factor for the treatment and management of EC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To investigate the association of clinical findings and indocyanine green angiography (ICGA) score with inflammatory markers derived from complete blood count (CBC) parameters in patients with Vogt-Koyanagi-Harada (VKH) to determine the diagnostic and predictive role., Methods: Demographic characteristics, presenting complaints, ocular findings, optical coherence tomography findings, ICGA scores and best corrected visual acuity were recorded in treatment-naive VKH patients at presentation. Patients were divided into two groups as acute stage and chronic recurrent stage. CBC parameters were noted in patients at presentation and healthy controls (HC, n  = 25). Neutrophil-lymphocyte-platelet-monocyte counts, neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), monocyte/lymphocyte and systemic immune-inflammation index (SII) were recorded. The association between these markers and clinical severity were evaluated., Results: Thirty-two patients with VKH (23 females/9 males) with a mean age of 34.1 ± 14.6 years were included in the study. There was an increase in neutrophil count, NLR and SII in patients with VKH compared to HC ( p  < 0.001). The cut-off values for these three parameters were 4.37, 2.24 and 562.35, respectively. Twenty-six patients presented in the acute stage and six patients presented in the chronic recurrent stage. Choroidal thickness, early stromal hyperfluorescence and total ICGA scores were higher in patients presenting in the acute stage ( p  < 0.001, 0.001 and 0.025, respectively). Patients with higher disease severity at presentation were treated earlier. Early stromal vessel hyperfluorescence and choroidal vasculitis scores were correlated with decreased lymphocyte count, increased NLR, PLR and SII ( p  < 0.05)., Conclusion: CBC-derived inflammatory parameters indicate that VKH is a systemic inflammation. These parameters can be used in the diagnosis and determination of disease severity of VKH.

Background: Pericardial fluid (PF) contains cells, proteins, and inflammatory mediators, such as cytokines, chemokines, growth factors, and matrix metalloproteinases. To date, we lack an adequate understanding of the inflammatory response that acute injury elicits in the pericardial space., Objective: To characterize the inflammatory profile in the pericardial space acutely after ischemia/reperfusion., Methods: Pigs were used to establish a percutaneous ischemia/reperfusion injury model. PF was removed from pigs at different time points postanesthesia or postischemia/reperfusion. Flow cytometry was used to characterize the immune cell composition of PF, while multiplex analysis was performed on the acellular portion of PF to determine the concentration of inflammatory mediators. There was a minimum of 3 pigs per group., Results: While native PF mainly comprises macrophages, we show that neutrophils are the predominant inflammatory cell type in the pericardial space after injury. The combination of acute ischemia/reperfusion (IR) and repeatedly accessing the pericardial space significantly increases the concentration of interleukin-1 beta (IL-1β) and interleukin-1 receptor antagonist (IL-1ra). IR significantly increases the pericardial concentration of TGFβ1 but not TGFβ2. We observed that repeated manipulation of the pericardial space can also drive a robust pro-inflammatory response, resulting in a significant increase in immune cells and the accumulation of potent inflammatory mediators in the pericardial space., Conclusion: In the present study, we show that both IR and surgical manipulation can drive robust inflammatory processes in the pericardial space, consisting of an increase in inflammatory cytokines and alteration in the number and composition of immune cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Systemic sclerosis (SSc) is a challenging autoimmune disease characterized by progressive fibrosis affecting the skin and internal organs. Despite the known infiltration of macrophages and neutrophils, their precise contributions to SSc pathogenesis remain elusive. In this study, we elucidated that CD206 hi MHCII lo M2-like macrophages constitute the predominant pathogenic immune cell population in the fibrotic skin of a bleomycin-induced SSc mouse model. These cells emerged as pivotal contributors to the profibrotic response by orchestrating the production of TGF-β1 through a MerTK signaling-dependent manner. Notably, we observed that neutrophil infiltration was a prerequisite for accumulation of M2-like macrophages. Strategies such as neutrophil depletion or inhibition of CXCR1/2 were proven effective in reducing M2-like macrophages, subsequently mitigating SSc progression. Detailed investigations revealed that in fibrotic skin, neutrophil-released neutrophil extracellular traps were responsible for the differentiation of M2-like macrophages. Our findings illuminate the significant involvement of the neutrophil-macrophage-fibrosis axis in SSc pathogenesis, offering critical information for the development of potential therapeutic strategies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gut affecting both adults and children. Neutrophil extracellular traps (NETs) are structures released by activated neutrophils, potentially contributing to tissue damage in various diseases. This study aimed to explore the presence and role of NETs in pediatric IBD. We compared intestinal biopsies and peripheral blood from 20 pediatric IBD patients (UC and CD) to controls. Biopsy staining and techniques for neutrophil activation were used to assess neutrophil infiltration and NET formation. We also measured the enzymatic activity of key NET proteins and evaluated NET formation in UC patients in remission. Both UC and CD biopsies showed significantly higher levels of neutrophils and NETs compared to controls ( p < 0.01), with UC exhibiting the strongest association. Peripheral blood neutrophils from UC patients at diagnosis displayed increased NET formation compared to controls and CD patients. Interestingly, NET formation normalized in UC patients following remission-inducing treatment. This pilot study suggests a potential role for NETs in pediatric IBD, particularly UC. These findings warrant further investigation into the mechanisms of NET involvement and the potential for targeting NET formation as a therapeutic strategy.

Epidural fibrosis is a primary contributor to the failure of laminectomy surgeries, leading to the development of failed back surgery syndrome (FBSS). Post-laminectomy, neutrophils infiltrate the surgical site, generating neutrophil extracellular traps (NETs) that contribute to epidural fibrosis. Reactive oxygen species (ROS) play a pivotal role in mediating NETs formation. Molecular hydrogen, recognized for its selective antioxidant properties and biosafety, emerges as a potential therapeutic gas in suppressing epidural fibrosis. In this study, we developed an in-situ hydrogen release hydrogel that inhibits the formation of NETs and mitigates epidural scarring. Biodegradable magnesium (Mg) microspheres served as a hydrogen source, coated with PLGA to regulate hydrogen release. These microspheres (Mg@PLGA) were then incorporated into a PLGA-PEG-PLGA thermosensitive hydrogel (Mg@PLGA@Gel), providing a surgical implant for sustained, long-term hydrogen release. In vitro experiments confirmed the biocompatibility of the system, demonstrating that hydrogen produced by Mg@PLGA effectively neutralizes neutrophil intracellular ROS and inhibits NETs formation. Histological analyses, including H&E staining, MRI, Masson staining, and immunohistochemistry, collectively indicate that Mg@PLGA@Gel is biocompatible and effectively inhibits epidural fibrosis post-laminectomy. Furthermore, Mg@PLGA@Gel inhibits ROS accumulation and NETs formation at the surgical site. These findings suggest that Mg@PLGA@Gel ensures continuous, therapeutic hydrogen concentration, providing relief from epidural fibrosis in a laminectomy mouse model. STATEMENT OF SIGNIFICANCE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Blue-green neutrophilic inclusions (BGNI), also known as "death bodies," are bright green structures observed in the cytoplasm of neutrophils or monocytes and are closely associated with acute liver failure, lactic acidosis, and other serious diseases. Some studies suggested a potential association with phagocytic lipofuscin released by damaged liver cells. The presence of BGNI typically indicated a poor prognosis. We presented two cases. Case 1 was diagnosed with novel bunyavirus infection and exhibited severe hepatic impairment and coagulation dysfunction along with the presence of BGNI in neutrophils. Despite receiving comprehensive symptomatic treatment, the patient's condition rapidly deteriorated leading to eventual demise. Case 2 had severe liver injury caused by wasp stings, and BGNI was observed. Following active treatment measures, the patient eventually achieved recovery. Throughout the disease course of case 1, there was a progressive deepening in color and increase in quantity of BGNI. Conversely, case 2 demonstrated an opposite trend. Based on the comparison of clinical outcomes and variations in color and quantity of BGNI between these two patients, it was found that an increase in the number and deepening of BGNI color corresponded to worsening condition. Conversely, a decrease in quantity and lightening of color indicated improvement. Hence, these findings suggest a possible association between changes in BGNI characteristics and prognosis., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Background: Immunoglobulin derived AL amyloidosis and transthyretin derived ATTR amyloidosis are the most common forms of cardiac amyloidosis. Both may present with cardiac arrhythmias, heart failure, and extracardiac symptoms. Disease outcome is often fatal. Recently, it was proposed that amyloid may cause cardiac inflammation. Here we tested the hypothesis that immune cell infiltration in cardiac tissue correlates with clinicopathological patient characteristics., Patients and Methods: Myocardial biopsies from 157 patients with cardiac amyloidosis (46.5% AL, 53.3% ATTR) were immunohistochemically assessed for the presence and amount of T lymphocytes (CD3), macrophages (CD68) and neutrophils (MPO). Amyloid load, cardiomyocyte diameter, apoptosis (Caspase 3), necrosis (complement 9), and various clinical parameters were assessed and correlated with immune cell density., Results: Myocardial tissue was infiltrated with T lymphocytes (CD3), macrophages (CD68) and neutrophils (MPO) with variable amounts. Significant correlations were found between the number of macrophages and NYHA class. No correlations were found between the presence and amount of T lymphocytes, neutrophils and clinicopathological patient characteristics., Conclusion: The significant correlation between cardiac macrophage density and heart failure points towards a significant role of macrophages in disease pathology., (© 2024. The Author(s).)

Objectives: To determine the correlation between inflammatory indices and the Tumour-Node-Metastasis stage of oesophageal carcinoma., Methods: The prospective study was conducted from January 2021 to January 2023 at the Department of Upper Gastrointestinal Surgery, Dr Ruth K.M. Pfau Civil Hospital, Karachi, and comprised patients of either gender aged 18- 60 years with biopsy-proven oesophageal cancer. Blood samples were drawn and on the basis of plasma obtained, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, C-reactive protein-to-albumin ratio, lymphocyte-tomonocyte ratio and platelet-to red cell distribution width ratio were calculated. Modified Glasgow Prognostic Score was calculated on the basis of C-reactive protein and albumin levels. Values were compared with tumour length, depth of invasion, lymph node status, vascular involvement, metastasis, pathological subtype and grade of differentiation. Data was analysed using SPSS 24., Results: Of the 220 patients aged 46.1±14.2 years, 120(54%) were females and 100(46%) were males. C-reactive protein-to-albumin ratio demonstrated the highest predictive power for advanced disease stage (p=0.003). Elevated neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (p=0.010 and p=0.044) were positively correlated with node stage, while elevated platelet-to-lymphocyte ratio was associated with advanced clinical stage (p=0.046). C-reactive protein-to-albumin ratio exhibited positive association with higher tumour stage (p=0.033), node stage (p<0.001) and clinical stage IV (p<0.001). Modified Glasgow Prognostic Score was significantly associated with advanced clinical stage (p<0.001)., Conclusion: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, C-reactive protein-to-albumin ratio, and Modified Glasgow Prognostic Score could be used effectively as a predictor of advanced oesophageal cancer.

Systemic immune responses caused by chronic hypercholesterolaemia contribute to atherosclerosis initiation, progression and complications 1 . However, individuals often change their dietary habits over time 2 , and the effects of an alternating high-fat diet (HFD) on atherosclerosis remain unclear. Here, to address this relevant issue, we developed a protocol using atherosclerosis-prone mice to compare an alternating versus continuous HFD while maintaining similar overall exposure periods. We found that an alternating HFD accelerated atherosclerosis in Ldlr -/- and Apoe -/- mice compared with a continuous HFD. This pro-atherogenic effect of the alternating HFD was also observed in Apoe -/- Rag2 -/- mice lacking T, B and natural killer T cells, ruling out the role of the adaptive immune system in the observed phenotype. Discontinuing the HFD in the alternating HFD group downregulated RUNX1 3 , promoting inflammatory signalling in bone marrow myeloid progenitors. After re-exposure to an HFD, these cells produced IL-1β, leading to emergency myelopoiesis and increased neutrophil levels in blood. Neutrophils infiltrated plaques and released neutrophil extracellular traps, exacerbating atherosclerosis. Specific depletion of neutrophils or inhibition of IL-1β pathways abolished emergency myelopoiesis and reversed the pro-atherogenic effects of the alternating HFD. This study highlights the role of IL-1β-dependent neutrophil progenitor reprogramming in accelerated atherosclerosis induced by alternating HFD., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Acute liver failure (ALF) is an acute liver disease with a high mortality rate in clinical practice, characterized histologically by extensive hepatocellular necrosis and massive neutrophil infiltration. However, the role of these abnormally infiltrating neutrophils during ALF development is unclear. Here, in an ALF mouse model, metabolites were identified that promote the formation of neutrophil extracellular traps (NETs) in the liver, subsequently influencing macrophage differentiation and disease progression. ALF occurs with abnormalities in hepatic and intestinal metabolites. Abnormal metabolites (LTD4 and glutathione) can directly, or indirectly via reactive oxygen species, promote NET formation of infiltrating neutrophils, which subsequently regulate macrophages in a pro-inflammatory M1-like state, inducing an amplification of the destructive effects of inflammation. Together, this study provides new insights into the role of NETs in the pathogenesis of ALF., (© 2024 Federation of European Biochemical Societies.)

Background: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery., Patients and Methods: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model., Results: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%., Conclusions: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment., (© 2024. Society of Surgical Oncology.)

Bullous pemphigoid (BP) is a subepidermal blistering skin disease with a complex pathogenesis involving various immune cells. However, the transcriptional features of these cells remain poorly defined. In this study, we constructed a comprehensive and single-cell resolution atlas of various immune cells within BP skin lesions through integrative single-cell analysis, flow cytometry, and multiplex immunohistochemistry. We observed prominent expansion and transcriptional changes in mast cells, macrophages, basophils, and neutrophils within BP lesions. Mast cells within the lesions adopted an active state and exhibited an elevated capacity for producing proinflammatory mediators. We observed an imbalance of macrophages/dendritic cells within BP lesions. Two macrophage subpopulations (NLRP3 + and C1q + ) with distinct transcriptional profiles were identified and upregulated effector programs. T-peripheral helper-like T helper 2 cells were expanded in skin lesions and peripheral blood of patients with BP and were capable of promoting B-cell responses. In addition, we observed clonally expanded granzyme B-positive CD8 + T cells within BP lesions. Chemokine receptor mapping revealed the potential roles of macrophages and mast cells in recruiting pathogenic immune cells and underlying mechanisms within BP lesions. Thus, this study reveals key immune pathogenic features of BP lesions, thereby providing valuable insights for potential therapeutic interventions in this disease., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The biological role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Apex1) in modulating systemic inflammation remains unclear. This study aimed to assess the impact of Apex1 deficiency on systemic inflammation triggered by lipopolysaccharide (LPS) in a murine model. The methods involved transcriptomic analysis and assessments of inflammatory responses in age-matched 8-week-old Apex1 +/- and wild-type Apex1 +/+ mice, generated using the CRISPR/Cas9 system. Apex1 +/- mice displayed no overt changes in body weight, however, Apex1 protein expressions in tissues were significantly reduced compared to wild-type mice. Furthermore, in Apex1 +/- mice transcriptomic analysis showed that genes associated with antioxidant pathways were downregulated, and levels of superoxide production, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malondialdehyde (MDA) were increased. Moreover, hematological analysis showed increased neutrophil levels and a twofold increase in the count of splenic lymphocyte antigen 6 family member G + (Ly6G + ) neutrophils in the Apex1 +/- mice compared to those in Apex1 +/+ mice. Furthermore, following LPS treatment, the levels of cytokines and chemokines, including interleukin-1β, interleukin-10, tumor necrosis factor-α, and monocyte chemoattractant protein 1, increased in the Apex1 +/- mice. The Kaplan-Meier curve showed a significant reduction in the survival rates of Apex1 +/- mice treated with LPS compared to those of Apex1 +/+ mice. The hepatic and lung injury scores and Ly6G + neutrophil infiltration levels also increased in Apex1 +/- mice after LPS treatment. These results showed that Apex1 deficiency exacerbated the LPS-induced tissue damage in the lung and liver. These findings illustrate that in vivo Apex1 deficiency exacerbates LPS-induced systemic inflammation, tissue damage, and mortality in a murine model, highlighting the crucial role of Apex1 in mitigating inflammatory responses and maintaining a holistic physiological equilibrium., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pelvic organ prolapse (POP), a downward descent of the vagina and/or uterus through the vaginal canal, is a prevalent condition affecting up to 40% of women. Several risk factors of POP have been identified, including childbirth, connective tissue defects, and chronic intra-abdominal pressure; however, the underlying etiologies of POP development are not fully understood, leading to a high burden on patients and the healthcare systems. The uterosacral ligaments are key support structures of the uterus and upper vagina. Our previous work describes observed histopathological changes in uterosacral ligament (USL) tissue and demonstrates the presence of neutrophils in a subgroup of POP individuals. This presence of neutrophils prompted an examination for the presence of a broader spectrum of inflammatory cell types in the USL. Immunohistochemical staining was performed to identify neutrophils, lymphocytes, macrophages, and mast cells outside of the vasculature. All 4 inflammatory cell types were increased in the POP-HQ system-defined POP-Inflammatory (POP-I) phenotype USL tissue relative to the USL tissues of control or other POP-HQ phenotypes. Focal T-lymphocyte and macrophage co-accumulations were observed in the arterial walls from some patients of the POP-vascular (POP-V) phenotype suggesting previous arterial injury. In addition, 1 control and 2 POP-V subjects' USLs contained arterial wall foamy macrophages, evidence of atherosclerosis. These findings further support a complex etiology for POP and indicate that personalized approaches to preventing and treating the condition may be warranted., (© 2024. The Author(s).)

The CCL2-CCR2 axis is involved in lupus nephritis, however the precise roles in the mechanisms by which different pathological lesions develop after glomerular immune complex deposition remain elusive. Previously, we demonstrated that genetic CCR2 inhibition induced a histological switch from glomerular endocapillary hypercellularity to wire-loop lesions in murine lupus nephritis. This study aimed to clarify the CCL2-CCR2 axis-mediated cellular mechanism in the formation of these different pathological lesions. We injected MRL/lpr mouse-derived monoclonal IgG3 antibody-producing hybridomas, 2B11.3 or B1, into wild-type (WT) mice to selectively induce glomerular endocapillary hypercellularity or wire-loop lesions. The expression of chemokine and chemokine receptors was analyzed using RT-quantitative PCR and/or immunofluorescence. We found 2B11.3 caused glomerular endocapillary hypercellularity in WT mice with glomerular infiltration of larger numbers of CCR2-expressing macrophages and neutrophils phagocyting immune complex, whereas B1 induced wire-loop lesions. In glomerular endocapillary hypercellularity, CCL2 was identified as the ligand involved in the CCR2-positive cell infiltration; it was expressed by glomerular endothelial cells and macrophages. Notably, 2B11.3-induced glomerular endocapillary hypercellularity converted to wire-loop lesions with reduced glomerular macrophage and neutrophil infiltration in CCL2-deficient (Ccl2 -/- ) mice similarly observed in Ccr2 -/- mice. Moreover, this histological conversion was also observed when both glomerular macrophage and neutrophil infiltration were inhibited in anti-Ly6G antibody-treated Ccr5 -/- mice but not when only glomerular macrophage infiltration was inhibited in Ccr5 -/- mice or when only glomerular neutrophil infiltration was inhibited in anti-Ly6G antibody-treated WT mice. In contrast, B1 injection caused wire-loop lesions in Ccl2 -/- and Ccr2 -/- mice, as observed in WT mice. Moreover, 2B11.3 induced CCL2 from glomerular endothelial cells to a larger extent than B1 when injected into Ccr2 -/- mice. In conclusion, the CCL2-CCR2 axis determines whether glomerular endocapillary hypercellularity or wire-loop lesions develop by regulating glomerular infiltration of phagocytic cells: macrophages and neutrophils. © 2024 The Pathological Society of Great Britain and Ireland., (© 2024 The Pathological Society of Great Britain and Ireland.)

Objective: To investigate the clinical value of blood routine derivative biomarkers and thyroid function biomarkers in differentiating different thyroid diseases., Methods: The differences of blood routine derived indexes neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), platelet-large cell rate (P-LCR) and thyroid function indexes between benign and malignant thyroid diseases were compared, and the differences of each index between different benign thyroid diseases were further compared. Univariate regression analysis model was used to analyze the clinical value of various indexes. Receiver operating characteristic curve (ROC) was used to calculate the area under the curve (AUC)., Results: There were statistically significant differences in PLR, NLR and P-LCR between patients with benign and malignant thyroid diseases (P < 0.05 for each). The results of univariate logistic regression analysis showed that P < 0.05 for all indicators except LMR, when PLR and NLR value increased by 1, the risk of thyroid malignancy decreased by 1 % and 21 %, when P-LCR value increased by 1, the risk of thyroid malignancy increased by 4 %., Conclusions: PLR, NLR and P-LCR are helpful to distinguish different benign thyroid diseases and to diagnose benign and malignant thyroid diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Several studies have found that the absolute lymphocyte (ALC) or neutrophil count predicts the survival of patients with solid tumors, and that the neutrophil-to-lymphocyte ratio and the prognostic nutritional index are useful markers of gastric cancer prognosis. However, it remains unclear whether the ALC is prognostic of lymph node (LN) metastasis in patients with gastric cancer. In this study, we aimed to explore the impact of ALC on prognosis and distinctive clinical characteristics in patients with gastric cancer., Patients and Methods: The medical records of patients with gastric adenocarcinomas who underwent radical gastrectomy with curative intent at Seoul St. Mary's Hospital and Yeouido St. Mary's Hospital between January 2010 and December 2017 were reviewed. Of these, 4149 patients for whom preoperative white blood cell, neutrophil, and lymphocyte counts were available were enrolled., Results: In all 4149 patients, ALC gradually decreased as the pN stage increased. Those with an ALC of less than 1360 cells/μL were defined as a low-ALC group, and advanced cT and cN stages were the strongest risk factors for LN metastasis in both univariate and multivariate analyses; undifferentiated tumor histology and a low ALC were also significant risk factors. Patients of all stages in the ALC-low group exhibited poorer prognoses. The ALC-low group also exhibited a higher recurrence rate in a greater proportion of LNs., Conclusions: In patients with gastric cancer, as the preoperative ALC decreases, the incidence of LN metastasis increases. A low ALC is associated with a high recurrence rate, particularly in LNs., (© 2024. Society of Surgical Oncology.)

The molecular signature of cell-derived extracellular vesicles (EVs) from synovial fluid (SF) offers insights into the cells and molecular processes associated with joint disorders and can be exploited to define biomarkers. The EV-signature is determined by cargo molecules and the lesser-studied lipid bilayer. We here investigated the lipidome of SF-EVs in inflamed joints derived from Rheumatoid Arthritis (RA) and Spondyloarthritis (SpA) patients, two autoimmune-driven joint diseases, and compared these signatures to the lipid profile of equine SF-EVs obtained during induced acute synovitis. Since neutrophils are primary SF-infiltrating cells during these inflammatory joint diseases, we also analyzed how inflammatory stimuli alter the lipidomic profile of human and equine neutrophil-derived EVs (nEVs) in vitro and how these signatures relate to the lipidome signatures of SF-EVs from inflamed joints. We identified neutrophil stimulation intensity-dependent changes in the lipidomic profile of nEVs with elevated presence of dihexosylceramide (lactosylceramide), phosphatidylserine, and phosphatidylethanolamine ether-linked lipid classes in human nEVs upon full neutrophil activation. In horses, levels of monohexosylceramide (glucosylceramide) increased instead of dihexosylceramide, indicating species-specific differences. The lipid profiles of RA and SpA SF-EVs were relatively similar and showed a relative resemblance with stimulated human nEVs. Similarly, the lipidome of equine synovitis-derived SF-EVs closer resembled the one of stimulated equine nEVs. Hence, lipidome profiling can provide insights into the contribution of nEVs to the heterogeneous pool of SF-EVs, deepening our understanding of inflammatory joint diseases and revealing molecular changes in joint homeostasis, which can lead to the development of more precise disease diagnosis and treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Central retinal artery occlusion (CRAO) has been identified as an acute emergency resulting in vision loss, with its pathogenesis potentially involving systemic inflammation and abnormal lipid metabolism. Over recent years, it has been established that peripheral blood inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), the systemic immunoinflammatory index (SII), and the monocyte-to-high-density lipoprotein ratio (MHR), play significant roles in assessing systemic inflammation and lipid metabolism. However, the role of these indices in assessing the severity of CRAO has rarely been explored. This study aimd to investigate the relationship between these inflammatory indices and the severity of CRAO., Methods: This was a retrospective clinical study with a total of 49 CRAO patients and 50 age- and sex-matched controls involved. The patients with CRAO were divided into three groups (13 with incomplete CRAO, 16 with subtotal CRAO and 20 with total CRAO). Data were compared across these groups, and additionally, correlation analysis, restricted cubic spline plots, and receiver operating characteristic curve analysis were performed., Results: The values of NLR, SII and MHR were significantly higher in the CRAO group compared to controls (NLR: 2.49(1.71,3.44) vs 1.60(1.24,1.97), P <0.001; SII: 606.46(410.25,864.35) vs 403.91(332.90,524.31), P =0.001; MHR: 0.33(0.26,0.44) vs 0.25(0.21,0.34), P <0.001). MHR was also significantly higher in total CRAO than in incomplete CRAO and subtotal CRAO (0.41(0.32,0.60) vs 0.29(0.21,0.43), P =0.036; 0.41(0.32,0.60) vs 0.29(0.23,0.38), P =0.017). Significant positive associations were found between MHR, NLR, SII and both the incidence (all P <0.001) and severity ( P <0.001, P <0.001, P =0.003, respectively) of CRAO. MHR had a linear relationship with both the occurrence and severity of CRAO (P-overall=0.013, P-non-linear=0.427 and P-overall=0.013, P-non-linear=0.825). Combining MHR and NLR significantly improved diagnostic efficacy for CRAO and total CRAO, with area under the curve of 0.816 and 0.827, respectively, compared to using MHR alone (0.705 and 0.816)., Conclusion: Elevated levels of peripheral blood NLR, SII, and MHR are positively associated with CRAO incidence, highlighting their potential as early predictive markers. The combined NLR and MHR index further enhances diagnostic accuracy and may facilitate timely assessment of CRAO severity by ophthalmologists and internists., Competing Interests: The authors declare there are no competing interests., (©2024 Hu et al.)

Neutrophil extracellular traps (NETs), crucial in immune defense mechanisms, are renowned for their propensity to expel decondensed chromatin embedded with inflammatory proteins. Our comprehension of NETs in pathogen clearance, immune regulation and disease pathogenesis, has grown significantly in recent years. NETs are not only pivotal in the context of infections but also exhibit significant involvement in sterile inflammation. Evidence suggests that excessive accumulation of NETs can result in vessel occlusion, tissue damage, and prolonged inflammatory responses, thereby contributing to the progression and exacerbation of various pathological states. Nevertheless, NETs exhibit dual functionalities in certain pathological contexts. While NETs may act as autoantigens, aggregated NET complexes can function as inflammatory mediators by degrading proinflammatory cytokines and chemokines. The delineation of molecules and signaling pathways governing NET formation aids in refining our appreciation of NETs' role in immune homeostasis, inflammation, autoimmune diseases, metabolic dysregulation, and cancer. In this comprehensive review, we delve into the multifaceted roles of NETs in both homeostasis and disease, whilst discussing their potential as therapeutic targets. Our aim is to enhance the understanding of the intricate functions of NETs across the spectrum from physiology to pathology., (© 2024. The Author(s).)

Abstract: Neutrophils are the first line of defense against invading pathogens. Neutrophils execute and modulate immune responses by generating reactive oxygen species (ROS). Chronic granulomatous disease (CGD) is a primary immune deficiency disorder of phagocytes, caused by inherited mutations in the genes of the nicotinamide adenine dinucleotide phosphate reduced oxidase enzyme. These mutations lead to failure of ROS generation followed by recurrent bacterial and fungal infections, frequently associated with hyperinflammatory manifestations. We report a multicenter cumulative experience in diagnosing and treating patients with CGD. From 1986 to 2021, 2918 patients experiencing frequent infections were referred for neutrophil evaluation. Among them, 110 patients were diagnosed with CGD: 56 of Jewish ancestry, 48 of Arabic ancestry, and 6 of non-Jewish/non-Arabic ancestry. As opposed to other Western countries, the autosomal recessive (AR) CGD subtypes were predominant in Israel (71/110 patients). Thirty-nine patients had X-linked CGD, in most patients associated with severe infections (clinical severity score ≥3) and poor outcomes, presenting at a significantly earlier age than AR-CGD subtypes. The full spectrum of infections and hyperinflammatory manifestations is described. Six patients had hypomorphic mutations with significantly milder phenotype, clinical severity score ≤2, and better outcomes. Hematopoietic stem cell transplantation was implemented in 39 of 110 patients (35.5%). Successful engraftment was achieved in 92%, with 82% long-term survival and 71% full clinical recovery. CGD is a complex disorder requiring a multiprofessional team. Early identification of the genetic mutation is essential for prompt diagnosis, suitable management, and prevention., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Glioma is the most common primary intracranial tumor in adults, with high incidence, recurrence, and mortality rates. Tumor-associated neutrophils (TANs) are essential components of the tumor microenvironment (TME) in glioma and play a crucial role in glioma cell proliferation, invasion and proneural-mesenchymal transition. Besides the interactions between TANs and tumor cells, the multi-dimensional crosstalk between TANs and other components within TME have been reported to participate in glioma progression. More importantly, several therapies targeting TANs have been developed and relevant preclinical and clinical studies have been conducted in cancer therapy. In this review, we introduce the origin of TANs and the functions of TANs in malignant behaviors of glioma, highlighting the microenvironmental regulation of TANs. Moreover, we focus on summarizing the TANs-targeted methods in cancer therapy, aiming to provide insights into the mechanisms and therapeutic opportunities of TANs in the malignant glioma microenvironment., (© 2024. The Author(s).)

Metastasis has been one of the primary reasons for the high mortality rates associated with tumours in recent years, rendering the treatment of current malignancies challenging and representing a significant cause of recurrence in patients who have undergone surgical tumour resection. Halting tumour metastasis has become an essential goal for achieving favourable prognoses following cancer treatment. In recent years, increasing clarity in understanding the mechanisms underlying metastasis has been achieved. The concept of premetastatic niches has gained widespread acceptance, which posits that tumour cells establish a unique microenvironment at distant sites prior to their migration, facilitating their settlement and growth at those locations. Neutrophils serve as crucial constituents of the premetastatic niche, actively shaping its microenvironmental characteristics, which include immunosuppression, inflammation, angiogenesis and extracellular matrix remodelling. These characteristics are intimately associated with the successful engraftment and subsequent progression of tumour cells. As our understanding of the role and significance of neutrophils in the premetastatic niche deepens, leveraging the presence of neutrophils within the premetastatic niche has gradually attracted the interest of researchers as a potential therapeutic target. The focal point of this review revolves around elucidating the involvement of neutrophils in the formation and shaping of the premetastatic niche (PMN), alongside the introduction of emerging therapeutic approaches aimed at impeding cancer metastasis., (© 2024. The Author(s).)

Tumor cells remodel the phenotype and function of tumor microenvironment (TME) cells to favor tumor progression. Previous studies have shown that neutrophils in TME are polarized to N2 tumor-associated neutrophils (TANs) by tumor derived factors, thus promoting tumor growth and metastasis, angiogenesis, therapy resistance, and immunosuppression. Exosomes act as critical intercellular messengers in human health and diseases including cancer. So far, the biological roles of exosomes from N2 TANs in gastric cancer have not been well characterized. Herein, we represented the first report that exosomes from N2 TANs promoted gastric cancer metastasis in vitro and in vivo. We found that exosomes from N2 TANs transferred miR-4745-5p/3911 to gastric cancer cells to downregulate SLIT2 (slit guidance ligand 2) gene expression. Adenovirus-mediated overexpression of SLIT2 reversed the promotion of gastric cancer metastasis by N2 TANs derived exosomes. We further revealed that gastric cancer cells induced glucose metabolic reprogramming in neutrophils through exosomal HMGB1 (high mobility group protein B1)/NF-κB pathway, which mediated neutrophil N2 polarization and miR-4745-5p/3911 upregulation. We further employed ddPCR (droplet digital PCR) to detect the expression of miR-4745-5p/3911 in N2 TANs exosomes from human serum samples and found their increased levels in gastric cancer patients compared to healthy controls and benign gastric disease patients. Conclusively, our results indicate that N2 TANs facilitate cancer metastasis via regulation of SLIT2 in gastric cancer cells by exosomal miR-4745-5p/3911, which provides a new insight into the roles of TME cells derived exosomes in gastric cancer metastasis and offers a potential biomarker for gastric cancer diagnosis., (© 2024. The Author(s).)

Background: This study aims to investigate preoperative prognostic factors available for intrahepatic cholangiocarcinoma (ICC) patients and propose a new preoperative prognostic scoring system for ICC that combines CA19-9 and neutrophil/lymphocyte ratio (NLR)., Methods: In this retrospective analysis, 1728 patients diagnosed with ICC and undergoing curative liver resections were studied. This study employed univariate and multivariate Cox regression to find factors affecting recurrence and overall survival (OS), and furthermore assessed how preoperative models influenced tumor traits and postoperative recurrence., Results: The results of the multivariate Cox regression analysis indicated that two preoperative variables, NLR and Ca19-9, were independent risk factors affecting postoperative recurrence and OS in ICC patients. Based on this data, assigning a score of 0 (NLR ≤ 2.4 and Ca19-9 ≤ 37U/ml) or 1 (NLR > 2.4 and Ca19-9 > 37U/ml) to these two factors, a preoperative prognostic score was derived. According to the scoring model, patients were divided into three groups: 0 points (low-risk group), 1 point (intermediate-risk group), and 2 points (high-risk group). The 5-year recurrence and OS rates for the three groups were 56.6%, 68.2%, 77.8%, and 56.8%, 40.6%, 27.6%, respectively, with all P values < 0.001. Furthermore, high-risk group patients were more prone to early recurrence (early recurrence rates for high-, intermediate-, and low-risk groups were 56.8%, 51.5%, and 37.1%, respectively, P < 0.001) and extrahepatic metastasis (extrahepatic metastasis rates for high-, intermediate-, and low-risk groups were 31.7%, 26.4%, and 15.4%, respectively, P < 0.001). In terms of tumor characteristics, high-risk group patients had larger tumor diameters and were more likely to experience microvascular invasion, lymph node metastasis, and perineural invasion., Conclusions: The predictive capacity of postoperative recurrence and OS rates in ICC patients is effectively captured by the preoperative scoring system incorporating NLR and CA19-9 levels., (© 2024. The Author(s).)

Immune activation status determines non-small cell lung cancer (NSCLC) prognosis, with reported positive/negative associations for T helper type 2 (TH2) responses, including allergen-specific IgE and eosinophils. Our study seeks to explore the potential impact of these comorbid immune responses on the survival rates of patients with NSCLC. Our retrospective study used data from the Data Warehouse of the German Center for Lung Research (DZL) and Lung Biobank at Thoraxklinik Heidelberg. We estimated the association of blood eosinophilia and neutrophilia on survival rates in an inflammatory cohort of 3143 patients with NSCLC. We also tested sensitization to food and inhalants and high-sensitivity C-reactive protein (hs-CRP) in a comorbidity cohort of 212 patients with NSCLC. Finally, we estimated the infiltration of immune-relevant cells including eosinophils, T-cells, and mast cells in a tissue inflammatory sub-cohort of 60 patients with NSCLC. Sensitization to at least one food or inhalant (sIgE) was higher in patients with adenocarcinoma (adeno-LC) than the non-adenocarcinoma (non-adeno-LC). Furthermore, hs-CRP was higher in non-adeno-LC compared with adeno-LC. Peripheral inflammation, particularly eosinophilia and neutrophilia, was associated with poor survival outcomes in NSCLC with a clear difference between histological subgroups. Finally, blood eosinophilia was paralleled by significant eosinophil infiltration into the peritumoral tissue in the lung. This study provides novel perspectives on the crucial role of peripheral inflammation, featuring eosinophilia and neutrophilia, with overall survival, underscoring distinctions between NSCLC subgroups (adeno-LC vs. non-adeno-LC). Peripheral eosinophilia enhances eosinophil infiltration into tumors. This sheds light on the complex interplay between inflammation, eosinophil infiltration, and NSCLC prognosis among various histological subtypes. Further studies are required to underscore the role of eosinophils in NSCLC among different histological subgroups and their role in shaping the tumor microenvironment.

The aim of this study was to evaluate the prognostic value of peripheral blood inflammation indexes in patients with metastatic Colorectal Cancer (CRC) and to establish a predictive scoring system. A total of 324 CRC patients diagnosed through pathological examination from January 2017 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were included. The prognosis of patients with metastatic CRC was examined, and the correlation between IL-10 expression in pathological tissues and IL-10 expression in serum was analyzed. The results showed that the prognosis of CRC was poorer when metastasis occurred (P < 0.001). Additionally, IL-10 was highly expressed in the metastatic CRC group (P = 0.018), and the expression of IL-10 in pathological tissues of patients with metastatic CRC was positively correlated with the expression of IL-10 in serum (P = 0.037). The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-white blood cell ratio (LWR), aggregate index of systemic inflammation (AISI), monocyte-to-lymphocyte ratio (MLR), systemic inflammatory response index (SIRI), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and interleukin-10 (IL-10) were calculated and determined by ROC curve. The critical values were 2.135, 3.735, 353.745, 0.265, 1.025, 52.975, 353.635, and 11.25, respectively. Inflammatory indexes with an AUC of more than 0.6 were selected, and each colorectal cancer patient with any of these risk factors was assigned a score of one. The 324 patients were then divided into two groups: 0-4 for the low-risk group and 4-8 for the high-risk group. The occurrence of distant metastases in the two groups was statistically analyzed. The results showed that the OS and PFS of the low-risk group were significantly superior to those of the high-risk group (P < 0.05). These findings indicate that NLR, LWR, AISI, MLR, SIRI, PNI, ALI, and IL-10 are risk factors for distant metastasis in CRC patients. Therefore, the prediction scores of these indexes can be used to effectively evaluate the prognosis of patients with metastatic CRC., (© 2024. The Author(s).)

Objective: To study the kinetics of blood count nadir and time to recovery and find its association with clinical outcomes in a cohort of Acute Lymphoblastic Leukemia (ALL)., Methods: Data from 243 cases treated between January 2018 to December 2020 was retrospectively analysed. Along with baseline data, serial measures of peripheral blood counts, nadir, and time to partial and complete recovery of counts during course of induction chemotherapy were recorded. Post-induction Complete Remission (CR) status, Event-Free Survival (EFS) , and Overall Survival (OS) were recorded as clinical outcomes for analysis., Results: Median age was 15 (range,1-62) years. Immunophenotype was B-ALL in 71% (n=172), and T-ALL in 27% (n=66). Good steroid response (D8) was seen in 89%(n=216), CR in 79% (n=192), and induction mortality in 12% (n=29). Median neutrophil nadir was 0.06(0-0.49) *10⁹/L and median day to nadir was D17. Median time to partial and complete platelet recovery was D18 and D25. Late neutrophil nadir (>D15) was independent predictor of refractory disease post-induction [OR=5.43 (95%CI 1.06-27.75)]. Late partial platelet recovery (>D22) was independent predictor of poorer EFS and OS [HR = 1.63 (95%CI 1.07-2.47)] and [HR = 1.5 (95% CI 1-2.4)] respectively., Conclusion: We found that a longer time to neutrophil nadir independently predicts refractory disease post-induction and late partial platelet recovery is an independent factor for poorer EFS and OS. Thus, Blood count kinetics as independent predictors of induction outcomes can provide a simple, easy-to-use tool for balancing toxicity-efficacy during induction therapy for ALL.

Objective: To investigate markers of systemic inflammation and the effect of thyroid dysfunction on these parameters in patients with Hashimoto's thyroiditis (HT)., Methods: Patients with HT and volunteer healthy individuals admitted to the general surgery outpatient clinic between January 2020 and June 2023 were enrolled into the study. Patients with HT were divided into euthyroid, hypothyroid, and hyperthyroid subgroups. All participant data were retrospectively extracted from the hospital database., Results: A total of 268 patients (euthyroid, n  = 131; hypothyroid, n  = 83; and hyperthyroid, n  = 54) and 124 controls were included. The platelet-to-lymphocyte ratio was lower in the euthyroid group versus control group, and the neutrophil-to-lymphocyte ratio was lower in controls than the three patient subgroups. Euthyroid and hypothyroid patients with HT exhibited a higher systemic inflammation index than the control group. The pan-immune inflammation index was lower in controls than in euthyroid, hypothyroid, and hyperthyroid patients with HT. In patients with HT, inflammation markers did not significantly differ between subgroups., Conclusions: Markers of systemic inflammation provide meaningful and reliable information in patients with HT, but do not differentiate between euthyroid, hypothyroid, or hyperthyroid patients., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflicts of interest.

Objective: To analyze the predictive value of the triglyceride-glucose (TyG) index and neutrophil-to-high-density lipoprotein ratio (NHR) for in-hospital major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI), and to establish an associated nomogram model., Methods: In this retrospective study, we collected data from consecutive STEMI patients who underwent PCI from October 2019 to June 2023 at the Second People's Hospital of Hefei and the Second Affiliated Hospital of Anhui Medical University, as training and validation sets. Stepwise regression and multivariate logistic regression analysis were performed to screen independent risk factors, and a nomogram model was constructed and evaluated for its predictive efficacy., Results: The TyG index, NHR, urea, diastolic blood pressure, hypertension, and left ventricular ejection fraction were independent risk factors for in-hospital MACE after PCI, and were used to construct the nomogram model. The C-index of the training and validation sets were 0.799 and 0.753, respectively, suggesting that the model discriminated well. Calibration and clinical decision curves also demonstrated that the nomogram model had good predictive power., Conclusion: In STEMI patients, increased TyG index and NHR were closely related to the occurrence of in-hospital MACE after PCI. Our constructed nomogram model has some value for predicting the occurrence of in-hospital MACE in STEMI patients., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Background/aim: The predictive role of hematological markers in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) treated with pembrolizumab remains unclear., Patients and Methods: We conducted a multicenter retrospective cohort study to investigate the predictive impact of the pre-treatment hematological markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), CRP-albumin-lymphocyte (CALLY) index, and the modified Glasgow prognostic score (mGPS) on overall survival (OS) and progression-free survival (PFS) in patients with R/M SCCHN treated with pembrolizumab. From December 2019 to February 2022, 119 and 28 patients were treated with pembrolizumab alone and pembrolizumab plus chemotherapy, respectively. The optimal cut-off point of dichotomized hematological markers was calculated using the area under the receiver operating characteristic curve. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders., Results: In the pembrolizumab monotherapy group, patients with higher NLR, PLR, and mGPS and a lower CALLY index showed significantly shorter OS after adjustment for potential confounders. In addition, all hematological markers examined in this study tended to be associated with clinical response, such as overall response rate or disease control rate (DCR); in particular, a lower CALLY index and higher mGPS were significantly associated with poor DCR. In the pembrolizumab with chemotherapy group, these hematological markers had a similar association with OS but not with clinical response., Conclusion: Pre-treatment NLR, PLR, CALLY index, and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with pembrolizumab., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: In patients with recurrent glioblastoma, very little data are available regarding the prognostic value of platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte (NLR) ratios. This study investigated potential associations between PLR or NLR and treatment outcomes., Patients and Methods: PLR and NLR at diagnosis of recurrence plus 10 additional characteristics were retrospectively analyzed for associations with progression-free survival (PFS) and overall survival (OS) in 75 patients with recurrent glioblastoma., Results: On multivariate analyses, maximal cumulative diameter of recurrent lesion(s) <40 mm (p=0.015) and systemic therapy (p<0.001) were associated with improved PFS. On multivariate analysis of OS, improved outcomes were significantly associated with PLR ≤150 (p=0.029), maximal cumulative diameter <40 mm (p=0.030), and systemic therapy (p=0.010)., Conclusion: In addition to other characteristics, PLR at the time of recurrence was identified as an independent predictor of OS in patients with recurrent glioblastoma. PLR may be useful when designing personalized treatment approaches or clinical trials., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Prior research in non-small cell lung cancer (NSCLC) has shown that tumors with specific driver mutations may be less likely to respond to immune checkpoint inhibitors (ICI). In this analysis, we evaluated the characteristics of patients with durable clinical benefit (DCB) to ICI compared to those with no durable clinical benefit (NDB), with emphasis on the role of molecular alterations in EGFR, ALK, and ROS1 and pretreatment neutrophil-to-lymphocyte ratio (NLR)., Methods: We retrospectively collected clinical characteristics and outcomes for patients who initiated ICI monotherapy for advanced NSCLC at Stanford University between April 2015 and May 2018. Patients were classified as having DCB if time on ICI therapy was greater than or equal to 180 days, or NDB if less than 180 days. Outcomes included best radiographic benefit while on ICI and survival from time of ICI initiation., Results: Of 123 patients treated with ICI for NSCLC, 28 patients had DCB (23%), while 95 had NDB (77%). Median overall survival from initiation of ICI in the 33 patients with molecular alterations in EGFR (n = 31), ALK, or ROS1 and NLR of 5.9 or higher was 2.0 months, compared to 8.1 months in patients with these genomic alterations and NLR less than 5.9. Median overall survival in patients without alterations in EGFR, ALK, or ROS1 and NLR of 5.9 or higher was 4.3 months, compared to 12.1 months in patients with NLR less than 5.9 (P = .023)., Conclusions: Elevation in pretreatment NLR was associated with significantly lower overall median survival from initiation of ICI, particularly when in combination with NSCLC with alterations in EGFR, ALK, or ROS1. This finding could influence clinical practice as NLR is readily available through routine blood testing., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Several inflammatory markers have gained interest as prognostic factors for cancer. The aim of this study is to evaluate the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as predictive markers for aggressive behavior and early recurrences in primary, localized soft tissue sarcoma (STS)., Methods: 115 STS patients were retrospectively reviewed. IL-6 and CRP blood levels, NLR and PLR were obtained prior to treatment. Early recurrence was defined as disease relapse (local or distant) within the first year after surgery. Cox regression analysis was used to identify prognostic factors for early recurrence., Results: IL-6 elevation was associated with a higher tumor grade, increased size, tumor necrosis and a higher mitotic count. NLR elevation was associated with a higher tumor grade, PLR elevation with a larger tumor size. Early recurrences were found in 24 patients (21 %). Univariable analysis revealed that tumor grade (p = 0.029), tumor size (p = 0.030, >10 cm vs < 5 cm), tumor depth (p = 0.036), necrosis on imaging (p = 0.008), mitotic count (p = 0.045, ≥20 mitoses vs 0-9 mitoses), and IL-6 level (p = 0.044) were associated with early recurrence. The factors age at diagnosis, tumor location, necrosis at pathology, (neo)adjuvant radio- or chemotherapy, resection margin, CRP level, NLR and PLR were not related to early disease recurrence., Conclusions: Increased inflammatory markers in STS are associated with an aggressive phenotype. STS patients with elevation of IL-6 may be at risk for early disease recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The diagnostic accuracy of suspicious lesions that are classified as PI-RADS 3 in multiparametric prostate magnetic-resonance imaging (mpMRI) is controversial. This study aims to assess the predictive capacity of hematological inflammatory markers such as neutrophil-lymphocyte ratio (NLR), pan-immune-inflammation value (PIV), and systemic immune-response index (SIRI) in detecting prostate cancer in PI-RADS 3 lesions., Methods: 276 patients who underwent mpMRI and subsequent prostate biopsy after PI-RADS 3 lesion detection were included in the study. According to the biopsy results, the patients were distributed to two groups as prostate cancer (PCa) and no cancer (non-PCa). Data concerning age, PSA, prostate volume, PSA density, PI-RADS 3 lesion size, prostate biopsy results, monocyte counts (10 9 /L), lymphocyte counts (10 9 /L), platelet counts (10 9 /L), neutrophils count (10 9 /L) were recorded from the complete blood count. From these data; PIV value is obtained by monocyte × neutrophil × platelet/lymphocyte, NLR by neutrophil/lymphocyte, and SIRI by monocyte number × NLR., Results: Significant variations in neutrophil, lymphocyte, and monocyte levels between PCa and non-PCa patient groups were detected (p = 0.009, p = 0.001, p = 0.005 respectively, p < 0.05). NLR, PIV, and SIRI exhibited significant differences, with higher values in PCa patients (p = 0.004, p = 0.001, p < 0.001 respectively, p < 0.05). The area under curve of SIRI was 0.729, with a cut-off value of 1.20 and with a sensitivity 57.70%, and a specificity of 68.70%., Conclusion: SIRI outperformed NLR and PIV in detecting PCa in PI-RADS 3 lesions, showcasing its potential as a valuable biomarker. Implementation of this parameter to possible future nomograms has the potential to individualize and risk-stratify the patients in prostate biopsy decision., (© 2024 Wiley Periodicals LLC.)

Introduction: Compare scoring systems using Fournier gangrene severity index (FGSI), Uludag Fournier gangrene severity index (UFGSI), Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC), and neutrophil-lymphocyte ratio (NLR) to predict the outcome of patients with Fournier gangrene., Materials and Methods: This is a retrospective cohort study that includes FG patients from 2012 to 2021. NLR, FGSI, UFGSI, and LRINEC values were calculated and analyzed. Each scoring system was analyzed using a receiver-operating curve (ROC) analysis to determine its sensitivity, specificity, and area under the curve (AUC). Statistical analysis was performed using SPSS version 25., Results: A total of 158 patients were included in this study. Regarding the mortality outcome, FGSI comprised the highest value of AUC with 80.9, with a sensitivity of 91.7% and specificity of 68.5%. LRINEC comprised the AUC value of 61.1, with 79.2% sensitivity and 64.2% specificity. NLR comprised an AUC value of 63.7, 91.7% of sensitivity, and 98.1% of specificity. In terms of length of stay, LRINEC and NLR were associated as significant predictor., Conclusion: FGSI, UFGSI, and NLR are significant predictors associated with mortality in patients with Fournier gangrene. FGSI and UFGSI comprised the highest sensitivity and specificity value in predicting mortality prognosis. Moreover, this study highlighted the role of NLR and LRINEC as significant predictors for the length of hospitalization. This study shows that FGSI is still a reliable scoring system for predicting mortality in patients with Fournier Gangrene., Level of Evidence: II., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objective: Recently, the nuclear area has attracted attention as a morphological parameter to differentiate high-grade urothelial carcinoma (HGUC) cells from benign reactive cells. The nuclear long diameter (NLD) strongly correlates with the nuclear area and is easy to subjectively estimate. Therefore, this study examined the usefulness of the NLD-to-neutrophil diameter ratio for detecting HGUC cells in urine cytology., Methods: This study included 29, 26 and 18 patients with HGUC, glomerular disease and urolithiasis respectively. An image analysis system was used to measure the NLD of HGUC and benign reactive cells (reactive renal tubular cells and reactive urothelial cells) and the neutrophil diameter that appeared in the voided urine in these cases. The NLD index was calculated using the NLD-to-neutrophil diameter ratio. We subsequently compared HGUC and benign reactive cells with respect to NLD and NLD indices. In addition, the HGUC cell group and benign reactive cell group were compared by selecting the five cells with the largest NLD and NLD index on each slide., Results: The NLD and NLD indices of HGUC cells were significantly higher than those of benign reactive cells in all cells and in the five cells with the largest NLD and NLD indices. The cut-off value of the NLD index for detecting HGUC cells was 1.25 in all cells and 1.80 in the five cells with the largest NLD index., Conclusions: The NLD index is a useful parameter that can be introduced into routine microscopic examinations to differentiate HGUC cells from benign reactive cells., (© 2024 John Wiley & Sons Ltd.)

Characterization of inflammation in chronic rhinosinusitis with (CRSwNP) and without nasal polyps (CRSsNP) is an ongoing research process. To overcome limitations of current cytologic techniques, we investigated whether immunofluorescence multiplex image cytometry could quantify intact neutrophils, eosinophils, and other immune cells in solid upper airway mucosa. We used a four-channel immunofluorescence-microscopy technique for the simultaneous detection of the leukocyte marker CD45, the neutrophil marker myeloperoxidase, two eosinophil markers, i.e., major basic protein and eosinophil peroxidase, and DAPI (4',6-diamidin-2-phenylindole), in formalin-fixed paraffin-embedded upper airway tissue samples of patients with CRSwNP and CRSsNP, as well as of patients free of CRS with inferior turbinate hypertrophy (controls). Image acquisition and analysis were performed with TissueFAXS and StrataQuest (TissueGnostics, Vienna, Austria), respectively. Positive and negative immunostaining were differentiated with a specific fluorescence signal/background signal ratio. Isotype controls were used as negative controls. In six controls, nine patients with CRSsNP, and 11 patients with CRSwNP, the median area scanned and median cell count per patient were 14.2 mm 2 and 34,356, respectively. In CRSwNP, the number of eosinophils was three times higher (23%) than that of neutrophils (7%). Three times more immune cells were encountered in CRSwNP (33%) compared to CRSsNP (11%). In controls, inflammation was balanced between the epithelial layer and lamina propria, in contrast to CRS (three times more pronounced inflammation in the lamina propria). The quantification of intact neutrophils, eosinophils, and other immune cells in solid tissue with undisrupted architecture seems feasible with immunofluorescence multiplex image cytometry., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neutrophil extracellular traps (NETs) are network-like structures released by activated neutrophils. They consist mainly of double-stranded DNA, histones, and neutrophil granule proteins. Continuous release of NETs in response to external stimuli leads to activation of surrounding platelets and monocytes/macrophages, resulting in damage to endothelial cells (EC) and vascular smooth muscle cells (VSMC). Some clinical trials have demonstrated the association between NETs and the severity and prognosis of atherosclerosis. Furthermore, experimental findings have shed light on the molecular mechanisms by which NETs contribute to atherogenesis. NETs play a significant role in the formation of atherosclerotic plaques. This review focuses on recent advancements in the understanding of the relationship between NETs and atherosclerosis. It explores various aspects, including the formation of NETs in atherosclerosis, clinical trials investigating NET-induced atherosclerosis, the mechanisms by which NETs promote atherogenesis, and the translational implications of NETs. Ultimately, we aim to propose new research directions for the diagnosis and treatment of atherosclerosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study explored the utility of NLR (neutrophil-to-lymphocyte ratio) as a marker to predict Lower Extremity Peripheral Artery Disease (PAD) in the Chinese population, as well as to assess its consistency and diagnostic value with digital subtraction angiography., Methods: Patients were distributed into three groups according to the angiography in lower limb arterial: group L1, plaque with no stenosis; group L2, plaque with luminal stenosis and group L3, total vascular occlusion. Changes in the neutrophil-to-lymphocyte ratio were documented and compared among groups., Results: Compared to group L1, NLR was significantly increased in L2 (1.76 vs 2.35, p =0.037) and L3 (1.76 vs 3.60, p< 0.001), with a gradual decrease in ABI (Ankle-Brachial Index, 1.11 vs 1.02 vs 0.94, p< 0.001). Those older patients with higher prevalence of hypertension ( p =0.002), obesity ( p =0.032), or reduced high-density lipoprotein cholesterol ( p =0.020) were more likely to develop PAD; higher glycosylated hemoglobin ( p =0.045), low-density lipoprotein cholesterol ( p =0.006), and systolic blood pressure ( p< 0.001) levels led to a greater tendency to suffer stenosis or even occlusion; the probability of severe stenosis (>70%) increased to 2.075 times for every 1 increase in NLR, while it was 46.8% for every 0.1 increase in ABI. The optimal NLR cut-off value to predict severe stenosis in PAD was 2.73. Receiver operating characteristic curve analysis of the inflammatory biomarkers and severe stenosis prediction displayed an area under the curve of 0.81., Conclusion: NLR could serve as a new noninvasive and accurate marker in predicting PAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wang, Jia, Jiang, Yang, Wang and Zhang.)

Background: Neutrophil extracellular traps (NETs) induce oxidative stress, which may initiate ferroptosis, an iron-dependent programmed cell death, during abdominal aortic aneurysm (AAA) formation. Mitochondria regulate the progression of ferroptosis, which is characterized by the depletion of mitochondrial glutathione (mitoGSH) levels. However, the mechanisms are poorly understood. This study examined the role of mitoGSH in regulating NET-induced ferroptosis of smooth muscle cells (SMCs) during AAA formation., Methods: Concentrations of NET markers were tested in plasma samples. Western blotting and immunofluorescent staining were performed to detect the expression and localization of NET and ferroptosis markers in tissue samples. The role of NETs and SMC ferroptosis during AAA formation was investigated using peptidyl arginine deiminase 4 gene (Padi4) knockout or treatment with a PAD4 inhibitor, ferroptosis inhibitor or activator in an angiotensin II-induced AAA mouse model. The regulatory effect of SLC25A11, a mitochondrial glutathione transporter, on mitoGSH and NET-induced ferroptosis of SMCs was investigated using in vitro and in vivo experiments. Transmission electron microscopy was used to detect mitochondrial damage. Blue native polyacrylamide gel electrophoresis was used to analyze the dimeric and monomeric forms of the protein., Results: Significantly elevated levels of NETosis and ferroptosis markers in aortic tissue samples were observed during AAA formation. Specifically, NETs promoted AAA formation by inducing ferroptosis of SMCs. Subsequently, SLC25A11 was identified as a potential biomarker for evaluating the clinical prognosis of patients with AAA. Furthermore, NETs decreased the stability and dimerization of SLC25A11, leading to the depletion of mitoGSH. This depletion induced the ferroptosis of SMCs and promoted AAA formation., Conclusion: During AAA formation, NETs regulate the stability of the mitochondrial carrier protein SLC25A11, leading to the depletion of mitoGSH and subsequent activation of NET-induced ferroptosis of SMCs. Preventing mitoGSH depletion and ferroptosis in SMCs is a potential strategy for treating AAA., Competing Interests: Conflict of interest The authors have declared no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Peritoneal washing cytology (CY) in patients with pancreatic cancer is mainly used for staging; however, it may also be used to evaluate the intraperitoneal status to predict a more accurate prognosis. Here, we investigated the potential of deep learning of CY specimen images for predicting the 1-year prognosis of pancreatic cancer in CY-positive patients. CY specimens from 88 patients with prognostic information were retrospectively analyzed. CY specimens scanned by the whole slide imaging device were segmented and subjected to deep learning with a Vision Transformer (ViT) and a Convolutional Neural Network (CNN). The results indicated that ViT and CNN predicted the 1-year prognosis from scanned images with accuracies of 0.8056 and 0.8009 in the area under the curve of the receiver operating characteristic curves, respectively. Patients predicted to survive 1 year or more by ViT showed significantly longer survivals by Kaplan-Meier analyses. The cell nuclei found to have a negative prognostic impact by ViT appeared to be neutrophils. Our results indicate that AI-mediated analysis of CY specimens can successfully predict the 1-year prognosis of patients with pancreatic cancer positive for CY. Intraperitoneal neutrophils may be a novel prognostic marker and therapeutic target for CY-positive patients with pancreatic cancer., (© 2024. The Author(s).)

The objective of this investigation was to analyse the correlation between the neutrophil-to-lymphocyte ratio (NLR) status in the immune microenvironment (IME) and the prognostic outcomes of patients who have undergone radical surgery for colorectal cancer (CRC). In light of the continued prevalence of CRC in China, this study utilised Kaplan-Meier and Cox regression analyses to assess the prognostic relevance of NLR status in IME among patients with CRC. Furthermore, cellular experiments, such as cell scratching, were conducted to elucidate the underlying mechanisms of NLR's impact on CRC. The NLR status in IME has been found to have a significant impact on the prognosis of patients with CRC. Patients who exhibit elevated intratumoural and extratumoural NLR are associated with a poor prognosis. Experimental evidence indicates that tumour-associated neutrophil (TAN) augments the migratory, invasive, and proliferative potential of HT-29, HCT-116 and LOVO colorectal cancer cells, while concurrently reducing their sensitivity to oxaliplatin. Conversely, lymphocytes have demonstrated cytotoxic effects on HT-29 cells. The NLR status in IME may serve as a prognostic biomarker for resectable CRC., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Background: T-LAK cell-oriented protein kinase (TOPK) strongly promotes the malignant proliferation of cancer cells and is recognized as a promising biomarker of tumor progression. Psoriasis is a common inflammatory skin disease featured by excessive proliferation of keratinocytes. Although we have previously reported that topically inhibiting TOPK suppressed psoriatic manifestations in psoriasis-like model mice, the exact role of TOPK in psoriatic inflammation and the underlying mechanism remains elusive., Methods: GEO datasets were analyzed to investigate the association of TOPK with psoriasis. Skin immunohistochemical (IHC) staining was performed to clarify the major cells expressing TOPK. TOPK conditional knockout (cko) mice were used to investigate the role of TOPK-specific deletion in IMQ-induced psoriasis-like dermatitis in mice. Flow cytometry was used to analyze the alteration of psoriasis-related immune cells in the lesional skin. Next, the M5-induced psoriasis cell model was used to identify the potential mechanism by RNA-seq, RT-RCR, and western blotting. Finally, the neutrophil-neutralizing antibody was used to confirm the relationship between TOPK and neutrophils in psoriasis-like dermatitis in mice., Results: We found that TOPK levels were strongly associated with the progression of psoriasis. TOPK was predominantly increased in the epidermal keratinocytes of psoriatic lesions, and conditional knockout of TOPK in keratinocytes suppressed neutrophils infiltration and attenuated psoriatic inflammation. Neutrophils deletion by neutralizing antibody greatly diminished the suppressive effect of TOPK cko in psoriasis-like dermatitis in mice. In addition, topical application of TOPK inhibitor OTS514 effectively attenuated already-established psoriasis-like dermatitis in mice. Mechanismly, RNA-seq revealed that TOPK regulated the expression of some genes in the IL-17 signaling pathway, such as neutrophils chemokines CXCL1, CXCL2, and CXCL8. TOPK modulated the expression of neutrophils chemokines via activating transcription factors STAT3 and NF-κB p65 in keratinocytes, thereby promoting neutrophils infiltration and psoriasis progression., Conclusions: This study identified a crucial role of TOPK in psoriasis by regulating neutrophils infiltration, providing new insights into the pathogenesis of psoriasis., (© 2024. The Author(s).)