Human head-neck model and its application thresholds: a narrative review.

There had been many studies on human head-neck biomechanical models in the last two decades, and the associated modelling techniques were constantly evolving at the same time. Computational approaches had been widely leveraged, in parallel to conventional physical tests, to investigate biomechanics and injuries of the head-neck system in the fields like automotive industry, orthopaedic, sports medicine, etc. The purpose of this manuscript is to provide a global review of the existing knowledge related to the modelling approaches, structural and biomechanical characteristics, validation and application of the present head-neck models. This endeavor aims to support further enhancements and validations in modeling practices, particularly addressing the lack of data for model validation, as well as to prospect the future advances in terms of the topics. Seventy-four models subject to the proposed selection criteria are considered. Based on previously established and validated head-neck computational models, most of the studies performed in-depth investigations of included cases, which revolved around four specific subjects: physio-pathology, treatment evaluation, collision condition, and sports injury. Through the review of the recent 20 years research, the summarized modeling information indicated existing deficiencies and future research topics, as well as provided references for subsequent head-neck model development and application.

Investigation on vehicle occupant dummy applicability for under-foot impact loading conditions.

PURPOSE: Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in under-foot impact loading environments. METHODS: The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures. RESULTS: The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 KN) is still 312.5% that of human active lower limb's (2.4 KN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model. CONCLUSION: Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability.

Development of a finite element full spine model with active muscles for quantitatively analyzing sarcopenia effects on lumbar load.

BACKGROUND AND OBJECTIVE: The musculoskeletal imbalance caused by disease is one of the most critical factors leading to spinal injuries, like sarcopenia. However, the effects of musculoskeletal imbalances on the spine are difficult to quantitatively investigate. Thus, a complete finite element spinal model was established to analyze the effects of musculoskeletal imbalance, especially concerning sarcopenia. METHODS: A finite element spinal model with active muscles surrounding the vertebrae was established and validated from anatomic verification to the whole spine model in dynamic loading at multiple levels. It was then coupled with the previously developed neuromuscular model to quantitatively analyze the effects of erector spinae (ES) and multifidus (MF) sarcopenia on spinal tissues. The severity of the sarcopenia was classified into three levels by changing the physiological cross-sectional area (PCSA) of ES and MF, which were mild (60% PCSA of ES and MF), moderate (48% PCSA of ES and MF), and severe (36% PCSA of ES and MF). RESULTS: The stress and strain levels of most lumbar tissues in the sarcopenia models were more significant than those of the normal model during spinal extension movement. The sarcopenia caused load concentration in several specific regions. The stress level of the L4-L5 intervertebral disc and L1 vertebra significantly increased with the severity of sarcopenia and showed relatively larger values than other segments. From the normal model to a severe sarcopenia model, the stress value of the L4-L5 intervertebral disc and L1 vertebra increased by 128% and 113%, respectively. The strain level of L5-S1 also inclined significantly with the severity of sarcopenia, and the relatively larger capsule strain values occurred at lower back segments from L3 to S1. CONCLUSIONS: In summary, the validated spinal coupling model can be used for spinal injury risk analysis caused by musculoskeletal imbalance. The results suggested that sarcopenia can primarily lead to high injury risk of the L4-L5 intervertebral disc, L1 vertebrae, and L3-S1 joint capsule regarding significant stress or strain variance.

Effect of hip flexion angle on lower limb injuries of occupants in autonomous vehicle crashes.

This study aims to determine the influence of the hip flexion angle on the injury trends of lower limbs. An impact model was established using a hybrid human body model and an accurate vehicle model. Simulations were performed in two boundary environments of 25 and 40% overlap impacts under different hip flexion angles. The analysis of the dynamic responses indicated that the hip flexion angle significantly affected the injury trends. The maximum femur index of different overlaps was all found at the minimum hip angle, except for the left femur at 25% overlap rate. Meanwhile, the maximum acetabular stress was all found at the minimum hip angle (approximately 0.09-0.20 GPa). This study provides mechanistic insights into the lower limb injuries associated with complex human postures.

Neutrophil-to-lymphocyte and hypopharyngeal cancer prognosis: System review and meta-analysis.

Several studies have reported the value of neutrophil-to-lymphocyte ratio (NLR) for the prognosis of hypopharyngeal cancer. However, contradictory findings have also been published. We aimed to clarify the effect of NLR on the prognosis of hypopharyngeal cancer through meta-analysis. Systematic search of PubMed and other database with study selection and data extraction. The combined hazard ratio (HR) and 95% confidence intervals (CI) were calculated using STATA, applying either a fixed-effects or random-effects model. Meta-regression, subgroup analysis, and sensitivity analysis were used to analyze sources of heterogeneity. Publication bias were also assessed. This meta-analysis included 2232 patients with hypopharyngeal cancer from seven studies. The combined HR (OS, HR = 1.80, 95CI%, 1.14-2.82; PFS, HR = 1.88, 95CI%, 1.26-2.79) suggested that high NLR was associated with poor overall survival (OS) and progression-free survival (PFS). Pretreatment NLR can be used as an effective serological indicator to assess the prognosis of patients with hypopharyngeal cancer.

Factors of suicidal behavior among inpatients with major depressive disorder: A retrospective case series.

Objective: Previous studies indicate that more than half of those who died by suicide had a depressive disorder. When discussing the factors associated to suicidal behavior (SB) among patients with major depressive disorder (MDD), sociocultural contexts should also be carefully considered. This case series study explored the factors correlated to SB among MDD patients in Beijing, China. Methods: The patient information sheets were retrieved from an electronic database that comprised patient medical information. Three forms of binary logistic regression equations were conducted to explore the factors associated to SB among patients with MDD. For the inconsistent variables produced by the three regression models, the propensity score matching (PSM) analysis was done for further verification. Results: In this retrospective study, 1,091 depressed cases were enrolled. The difference between the SB group and non-SB group in gender, impulsivity, the severity of depression, history of major mental trauma, and family history of suicide were statistically significant in univariate comparisons (P < 0.05); the binary logistic regression analysis and the PSM analysis showed that female gender, history of major mental trauma, impulsivity, family history of suicide and severity of depression were factors correlated to SB among patients with MDD (odds ratios >1). Conclusions: Female gender, the history of major mental trauma, impulsivity, the severity of depression, and family history of suicide were independently associated with the appearance of SB among MDD patients in Beijing, China. Inevitably, these findings should be viewed with particular caution due to the inherent drawbacks of a retrospective nature. More prospective longitudinal research should be conducted to examine those dynamic alterations in the corresponding confounders.

Post COVID-19 mental health symptoms and quality of life among COVID-19 frontline clinicians: a comparative study using propensity score matching approach.

BACKGROUND: The extent and severity of post-COVID-19 mental health symptoms among frontline clinicians are not clear. This study compared mental health symptoms (i.e., depression, anxiety, and insomnia symptoms) and global quality of life (QOL) after the first COVID-19 outbreak between the COVID-19 treating and non-COVID-19 treating frontline clinicians. METHODS: This cross-sectional, comparative, convenient-sampling study was conducted between October 13 and 22, 2020, which was five months after the first COVID-19 outbreak in China was brought under control. The severity of depression, anxiety, insomnia symptoms, and global QOL of the clinicians were assessed using the Patient Health Questionnaire-9 items (PHQ-9), Generalized Anxiety Disorder Scale-7 items (GAD-7), Insomnia Severity Index (ISI), and the World Health Organization Quality of Life Questionnaire-brief version (WHOQOL-BREF), respectively. The propensity score matching (PSM) method was used to identify comparable COVID-19 treating and non-COVID-19 treating frontline clinicians. A generalized linear model (GLM) was used to assess the differences in PHQ-9, GAD-7, ISI, and QOL scores between the COVID-19 treating and non-COVID-19 treating frontline clinicians. RESULTS: In total, 260 COVID-19 treating frontline clinicians and 260 matched non- COVID-19 treating frontline clinicians were included. Non-COVID-19 treating frontline clinicians experienced more frequent workplace violence (WPV) than the COVID-19 treating frontline clinicians (χ2 = 7.6, p = 0.006). COVID-19 treating frontline clinicians reported higher QOL compared to their non-COVID-19 treating frontline counterparts (b = 0.3, p = 0.042), after adjusting for WPV experience. COVID-19 treating and non- COVID-19 treating frontline clinicians reported similar PHQ-9, GAD-7, and ISI total scores (all p values > 0.05). CONCLUSION: This study did not reveal more severe post-COVID-19 mental health symptoms in COVID-19 treating frontline clinicians compared to non-COVID-19 treating frontline clinicians. It is possible that the implementation of timely and appropriate mental health, social and financial supports could have prevented the worsening of mental health symptoms among the COVID-19 treating frontline clinicians after the first COVID-19 outbreak in China.

Network Analysis of Comorbid Anxiety and Insomnia Among Clinicians with Depressive Symptoms During the Late Stage of the COVID-19 Pandemic: A Cross-Sectional Study.

Background: A high proportion of clinicians experienced common anxiety, insomnia and depression during the COVID-19 pandemic. This study examined the item-level association of comorbid anxiety and insomnia symptoms among clinicians who suffered from depressive symptoms during the late stage of the COVID-19 pandemic using network analysis (NA). Methods: Clinicians with depressive symptoms (with a Patients Health Questionnaire (PHQ-9) total score of 5 and above) were included in this study. Anxiety and insomnia symptoms were measured using the Generalized Anxiety Disorder Scale - 7-item (GAD-7) and Insomnia Severity Index (ISI), respectively. Network analysis was conducted to investigate the network structure, central symptoms, bridge symptoms, and network stability of these disturbances. Expected influence (EI) was used to measure the centrality of index. Results: Altogether, 1729 clinicians were included in this study. The mean age was 37.1 [standard deviation (SD)=8.04 years], while the mean PHQ-9 total score was 8.42 (SD=3.33), mean GAD-7 total score was 6.45 (SD=3.13) and mean ISI total score was 8.23 (SD=5.26). Of these clinicians, the prevalence of comorbid anxiety symptoms (GAD-7≥5) was 76.8% (95% CI 74.82-78.80%), while the prevalence of comorbid insomnia symptoms (ISI≥8) was 43.8% (95% CI: 41.50-46.18%). NA revealed that nodes ISI7 ("Interference with daytime functioning") (EI=1.18), ISI4 ("Sleep dissatisfaction") (EI=1.08) and ISI5 ("Noticeability of sleep problem by others") (EI=1.07) were the most central (influential) symptoms in the network model of comorbid anxiety and insomnia symptoms in clinicians. Bridge symptoms included nodes PHQ3 ("Sleep") (bridge EI=0.55) and PHQ4 ("Fatigue") (bridge EI=0.49). Gender did not significantly influence the network structure, but "having the experience of caring for COVID-19 patients" significantly influenced the network structure. Conclusion: Central symptoms and key bridge symptoms identified in this NA should be targeted in the treatment and preventive measures for clinicians suffering from comorbid anxiety, insomnia and depressive symptoms during the late stage of the COVID-19 pandemic.

Prognostic value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in laryngeal cancer: What should we expect from a meta-analysis?

Background: Although many studies have shown the predictive value of the high neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for various cancers, there are conflicting reports regarding their role in laryngeal cancer. This study aimed to evaluate the relationship between high NLR/PLR and laryngeal cancer prognosis with the help of meta-analysis. Methods: PubMed, Embase and other databases were used to search relevant studies. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated using either the random-effect-model or fixed-effect model. Sensitivity analyses and subgroups were used to explore potential sources of heterogeneity. Publication bias was also adopted. Result: 5716 patients from 20 studies were involved in this meta-analysis. Pooled observed survival (OS) (HR=1.70, 95%CI, 1.41-2.04, p<0.001), progression-free survival (PFS) (HR=1.81, 95%CI, 1.47-2.23, p<0.001), and disease-free survival (DFS) (HR=1.86, 95%CI, 1.45-2.38, p<0.001) showed the prediction of high NLR for poor prognosis. It also suggested that high PLR predicted poor OS (HR=1.89, 95%CI, 1.21-2.94, p<0.001). Conclusion: This study indicated that high NLR was associated with poor OS, PFS, and DFS in laryngeal cancer patients, and high PLR was related to poor OS. Both could be potential predictors of prognosis.

Network analysis of comorbid depression and anxiety and their associations with quality of life among clinicians in public hospitals during the late stage of the COVID-19 pandemic in China.

BACKGROUND: Mental health problems are common among clinicians working in public hospitals even in the late stage of the COVID-19 pandemic. Network analysis is a novel approach to explore interactions between mental health problems at the symptom level. This study examined the network structure of comorbid depression and anxiety and their associations with quality of life (QOL) among hospital clinicians in China during the late stage of the COVID-19 pandemic. METHODS: A total of 4931 participants were recruited from October 13 to 22, 2020. The nine-item Patient Health Questionnaire (PHQ-9), seven-item Generalized Anxiety Disorder Scale (GAD-7), and the World Health Organization Quality of Life Questionnaire-Brief Version (WHOQOL-BREF) were used to measure depressive and anxiety symptoms, and QOL, respectively. Central and bridge symptoms were identified with centrality and bridge centrality indices, respectively. Network stability was examined using the case-dropping procedure. RESULTS: The prevalence of depression (defined as PHQ-9 total score ≥ 5) was 35.1 % [95 % confidence interval (CI) = 33.73-36.41 %)], the prevalence of anxiety (GAD-7 total score ≥ 5) was 32.5 % (95 % CI = 31.20-33.84 %), while the prevalence of comorbid depression and anxiety was 26.9 % (95 % CI = 25.7-28.2 %). "Impaired motor skills", "Trouble relaxing" and "Uncontrollable worry" were the central symptoms in the whole depression-anxiety network. "Irritability", "Feeling afraid" and "Sad mood" were the most key bridge symptoms linking depression and anxiety. Three symptoms ("Fatigue", "Trouble relaxing" and "Nervousness") were the most strongly and negatively associated with QOL. Neither gender nor the experiences of caring for COVID-19 patients was associated with network global strength, distribution of edge weights or individual edge weights. LIMITATIONS: The causality between variables could not be established. Depressive and anxiety symptoms were assessed by self-report measures, which may result in recall bias and limitations in capturing clinical phenomena. CONCLUSIONS: Both the central (i.e., "Impaired motor skills", "Trouble relaxing" and "Uncontrollable worry") and bridge symptoms (i.e., "Irritability", "Feeling afraid" and "Sad mood") identified in this network analysis should be targeted in specific treatment and preventive measures for comorbid depressive and anxiety symptoms among clinicians in the late stage of the pandemic. Furthermore, "Fatigue", "Trouble relaxing" and "Nervousness" are key symptoms to address to improve clinicians' QOL.

Burnout and well-being of healthcare workers in the post-pandemic period of COVID-19: a perspective from the job demands-resources model.

BACKGROUND: The present study aimed 1) to examine the effects of epidemic-related job stressors, perceived social support and organizational support on the burnout and well-being of Chinese healthcare workers in the period of COVID-19 regular epidemic prevention and control and 2) to investigate the moderating effects of social support and organizational support on the relationship between job stressors and burnout and well-being within the theoretical framework of the Job Demands-Resources (JD-R) model. METHODS: A sample of healthcare workers (N = 3477) from 22 hospitals in Beijing, China participated in the cross-sectional investigation in October 2020 and reported epidemic-related job stressors, perceived social support, organizational support, burnout, anxiety and depression symptoms. RESULTS: 1) Medical doctors, females, people aged from 30 to 50, and those who worked in the second line during the pandemic reported higher scores of psychological symptoms and burnout in the period of regular epidemic prevention and control; 2) Epidemic-related job stressors positively predicted burnout, anxiety, and depression among healthcare workers; 3) Perceived social support and organizational support were negatively related to reported burnout, anxiety and depression symptoms; 4) Social support reduced the adverse effects of epidemic-related job stressors on anxiety and depression but enhanced the association between stressors and burnout; 5) Organizational support mitigated the adverse effects of epidemic-related job stressors on depression. CONCLUSION: The results shed light on preventing burnout and enhancing the psychological well-being of healthcare workers under epidemic prevention and control measures by reducing epidemic-related job stressors and strengthening personal and organizational support systems.

The role of ICOS in allergic disease: Positive or Negative?

With the rapid increase in the incidence of allergic diseases, the mechanisms underlying the development of these diseases have received a great deal of attention, and this is particularly true in regard to the role of ICOS in allergic diseases. Current studies have revealed that ICOS affects the functional activity of multiple immune cells that modulate the adaptive immune system. Additionally, ICOS also plays a crucial role in mediating cellular immunity and coordinating the response of the entire immune system, and thus, it plays a role in allergic reactions. However, the ICOS/ICOS-ligand (ICOS-L) axis functions in a dual role during the development of multiple allergic diseases. In this review, we explore the role of ICOS/ICOSL in the context of different immune cells that function in allergic diseases, and we summarize recent advances in their contribution to these diseases.

Investigation of lower limb injury under different contact stiffness for drivers during frontal crash.

Lower extremity injuries in AIS2+ were the most costly injuries through the statistic analysis of traffic accidents. This study aimed to investigate the response characteristics of the lower limb with different contact stiffness, in which knee cushion and foot cushion were applied. First, a model with a human body and a car was established, and the muscle function was activated in lower extremity of human model. Second, the deceleration pulse with a peak of 186 m/s2 was applied to the car to simulate the frontal crash. Then, four sets of simulations with different contact stiffness are conducted to obtain the lower limb responses. Results indicate that the maximum loading of the left and right legs during the impact wes 1.29 and 1.22 kN, respectively. Meanwhile, the maximum moment were 28.82 and 52.17 Nm, respectively. The maximum stress of lower extremity was 87.35 MPa, and the maximum tibia index was 0.230. It was demonstrated that the injury risk of the femur in the groups with equipment of knee cushion and foot cushion was low, but the injury risk of the tibia increased at the same time. This study could provide a reference to the study of lower limb injury in a frontal impact.

The MATRICS Consensus Cognitive Battery: Psychometric Properties of the Chinese Version in Young Patients With Major Depression Disorder.

Background: Young patients with major depressive disorder are also associated with cognitive deficits. The development of an accurate and effective battery to measure cognitive impairment in young patients with major depressive disorder (Y-MDD) is necessary for both research and clinical practice. This study was designed to test the psychometric properties of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) in Y-MDD. Method: Fifty Y-MDD patients, 38 euthymic young patients with bipolar disorder (Y-BD), and 51 healthy teenagers were recruited. The MCCB and the Montreal Cognitive Assessment (MoCA) were administered to assess cognitive impairment at baseline. The MCCB was also assessed 2 weeks later in Y-MDD patients. All subjects were between the ages of 13 and 24 years. Result: In the current study, cognitive impairment was greater in Y-BD patients than in Y-MDD patients in some domains. The MCCB has good internal consistency and reliability in Y-MDD patients. The Pearson correlation coefficients for retest reliability were good. Our findings also revealed an acceptable correlation between the MCCB and the MoCA, indicating good concurrent validity of the MCCB. Furthermore, exploratory factor analysis of the MCCB in Y-MDD patients revealed five domains with acceptable internal structures. Conclusion: The MCCB has acceptable psychometric properties and is a sensitive battery of cognitive impairment in Y-MDD patients. In the future, additional studies need to be carried out with larger samples while controlling for the use of psychotropic medications and antidepressants to validate the findings of the present study.

The comprehensive measurement method of energy conservation and emission reduction in the whole process of urban sewage treatment based on carbon emission.

It is of great significance to establish a carbon emission management system and carbon emission reduction target to put forward emission reduction measures for each subunit of a sewage treatment plant. In this paper, a mathematical model was constructed for calculating carbon emission in the whole sewage treatment system process. Meanwhile, the model calculated the carbon emission changes after upgrading three sewage treatment plants and identified the critical controlling unit. The results showed that the CO2 produced from electric energy consumption and chemical application was the primary source of carbon emission of wastewater treatment. Raising sewage discharge standards appropriately could effectively reduce the carbon emission generated by each link of the wastewater treatment plant. Further improvement of effluent standards could adversely affect sewage treatment plants in terms of energy, resources, and greenhouse gas emissions. In addition, raising the standard of total phosphorus concentration in the effluent may lead to a corresponding increase in the amount of phosphorus removal agents, as well as an increase in indirect carbon emission, material consumption, and chemical sludge. Therefore, it is necessary to develop sewage treatment technologies that are economical, applicable, energy-saving, and environmental friendly to realize the environmental benefits of carbon emission reduction in sewage treatment and sustainable utilization of energy and resource from wastewater.

Whole-transcriptome sequencing reveals heightened inflammation and defective host defence responses in chronic rhinosinusitis with nasal polyps.

INTRODUCTION: The pathways underlying chronic rhinosinusitis with nasal polyps (CRSwNP) are unclear. We conducted genome-wide gene expression analysis to determine pathways and candidate gene sets associated with CRSwNP. METHODS: We performed whole-transcriptome RNA sequencing on 42 polyp (CRSwNP-NP) and 33 paired nonpolyp inferior turbinate (CRSwNP-IT) tissues from patients with CRSwNP and 28 inferior turbinate samples from non-CRS controls (CS-IT). We analysed the differentially expressed genes (DEGs) and the gene sets that were enriched in functional pathways. RESULTS: Principal component-informed analysis revealed cilium function and immune regulation as the two main Gene Ontology (GO) categories differentiating CRSwNP patients from controls. We detected 6182 and 1592 DEGs between CRSwNP-NP versus CS-IT and between CRSwNP-NP versus CRSwNP-IT tissues, respectively. Atopy status did not have a major impact on gene expression in various tissues. GO analysis on these DEGs implicated extracellular matrix (ECM) disassembly, O-glycan processing, angiogenesis and host viral response in CRSwNP pathogenesis. Ingenuity Pathway Analysis identified significant enrichment of type 1 interferon signalling and axonal guidance canonical pathways, angiogenesis, and collagen and fibrotic changes in CRSwNP (CRSwNP-NP and CRSwNP-IT) tissues compared with CS-IT. Finally, gene set enrichment analysis implicated sets of genes co-regulated in processes associated with inflammatory response and aberrant cell differentiation in polyp formation. CONCLUSIONS: Gene signatures involved in defective host defences (including cilia dysfunction and immune dysregulation), inflammation and abnormal metabolism of ECM are implicated in CRSwNP. Functional validation of these gene expression patterns will open opportunities for CRSwNP therapeutic interventions such as biologics and immunomodulators.

Home environment and diseases in early life are associated with allergic rhinitis.

OBJECTIVE: Risk factors in relation to allergic rhinitis (AR) remain unclear despite considerable interest. This study aimed to analysis the relationship between home environment and diseases in early life and AR. METHODS: In a case-control survey, 242 AR patients and 258 healthy persons responded to questionnaires designed to capture pre-pregnancy/pregnancy diseases, maternal medication usage, diseases in early life of participants, family allergic history and home environmental factors. Forty risk factors potentially connected with AR were investigated and analyzed with chi-square test and logistic regression. RESULTS: There was no correlation between mother's disorders such as periodontitis, chronic rhinitis, diabetes etc. and AR (p > 0.05). A logistic regression analysis showed that neonatal jaundice (p < 0.001), respiratory system infection (p < 0.001), diarrhea (p < 0.01), eczema (p < 0.01) in the early life and home environmental factors such as house decoration (p < 0.01), mold environment (p < 0.001), keeping flowers and plants (p < 0.001), passive smoking (p < 0.01) were associated with AR. CONCLUSION: Diseases in early life and home environment are closely associated with AR.

Aberrant localization of FOXJ1 correlates with the disease severity and comorbidities in patients with nasal polyps.

BACKGROUND: Upper airway inflammatory diseases are associated with abnormal expression of nasal epithelial forkhead-box J1 (FOXJ1) which regulates motile cilia formation. We sought to investigate whether aberrant FOXJ1 localizations correlate with the disease severity and the co-existence of allergic rhinitis (AR) or asthma in patients with nasal polyps (NPs). METHODS: We elucidated localization patterns of FOXJ1 by performing immunofluorescence assays in nasal specimens and cytospin samples from controls and patients with NPs. We also assayed mRNA expression levels of FOXJ1 by using quantitative real-time polymerase chain reaction. Four localization patterns [normal (N), intermediate (I), mislocalization (M), and absence (A)] were defined. A semi-quantitative scoring system was applied for demonstrating FOXJ1 localization in five areas per paraffin section, with individual sections being scored between 0 and 2. RESULTS: FOXJ1 localization score was significantly higher in samples from NPs than in controls (P < 0.001). Elevated FOXJ1 localization scores and down-regulation of FOXJ1 mRNA levels were observed in NPs with co-existing AR or asthma (all P < 0.05). Moreover, FOXJ1 localization scores positively correlated with Lund-Mackay score (r = 0.362, P = 0.007). Of primary cytospin samples, the mean percentage of patients with FOXJ1 localization patterns N, I, M and A was 15.0%, 3.3%, 53.3% and 28.3% in NPs, and 82.5%, 5.0%, 5.0% and 7.5% in controls, respectively (P < 0.001). CONCLUSIONS: Aberrant localization of FOXJ1 correlates with the severity and co-existence of AR or asthma in patients with NPs, and might be a novel target for assessment and intervention in NPs.

H3N2 influenza virus infection enhances oncostatin M expression in human nasal epithelium.

Tight junctions (TJs) alteration is commonly seen in airway inflammatory diseases. Oncostatin M (OSM) is an inflammatory mediator associated with chronic rhinosinusitis with nasal polyps (CRSwNP). We have previously shown that human nasal epithelial cells (hNECs) are highly permissive cells for influenza A virus (IAV). However, its role in TJs alteration and the effects of IAV on inducing OSM expression in nasal epithelium remains to be further investigated. In this study, OSM and TJs expression was measured and compared between inferior turbinate from healthy controls and nasal polyps from CRSwNP. Additionally, hNECs cultured at air-liquid interface (ALI) were infected with H3N2 influenza virus to study the role of influenza virus in inducing epithelial OSM expression as a possible means of exacerbation. The expression of ZO-1, claudin-1, and occludin was markedly decreased and correlated negatively with that of OSM in CRSwNP. By using the in vitro hNEC model, H3N2 infection resulted in significantly increased OSM expression (2.2-, 4.7- and 3.9-fold higher at 8, 24, and 48 h post-infection vs. mock infection). Furthermore, OSM is found to co-localize with ciliated and goblet cells in hNECs infected with H3N2 influenza virus. Our findings demonstrated that increased OSM expression is implicated in CRSwNP as a possible mechanism of TJs' impairment, which can be further augmented following influenza infection via epithelial OSM expression, possibly contributing to exacerbations.