Objective:The mucosa of Chronic rhinosinusitis with nasal polyps（CRSwNP） is accompanied by tissue remodeling. Epithelial-mesenchymal transition（EMT） plays an important role in tissue remodeling, but the mechanism of EMT is not yet clear. The purpose of this study is to further clarify the pathogenesis of CRSwNP and provide another idea and theoretical basis for the treatment of CRSwNP. Methods:①The expression of NLRP3 and EMT-related protein（E-cadherin, Vimentin） in the nasal mucosa of the CRSwNP group and the normal control group were detected by immunohistochemistry（IHC）. ②Primary human nasal epithelial cells（HNECs） were cultured in vitro, and HNE-intervened cells with different concentrations（0, 10, 25, 50, 100 ng/mL） were used. After stimulation for 24 h, mRNA and protein expressions of E-cadherin, Vimentin, NLRP3 were detected by qRT-PCR and western blotting. ③Cells were collected at 0, 24, 36, 48 and 72 hours later after incubation with HNE with the optimal concentration, and the mRNA and protein expressions of E-cadherin, Vimentin and NLRP3 were detected by qRT-PCR and western blotting. ④Primary human nasal epithelial cells were pretreated with NLRP3 inhibitor MCC950, then stimulated with HNE, and EMT-related proteins（E-cadherin, Vimentin） and NLRP3 expression were detected by qRT-PCR and western blotting. Results:①The expression levels of NLRP3 and Vimentin in nasal polyps of CRSwNP patients were higher than those of control group, and the expression of E-cadherin was lower（P<0.05）. The mRNA and protein expression levels of NLRP3 and Vimentin increased when HNE stimulated primary human nasal epithelial cells, while the expression of E-cadherin decreased. ②The effect was most significant when the HNE stimulated nasal mucosal epithelial cells were exposed to 50 ng/mL（P<0.05）. The primary human nasal epithelial cells were stimulated with 50 ng/ml HNE, and the effect was most significant when the duration of HNE exposure was 36 h（P<0.05）. ③Primary human nasal epithelial cells were pretreated with MCC950 and then stimulated with HNE. The mRNA and protein expression levels of E-cadherin in the NLRP3 inhibitor pretreated group were increased, while the mRNA and protein expression levels of Vimentin and NLRP3 were decreased（P<0.05）. Conclusion:ln CRSwNP, HNE promotes EMT in human nasal mucosal epithelial cells by activating NLRP3.
Humans ; Nasal Polyps/metabolism* ; Epithelial-Mesenchymal Transition ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Sinusitis/metabolism* ; Cadherins/metabolism* ; Vimentin/metabolism* ; Chronic Disease ; Nasal Mucosa/cytology* ; Rhinitis/metabolism* ; Epithelial Cells/metabolism* ; Cells, Cultured ; Rhinosinusitis

Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.

BACKGROUND/OBJECTIVES: The specific impact of different fruit and vegetable consumption categories on frailty is not completely understood. This study examined the relationships between the daily consumption of fruit and vegetables and frailty in a large general population. SUBJECTS/METHODS: This study used the data from the US National Health and Nutrition Examination Survey (2005–2020). Two intermittent 24-h dietary recalls were used to evaluate fruit and vegetable consumption. Frailty was assessed using the frailty index. Logistic regression, stratified analyses, and restricted cubic spline models were used to examine these associations. RESULTS: A higher daily intake of citrus, melons, and berries (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.65–0.92), other fruit (OR, 0.74; 95% CI, 0.62–0.88), intact fruit (OR, 0.71; 95% CI, 0.60–0.84), dark-green vegetables (OR, 0.71; 95% CI, 0.60–0.83), and total vegetables (OR, 0.80; 95% CI, 0.66–0.96), along with a lower fruit juice intake (OR, 0.81; 95% CI, 0.69–0.96), were associated with a reduced risk of frailty in adults aged 18 yrs and older.Further analysis showed that the daily consumption of citrus melons and berries, other fruit, intact fruit, fruit juice, and tomatoes and tomato products were inversely associated with frailty in adults under 60 yrs and females. Dark green vegetables were inversely correlated with frailty in individuals aged 40–60 yrs and over 60 yrs, regardless of sex. CONCLUSION The daily consumption of most types of fruit, dark green vegetables, and tomatoes and tomato products may reduce the risk of frailty in American adults, particularly for individuals under 60 yrs of age and females.

BACKGROUND/OBJECTIVES: The specific impact of different fruit and vegetable consumption categories on frailty is not completely understood. This study examined the relationships between the daily consumption of fruit and vegetables and frailty in a large general population. SUBJECTS/METHODS: This study used the data from the US National Health and Nutrition Examination Survey (2005–2020). Two intermittent 24-h dietary recalls were used to evaluate fruit and vegetable consumption. Frailty was assessed using the frailty index. Logistic regression, stratified analyses, and restricted cubic spline models were used to examine these associations. RESULTS: A higher daily intake of citrus, melons, and berries (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.65–0.92), other fruit (OR, 0.74; 95% CI, 0.62–0.88), intact fruit (OR, 0.71; 95% CI, 0.60–0.84), dark-green vegetables (OR, 0.71; 95% CI, 0.60–0.83), and total vegetables (OR, 0.80; 95% CI, 0.66–0.96), along with a lower fruit juice intake (OR, 0.81; 95% CI, 0.69–0.96), were associated with a reduced risk of frailty in adults aged 18 yrs and older.Further analysis showed that the daily consumption of citrus melons and berries, other fruit, intact fruit, fruit juice, and tomatoes and tomato products were inversely associated with frailty in adults under 60 yrs and females. Dark green vegetables were inversely correlated with frailty in individuals aged 40–60 yrs and over 60 yrs, regardless of sex. CONCLUSION The daily consumption of most types of fruit, dark green vegetables, and tomatoes and tomato products may reduce the risk of frailty in American adults, particularly for individuals under 60 yrs of age and females.

Objective: To explore the prevalence of elevated blood pressure and overweight/obesity and their comorbidities among Tibetan middle school students in Lhasa, and to analyze their association with lifestyle and other factors, so as to provide a basis for the intervention measures targeting elevated blood pressure, overweight and obesity among middle school students in high altitude area. Methods: Using a stratified cluster random sampling method in September 2021, a total of 1 488 Tibetan junior and high students from Lhasa City were investigated with blood pressure measurement, physical examination and questionnaire survey. The influencing factors of elevated blood pressure, overweight and obesity and their comorbidities association were analyzed by multivariate Logistic regression. Results: The prevalence of elevated blood pressure, overweight/obesity and their comorbidities were 17.8%, 17.4% , 5.0% respectively. Multivariate Logistic regression analysis showed that age( OR =0.81), residence, body mass inex(BMI) and gender were the influencing factors of elevated blood pressure; and the risks of elevated blood pressure in female students were higher than male students ( OR =1.89), suburban students were higher than urban students ( OR =8.06), overweight and obesity groups were higher than normal groups ( OR =2.55, 2.87) ( P <0.05). Adjusting for confounding factors such as gender, residence and school, and BMI (only for elevated blood pressure), daily screen time ≥2 h was positively correlated with elevated blood pressure, overweight/obesity and its comorbidities ( OR =1.56, 1.59 , 2.51) ( P <0.05). Conclusions The prevalence of elevated blood pressure, overweight/obesity are relatively high in Lhasa. Longer screen time is a common factor affecting with elevated blood pressure, overweight/obesity and comorbidities among Tibetan students. Measures should be taken intervene in the lifestyle of Tibetan students, in order to reduce elevated blood pressure and overweight/obesity.

BACKGROUND/OBJECTIVES: The specific impact of different fruit and vegetable consumption categories on frailty is not completely understood. This study examined the relationships between the daily consumption of fruit and vegetables and frailty in a large general population. SUBJECTS/METHODS: This study used the data from the US National Health and Nutrition Examination Survey (2005–2020). Two intermittent 24-h dietary recalls were used to evaluate fruit and vegetable consumption. Frailty was assessed using the frailty index. Logistic regression, stratified analyses, and restricted cubic spline models were used to examine these associations. RESULTS: A higher daily intake of citrus, melons, and berries (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.65–0.92), other fruit (OR, 0.74; 95% CI, 0.62–0.88), intact fruit (OR, 0.71; 95% CI, 0.60–0.84), dark-green vegetables (OR, 0.71; 95% CI, 0.60–0.83), and total vegetables (OR, 0.80; 95% CI, 0.66–0.96), along with a lower fruit juice intake (OR, 0.81; 95% CI, 0.69–0.96), were associated with a reduced risk of frailty in adults aged 18 yrs and older.Further analysis showed that the daily consumption of citrus melons and berries, other fruit, intact fruit, fruit juice, and tomatoes and tomato products were inversely associated with frailty in adults under 60 yrs and females. Dark green vegetables were inversely correlated with frailty in individuals aged 40–60 yrs and over 60 yrs, regardless of sex. CONCLUSION The daily consumption of most types of fruit, dark green vegetables, and tomatoes and tomato products may reduce the risk of frailty in American adults, particularly for individuals under 60 yrs of age and females.