Pulmonary function, genetic predisposition, and the risk of cirrhosis: A prospective cohort study.

OBJECTIVE: Pulmonary function is associated with the development of chronic liver disease. However, evidence of the association between pulmonary function and cirrhosis risk is still lacking. This study aimed to investigate the longitudinal associations of pulmonary function with the development of cirrhosis, and to explore whether genetic predisposition to cirrhosis could modify these associations. METHODS: Of 294,835 participants free of cirrhosis and had undergone spirometry at baseline from the UK Biobank were included. Cirrhosis diagnoses were ascertained through linked hospital records and death registries. Cox proportional hazard models were employed to investigate the longitudinal associations between pulmonary function, genetic predisposition, and cirrhosis risk. RESULTS: During a median follow-up of 12.0 years, 2598 incident cirrhosis cases were documented. Compared to individuals with normal spirometry findings, those with preserved ratio impaired spirometry (PRISm) findings (hazard ratio [HR] and 95% confidence interval [CI]: 1.32 [1.18, 1.48]) and airflow obstruction (HR [95%CI]: 1.19 [1.07, 1.31]) had a higher risk of developing cirrhosis after adjustments. These associations were consistent across all categories of genetic predisposition, with no observed modifying effect of genetic predisposition. In joint exposure analyses, the highest risk was observed in individuals with both a high genetic predisposition for cirrhosis and PRISm findings (HR [95% CI]: 1.74 [1.45, 2.08]). CONCLUSIONS: Our findings indicate that worse pulmonary function is a significant risk factor of cirrhosis, irrespective of genetic predisposition. Early identification and appropriate intervention for pulmonary function may lead to more effective healthcare resource utilization and reduce the burden associated with cirrhosis.

Associations between household solid fuel use and hearing loss in a Chinese population: A population-based prospective cohort study.

Hearing loss, a common chronic condition, severely affects the quality of human life. However, the longitudinal relationships between household solid fuel use and hearing loss are unclear. To explore the associations between household solid fuel use and hearing loss in a Chinese population. There were 8835 participants enrolled in this prospective cohort study. Hearing function was assessed by asking the following self-reported question. Cox proportional hazards regression models were used to examine the relationships between baseline household solid fuel use and hearing loss incidence. After 6 (range, 2-7) years of follow-up, 1654 (18.72%) of 8835 participants developed hearing loss. This study demonstrated that increasing baseline solid fuel exposure was associated with a higher rate of poor hearing function (P for trend < 0.01). Compared with the clean fuel group (both cooking and heating), the hazard ratios (HR) (95% confidence intervals) of poor hearing function for the solid fuel group (cooking or heating) and both solid fuel groups (both cooking and heating) were 1.17 (1.01, 1.37) and 1.26 (1.09, 1.45) after adjustments, respectively. In subgroup analysis of household energy sources, the use of solid fuels for both heating (HR, 1.21; 1.07, 1.37) and cooking (HR, 1.12; 1.01, 1.26) was related to a higher incidence of poor hearing function. In subgroup analysis of place of residence, more solid fuel use was associated with a higher rate of poor hearing function in urban communities (HR, 1.39; 1.12, 1.74) but not in rural villages (HR, 1.18; 0.97, 1.45). Moreover, compared with the population that used solid fuel for cooking at both baseline and follow-up, those who switched from solid to clean fuel had a lower risk of developing poor hearing function (HR, 0.54, 0.46-0.63). This study demonstrates that household solid fuel use is closely associated with poor hearing function. Programs that educate individuals on the effects of household fuel use on hearing function should be established, especially in urban communities.

The Role of Epigenetics in the Chronic Sinusitis with Nasal Polyp.

PURPOSE OF REVIEW: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and heterogeneous inflammatory disease. The underlying epigenetic mechanisms and treatment of CRSwNP are partially understood. Of the different epigenetic changes in CRSwNP, histone deacetylases (HDACs), methylation of DNA, and the levels of miRNA are widely studied. Here, we review the human studies of epigenetic mechanisms in CRSwNP. RECENT FINDINGS: The promoters of COL18A1, PTGES, PLAT, and TSLP genes are hypermethylated in CRSwNP compared with those of controls, while the promoters of PGDS, ALOX5AP, LTB4R, IL-8, and FZD5 genes are hypomethylated in CRSwNP. Promoter hypermethylation suppresses the gene expression, while promoter hypomethylation increases the gene expression. Studies have shown the elevation in the levels of HDAC2, HDAC4, and H3K4me3 in CRSwNP. In CRSwNP patients, there is also an upregulation of certain miRNAs including miR-125b, miR-155, miR-19a, miR-142-3p, and miR-21 and downregulation of miR-4492. Epigenetics takes part in the immunology of CRSwNP and may give rise to endotypes of CRSwNP. Both HDAC2 and the miRNA including miR-18a, miR-124a, and miR-142-3p may take function in the regulation of glucocorticoid resistance. HDAC inhibitors and KDM2B have shown effectiveness in decreasing nasal polyp, and DNA methyltransferase (DNMT) or HDAC inhibitors may have a potential efficacy for the treatment of CRSwNP. Recent advances in the epigenetics of CRSwNP have led to the identification of several potential therapeutic targets for this disease. The use of epigenetics may provide novel and effective biomarkers and therapies for the treatment of nasal polyp.

Navigation-Assisted Treatment of Giant Cysts in the Pterygopalatine Fossa With Endoscopy Method.

A couple of cysts lying in the pterygopalatine fossa are rare. The authors report a case of a 28-year-old woman who was admitted to the authors' hospital with a 1-month history of headache and numbness on the left head. Three-dimensional computed tomography revealed a large soft mass in the pterygopalatine fossa. Magnetic resonance imaging showed that there were a couple of cysts in the pterygopalatine fossa. One cyst measured 41 × 38 × 34 mm and the other 23 × 19 × 19 mm. A transpterygoid transnasal endoscopic approach and resection of the lesion was performed. The authors opened the cyst with coblation and the lesion showed a lot of transparent thick yellow liquid. The authors located the posterior wall the other cyst with ENT image navigation. The puncture was conducted and a lot of yellow liquid flowed out of the lesion. The patient recovered rapidly. The headache and numbness were alleviated and disappeared after 1 month. The patient currently has no evidence of recurrence at 1 year postoperatively. The coblation and ENT image navigation make the surgeon more easily to achieve risk-free surgery under endoscopy.

Overexpressed FKBP5 mediates colorectal cancer progression and sensitivity to FK506 treatment via the NF-κB signaling pathway.

Colorectal cancer (CRC) is a common and deadly tumor. FK506-binding protein 5 (FKBP5) is associated with some cancers, but the role of FKBP5 in CRC is not clear. The present study aimed to reveal the relationship between FKBP5 and CRC and to uncover the roles of FK506 in CRC. In total, 96 CRC patients were recruited. Survival analysis was conducted using the Kaplan-Meier method and COX regression analyses. Bioinformatics analyses were performed to explore the functions of FKBP5. The mechanisms of FKBP5 and the roles of FK506 in CRC progression were clarified by immunohistochemistry, MTS, scratch assay, transwell and flow cytometric analyses via in vitro and in vivo experiments. FKBP5 was overexpressed in 77 cancer tissues compared to that in matched normal tissues, and the overall survival rate of these patients was relatively shorter. Bioinformatics analyses showed that FKBP5 regulates proliferation, invasion, migration, epithelial-mesenchymal transition and nuclear factor-kappa B (NF-κB) signaling. The upregulation or downregulation of FKBP5 dramatically increases or decreases the proliferation, invasion and migration abilities of CRC cells. The expression of NF-κB, inhibitor B kinase α, matrix metalloproteinase-2 and metalloproteinase-9 positively correlated with FKBP5. FK506 inhibits the progression of CRC via the FKBP5/NF-κB signaling pathway. Our study identified a regulatory role for FKBP5 in CRC progression. Therefore, targeting FKBP5 may provide a novel treatment approach for CRC. FK506 can inhibit the progression of CRC by restraining the FKBP5/NF-κB signaling pathway and is expected to become a new drug for the treatment of CRC.

Association between dietary patterns and chronic kidney disease combined with hyperuricemia.

Background and aims: Chronic kidney disease (CKD) combined with hyperuricemia is a concerning health issue, but the association between this condition and dietary patterns remains poorly understood. The aim of this study was to assess the associations between dietary patterns and CKD combined with hyperuricemia. Methods: This cross-sectional study was conducted involving 12 318 participants aged 18-79 years during 2018-2020. Dietary intake information was collected using a validated 110-item food frequency questionnaire. Factor analysis was used to identify major dietary patterns. CKD was defined as the presence of albuminuria or an estimated glomerular filtration rate <60 mL min-1 1.73 m-2. Hyperuricemia was defined as serum uric acid levels >420 µmol L-1 both in men and women. Logistic regression models were applied to assess the association between dietary patterns and the risk of CKD combined with hyperuricemia. Results: Five major dietary patterns were identified: 'healthy pattern', 'traditional pattern', 'animal foods pattern', 'sweet foods pattern', and 'tea-alcohol pattern', which together explained 38.93% of the variance in the diet. After adjusting for potential confounders, participants in the highest quartile of the traditional pattern had a lower risk of CKD combined with hyperuricemia (OR = 0.49, 95% CI: 0.32-0.74, Pfor trend < 0.01). Conversely, participants in the highest quartile of the sweet foods pattern had a higher risk compared to those in the lowest quartile (OR = 1.69, 95% CI: 1.18-2.42, Pfor trend < 0.01). However, no significant association was observed between the healthy pattern, animal foods pattern and tea-alcohol pattern and the risk of CKD combined with hyperuricemia. Conclusions: Our results suggest that the traditional pattern is associated with a reduced risk of CKD combined with hyperuricemia, whereas the sweet foods pattern is associated with an increased risk.

EP300 restores the glycolytic activity and anti-tumor function of CD8+ cytotoxic T cells in nasopharyngeal carcinoma.

Competition for glucose may metabolically limit T cells during cancer progression. This study shows that culturing in the condition medium (CM) of NPC c6661 cells restricted glycolytic and immune activities of CD8+ T cells. These cells also exhibited limited tumor-eliminating effects in mouse xenograft tumor models. Glucose supplementation restored glycolysis and immune activity of CD8+ T cells in vitro and in vivo by rescuing the expression of E1A binding protein p300 (EP300). EP300 upregulated bromodomain PHD finger transcription factor (BPTF) expression by catalyzing H3K27ac modification, and BPTF further activated AT-rich interaction domain 1A (ARID1A) transcription. Either BPTF or ARID1A knockdown in CD8+ T cells reduced their glycolytic activity, decreased the secretion of cytotoxic molecules, and blocked the tumor-killing function in mice. Overall, this study demonstrates that EP300 restores the glycolytic and anti-tumor activities of CD8+ T cells in the glucose restriction condition in NPC through the BPTF/ARID1A axis.

Cyp2e1 protects against OVA-induced allergic rhinitis through the inhibition of Th2 cell activation and differentiation: Mediated by MAFB.

Allergic rhinitis (AR) is a common allergic disease. Cytochrome P450, family 2, subfamily e, polypeptide 1 (Cyp2e1) is a member of the cytochrome P450 family of enzymes, while its role in AR is still unveiled. In AR mice, T cell-specific overexpression of Cyp2e1 relieved the AR symptoms. Overexpressed-Cyp2e1 restrained the infiltration of eosinophils and mast cells in the nasal mucosa of mice, and the inflammatory cells in nasal lavage fluid (NALF). Cyp2e1 overexpressed mice exhibited decreased goblet cell hyperplasia and mucus secretion as well as decreased MUC5AC expression in nasal mucosa. The epithelial permeability and integrity of nasal mucosa were improved upon Cyp2e1 overexpression in AR mice, as evidenced by decreased fluorescein isothiocyanate-dextran 4 content in serum, increased expression of IL-25, IL-33, and TSLP in NALF, and increased expression of ZO-1 and occluding in nasal mucosa. Cyp2e1 inhibited Th2 immune response by decreasing the expression and secretion of IL-4, IL-5, and IL-13 as well as the expression of GATA-3 in NALF or nasal mucosa. We proved that Cyp2e1 inhibited the differentiation of naïve CD4+ T cells toward the Th2 subtype, which was regulated by MAFB by binding to Cyp2e1 promoter to activate its transcription. Overall, these results show the potential role of Cyp2e1 in alleviating AR symptoms by restraining CD4+ T cells to Th2 cell differentiation. Our findings provide further insight into the AR mechanism.

Knockdown of Cadherin 26 Prevents the Inflammatory Responses of Allergic Rhinitis.

OBJECTIVES: Allergic rhinitis (AR) is an inflammatory autoimmune disease with disorder of the nasal mucosa. Cadherin 26 (CDH26), an alpha integrin-binding epithelial receptor, is regulated during allergic inflammation. This study aimed to investigate whether CDH26 contributes to the severity of AR. STUDY DESIGN: In vivo and in vitro. METHODS: We investigated the effects of CDH26 knockdown by lentivirus (LV)-mediated shRNA on ovalbumin (OVA)-induced AR mice and IL-13-stimulated human nasal epithelial cells (NECs). RESULTS: CDH26 mRNA and protein expression was significantly increased in the nasal mucosa of AR patients and mice. Intranasal instillation of LV-shCDH26 alleviated allergic symptoms and decreased the histological changes of nasal mucosa in AR mice. Furthermore, the serum levels of OVA-specific IgE, IgG, pro-inflammatory factors IL-25, IL-33, and TSLP were decreased in AR mice with CDH26 knockdown. With regard to AR-induced Th2 inflammation, LV-shCDH26 intervention effectively decreased the distribution of CD4+ /GATA3+ Th2 cells, and the mRNA expression of IL-4, IL-5, and IL-13 in the nasal mucosa. CDH26 knockdown down-regulated the expression of ß-catenin but not for E-cadherin and ZO-1 in nasal mucosa induced by AR. In vitro, CDH26 knockdown inhibited the protein expression of TSLP, GM-CSF and eotaxin in NECs, and CDH26 overexpression remarkably promoted the production of these inflammatory factors in IL-13-induced NECs. CONCLUSIONS: CDH26 knockdown attenuates the AR-induced inflammatory response both in vivo and in vitro. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1558-1567, 2023.

Intercellular mitochondrial transfer in the brain, a new perspective for targeted treatment of central nervous system diseases.

AIM: Mitochondria is one of the important organelles involved in cell energy metabolism and regulation and also play a key regulatory role in abnormal cell processes such as cell stress, cell damage, and cell canceration. Recent studies have shown that mitochondria can be transferred between cells in different ways and participate in the occurrence and development of many central nervous system diseases. We aim to review the mechanism of mitochondrial transfer in the progress of central nervous system diseases and the possibility of targeted therapy. METHODS: The PubMed databank, the China National Knowledge Infrastructure databank, and Wanfang Data were searched to identify the experiments of intracellular mitochondrial transferrin central nervous system. The focus is on the donors, receptors, transfer pathways, and targeted drugs of mitochondrial transfer. RESULTS: In the central nervous system, neurons, glial cells, immune cells, and tumor cells can transfer mitochondria to each other. Meanwhile, there are many types of mitochondrial transfer, including tunneling nanotubes, extracellular vesicles, receptor cell endocytosis, gap junction channels, and intercellular contact. A variety of stress signals, such as the release of damaged mitochondria, mitochondrial DNA, or other mitochondrial products and the elevation of reactive oxygen species, can trigger the transfer of mitochondria from donor cells to recipient cells. Concurrently, a variety of molecular pathways and related inhibitors can affect mitochondrial intercellular transfer. CONCLUSION: This study reviews the phenomenon of intercellular mitochondrial transfer in the central nervous system and summarizes the corresponding transfer pathways. Finally, we propose targeted pathways and treatment methods that may be used to regulate mitochondrial transfer for the treatment of related diseases.

The driving mechanism and targeting value of mimicry between vascular endothelial cells and tumor cells in tumor progression.

The difficulty and poor prognosis of malignant tumor have always been a difficult problem to be solved. The internal components of solid tumor are complex, including tumor cells, stromal cells and immune cells, which play an important role in tumor proliferation, migration, metastasis and drug resistance. Hence, targeting of only the tumor cells will not likely improve survival. Various studies have reported that tumor cells and endothelial cells have high plasticity, which is reflected in the fact that they can simulate each other's characteristics by endothelial-mesenchymal transition (EndMT) and vasculogenic mimicry (VM). In this paper, this mutual mimicry concept was integrated and reviewed for the first time, and their similarities and implications for tumor development are discussed. At the same time, possible therapeutic methods are proposed to provide new directions and ideas for clinical targeted therapy and immunotherapy of tumor.

Household polluting cooking fuels and adverse birth outcomes: An updated systematic review and meta-analysis.

Background and aim: The current study aimed to clarify the association between household polluting cooking fuels and adverse birth outcomes using previously published articles. Methods: In this systematic review and meta-analysis, a systematic literature search in PubMed, Embase, Web of Science, and Scopus databases were undertaken for relevant studies that had been published from inception to 16 January 2023. We calculated the overall odds ratio (OR) and 95% confidence interval (CI) for adverse birth outcomes [low birth weight (LBW), small for gestational age (SGA), stillbirth, and preterm birth (PTB)] associated with polluting cooking fuels (biomass, coal, and kerosene). Subgroup analysis and meta-regression were also conducted. Results: We included 16 cross-sectional, five case-control, and 11 cohort studies in the review. Polluting cooking fuels were found to be associated with LBW (OR: 1.37, 95% CI: 1.24, 1.52), SGA (OR: 1.48, 95% CI: 1.13, 1.94), stillbirth (OR: 1.38, 95% CI: 1.23, 1.55), and PTB (OR: 1.27, 95% CI: 1.19, 1.36). The results of most of the subgroup analyses were consistent with the main results. In the meta-regression of LBW, study design (cohort study: P < 0.01; cross-sectional study: P < 0.01) and sample size (≥ 1000: P < 0.01) were the covariates associated with heterogeneity. Cooking fuel types (mixed fuel: P < 0.05) were the potentially heterogeneous source in the SGA analysis. Conclusion: The use of household polluting cooking fuels could be associated with LBW, SGA, stillbirth, and PTB. The limited literature, observational study design, exposure and outcome assessment, and residual confounding suggest that further strong epidemiological evidence with improved and standardized data was required to assess health risks from particular fuels and technologies utilized.

MAF bZIP Transcription Factor B (MAFB) Protected Against Ovalbumin-Induced Allergic Rhinitis via the Alleviation of Inflammation by Restoring the T Helper (Th) 1/Th2/Th17 Imbalance and Epithelial Barrier Dysfunction.

PURPOSE: This work aimed to investigate the effects of MAF bZIP transcription factor B (MAFB) on the progression of allergic rhinitis (AR). PATIENTS AND METHODS: Nasal mucosa was isolated from AR patients and healthy individuals from Shengjing Hospital of China Medical University. The experimental procedures were approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University (2019PS341K) in accordance with the Declaration of Helsinki. Informed consents were signed by participants or a parent/legal guardian of the participants under 18 years old of age. Then, an AR mouse model with MAFB overexpression was established with 25 µg ovalbumin (OVA) sensitization on day 0, 7, 14, followed by an injection with 1×107 TU/mL lentivirus MAFB on day 19 and a nasal challenge with 500 µg OVA from day 21 to 27. RESULTS: The results revealed that MAFB was down-regulated in the nasal mucosa of AR patients. The up-regulation of MAFB protected the AR mice against the OVA-induced allergic symptoms (sneezing and nasal rubbing) by alleviating the OVA-induced epithelial thicknesses, goblet cell hyperplasia, and inflammation including the eosinophil and mast cell infiltration. Moreover, MAFB facilitated the T helper (Th) 1 response and inhibited the Th2 and Th17 responses by the down-regulation of T-box transcription factor 21 and the up-regulation of GATA binding protein-3 as well as retinoid-related orphan receptor-γt in the splenocytes of AR mice. MAFB was found to repress the differentiation of naive CD4+ T cells into Th2 cells. Subsequently, MAFB overexpression reversed the OVA-induced enhancement of epithelial permeability, downregulation of tight junctions, and upregulation of cadherin-26, indicating the protective role of MAFB on epithelial barrier integrity. CONCLUSION: MAFB protected against OVA-induced AR via the alleviation of inflammation by restoring the Th1/Th2/Th17 imbalance and epithelial barrier dysfunction.

Adverse events of coblation or microdebrider in pediatric adenoidectomy: A retrospective analysis in 468 patients.

Objective: Childhood obstructive sleep apnea hypopnea syndrome (OSAHS) is a common clinical disease that can cause serious complications if not treated in time. Adenoidectomy with or without tonsillectomy is the most important first line surgical treatment of obstructive sleep apnea in children. The aim of this study was to compare the differences between these two surgical procedures for adenoidectomy in terms of operation time, intraoperative blood loss, proportion of patients experiencing postoperative delayed hemorrhage, and incidence of adverse events. Study Design: Retrospective analysis. Methods: We performed a retrospective systematic analysis of patient data using the in-house electronic patient records and considered a 2-year period from 2016 to 2017. In total, 468 patients who underwent adenoidectomy under nasal endoscopy with coblation or microdebrider were identified. Results: The coblation adenoidectomy technique was associated with significantly reduced blood loss and operation time. However, incidence of fever, neck pain, and halitosis were significantly lower in the microdebrider adenoidectomy group (p < .01). The difference in the postoperative primary and secondary hemorrhage between the two groups was not statistically significant (p > .05). Conclusion: Coblation adenoidectomy had a significantly higher incidence of adverse events such as halitosis, neck pain, and fever. Therefore, otorhinolaryngologists should consider the differences in adverse events when selecting use of coblation adenoidectomy for pediatric patients. Level of Evidence: IV.

Association between handgrip strength and metabolic syndrome: A meta-analysis and systematic review.

Background: Although muscle strength has been reported to be associated with metabolic syndrome (MetS), the association is still controversial. Therefore, the purpose of this meta-analysis was to identify the association between handgrip strength (HGS) and MetS. Methods: Original research studies involving HGS and MetS from database inception to 20 May 2022 were selected from PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang databases, and Chinese Biomedical Document Service System. The odds ratios (ORs) with 95% confidence intervals (CIs) of MetS for HGS were calculated using a random-effects model. A dose-response analysis was performed. Subgroup analysis and meta-regression were also conducted. Results: Thirty effect sizes (reported in 19 articles) with a total of 43,396 participants were included in this meta-analysis. All studies were considered to be of moderate-to-good quality. An inverse association between HGS (low vs. high) with MetS was shown (OR: 2.59, 95% CI: 2.06-3.25). Subgroup analyses demonstrated the pooled ORs of relative HGS (HGS/weight), relative HGS (HGS/BMI), and absolute HGS were 2.97 (95% CI: 2.37-3.71), 2.47 (95% CI: 1.08-5.63), and 1.34 (95% CI: 1.06-1.68), respectively. Dose-response analysis revealed a significant linear dose-response relationship between relative HGS (HGS/weight) and MetS in observational studies (0.1 HGS/weight: OR, 0.68; 95% CI: 0.62-0.75). Univariate meta-regression analysis indicated that country status, measuring tools of HGS, components of MetS, and diagnosed criteria of MetS explained 16.7%, 26.2%, 30.1%, and 42.3% of the tau-squared in the meta-regression, respectively. Conclusion: The results of the current meta-analysis indicated that lower HGS is associated with a higher risk of MetS. A linear dose-response association between lower relative HGS (HGS/weight) and increased prevalence of MetS was found. Accordingly, a lower HGS is a significant predictor of MetS. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021276730].

HOXA9 Expression is Associated with Advanced Tumour Stage and Prognosis in Nasopharyngeal Carcinoma.

BACKGROUND: Homeobox A9 (HOXA9), a member of the HOX protein family, plays diverse biological roles in embryonic development and carcinogenesis. The prognostic value of HOXA9 expression in nasopharyngeal carcinoma (NPC) is not well-defined. The present study aimed to analyse NPC tissue HOXA9 expression and determine prognostic significance by investigating the relationship between HOXA9 expression and clinicopathologic features. METHODS: Between January 2010 and December 2014, 252 NPC patients and 30 chronic nasopharyngitis patients (control group) were recruited to participate in the present study. Correlations between HOXA9 expression level and clinicopathologic features (including survival) were analysed. RESULTS: High HOXA9 expression was significantly associated with clinical stage (p < 0.01) and higher T stage (p < 0.01). In univariate analysis, high HOXA9 expression predicted overall survival (OS) (p = 0.011). In multivariate analysis, HOXA9 over-expression independently and significantly predicted poorer PFS (p < 0.01, hazard ratio (HR) = 2.387, 95% CI [0.876, 6.545]) and OS (p < 0.01, HR = 2.486, 95% CI [1.041, 8.926]). CONCLUSION: High HOXA9 expression is an independent prognostic factor associated with advanced tumour stage and poorer survival in NPC patients.

Reference Values and Related Factors for Peak Expiratory Flow in Middle-Aged and Elderly Chinese.

Background: Peak expiratory flow (PEF), as an essential index used for screening and monitoring asthma, chronic obstructive pulmonary disease, and respiratory mortality especially in the elderly, is recommended for low-resource settings in low- and middle-income countries. However, few studies have focused on the reference of PEF in China, especially in middle-aged and elderly people. Thus, this study aimed to determine age- and sex-specific reference values of PEF in the middle-aged and elderly Chinese population. Methods: There were 8,914 participants who were included for risk factor analysis and 5,498 participants included for reference value analysis. The PEF was measured using a peak flow meter in liters per minute. The distributions of standardized PEF terciles stratified by sex and age were reported. Multiple linear regression analysis was used to determine the associations between risk factors and PEF. Results: The PEF was higher in men than women across all age subgroups. The value of PEF decreased with age in both men and women. Height, weight, handgrip strength, and residence in rural were positively associated with PEF. Age and smoking status were negatively associated with PEF significantly in both men and women (P < 0.05). The mean PEF values were 367.10 and 253.00 L/min for men and women, respectively. Meanwhile, the prevalence of low PEF was 3.94 and 3.32% for men and women, respectively. Conclusions: Age- and sex-specific centiles of standardized PEF for the middle-aged and elderly Chinese population were estimated. The reference values for low PEF could provide reference standards for epidemiological studies and clinical practices in the future. Interventions to improve lung functions or to prevent respiratory disease should be paid more attention to factors associated with PEF.

Shikonin-induced necroptosis in nasopharyngeal carcinoma cells via ROS overproduction and upregulation of RIPK1/RIPK3/MLKL expression.

Objective: Shikonin has inhibitory effects against nasopharyngeal carcinoma that are mediated through the apoptotic pathway. However, necroptosis signaling pathways may enable the elimination of apoptosis-resistant cancers when induced with targeted therapeutic agents. Thus, there is a need to clarify whether shikonin can cause necroptosis in nasopharyngeal carcinoma and to elucidate the underlying mechanisms. Methods: In this study, we used the nasopharyngeal carcinoma cell line 5-8F and a 5-8F xenograft mouse model to evaluate the anticancer effects of shikonin. The viability and morphology of cells treated with shikonin were evaluated using CCK-8 assay and transmission electron microscopy, respectively. In addition, the expression levels of RIPK1, RIPK3, and MLKL were analyzed by western blotting, and the activities of caspase-3 and caspase-8 and levels of reactive oxygen species (ROS) were assessed. Results: Shikonin exhibited a strong inhibitory effect on 5-8F cells in vitro and in vivo. The shikonin-treated 5-8F cells presented an electron-lucent cytoplasm, loss of plasma membrane integrity, and an intact nuclear membrane, indicating that shikonin induced necroptosis. Shikonin-induced cell death was inhibited by necrostatin-1. Moreover, RIPK1, RIPK3, and MLKL were upregulated by shikonin in a dose-dependent manner. Furthermore, shikonin significantly inhibited tumor growth in the 5-8F xenograft mouse model. Conclusion: Shikonin induced 5-8F cell death via increased ROS production and the upregulation of RIPK1/RIPK3/MLKL expression, resulting in necroptosis. Thus, shikonin may represent a novel agent to treat nasopharyngeal carcinoma.

[Expression and role of IL-33 and its receptor ST2 in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps].

OBJECTIVE: To investigate the expression and role of Interleukin-33 (IL-33) and ST2 in the nasal polyps of human Eosinophilic and non-Eosinophilic chronic rhinosinusitis with nasal polyps (ECRS and non-ECRS). METHOD: IL-33 and ST2 protein expression in nasal polyps of ECRS and non-ECRS as well as in seemingly normal mucosa of the inferior turbinate tissue was investigated by immunohistochemical staining and messenger RNA (mRNA) expression of IL-33 and ST2 was assessed by realtime polymerase chain reaction (PCR) in 27 subjects with ECRS, 33 subjects with non-ECRS, and 11 control subjects. RESULT: (1) The ST2 was found both in nasal polyps of ECRS and non-ECRS,especially in ECRS, yet hardly found in the normal mucosa of the inferior turbinate tissue; (2) The expression of ST2 mRNA in nasal polyps of ECRS was higher than that in non-ECRS and normal inferior turbinate tissue, and the difference was both prominent in statistics (P<0.01); (3) The expression patterns of IL-33 at both mRNA and protein levels were not significantly different among the three groups (P>0.05). CONCLUSION: The IL-33 and its receptor ST2 were both expressed in human nasal polyps including ECRS and non-ECRS, meanwhile the expression patterns of ST2 at both mRNA and protein levels were significantly higher in nasal polyps of ECRS. The current study suggests that IL-33 and its receptor ST2 may play important roles in the pathogenesis of chronic rhinosinusitis with nasal polyps, especially in ECRS through the increased expression of ST2 in Eosinophils as a hypothesis.