BackgroundAs the most populous nation in the world, China has now becoming an emerging ageing society. Shanghai is the first city facing the challenge of ageing demographics. Against this background, a study that employs self-rated health (SRH) assessment system was designed to explore the health status of Shanghai elders, and learn their attitudes toward health issues; as well as to investigate the determinants of SRH among Shanghai elders. Understanding SRH is crucial for finding appropriate solutions that could effectively tackle the increasing eldercare demand.MethodsThis study adopted a quantitative research strategy. Using a multistage stratified cluster sampling method, we conducted a questionnaire survey in August 2011 in Shanghai, which collected 2001 valid survey responses. SRH assessments were categorized by five levels: very good, fairly good, average, fairly poor, or poor. The respondents’ functional status was evaluated using the Barthel index of activities for daily living. In the data analysis, we used chi-squared test to determine differences in socio-demographic characteristics among various groups. Along with statistics, several logistic regression models were designed to determine the associations between internal influence factors and SRH.ResultsYounger age (χ2 = 27.5, p < 0.05), male sex (χ2 = 11.5, p < 0.1), and living in the suburbs (χ2 = 55.1, p < 0.05) were associated with better SRH scores. Higher SRH scores were also linked with health behaviour of the respondents; namely, do not smoke (χ2 = 18.0, p < 0.1), do not drink (χ2 = 18.6, p < 0.1), or engage in regular outdoor activities (χ2 = 69.3, p < 0.05). The respondents with better social support report higher SRH scores than those without. Respondents’ ability to hear (χ2 = 38.7, p < 0.05), speak (χ2 = 16.1, p < 0.05) and see (χ2 = 78.3, p < 0.05) impacted their SRH scores as well. Meanwhile, chronic illness except asthma was a major influence factor in low SRH score. Applying multiple regression models, a series of determinants were analysed to establish the extent to which they contribute to SRH. The impact of these variables on SRH scores were 6.6% from socio-demographic and health risk behaviours, 2.4% from social support, 8.5% from mental health, 20% from physical conditions, and13% from chronic diseases.ConclusionsThis is the first study that examines the determinants of SRH among Shanghai elders. Nearly 40% of our study’s respondents reported their health status as “good”. The main determinants of SRH among elders include living condition, health risk behaviour, social support, health status, and the economic status of the neighbourhood.
Angiogenesis is a key characteristic of asthma airway remodeling. By releasing cationic granule proteins, such as major basic protein (MBP), activated eosinophils play a prominent role in asthma, but the underlying mechanisms are still not fully understood. In this study, we demonstrated that fibroblast growth factor-binding protein 1 (FGFBP1) was dramatically upregulated in airway epithelial cell lines treated by poly-L-arginine (PLA), a mimic of MBP. Elevated FGFBP1 expression was also detected in asthma clinical samples, as well as in ovalbumin (OVA)-induced chronic asthma mouse models. PLA enhanced FGFBP1 expression through activation of the mechanistic target of rapamycin complex 1-signal transducer and activator of transcription 3 (mTORC1-STAT3) signaling pathway. STAT3 transactivated FGFBP1 by directly binding to the promoter of the FGFBP1 gene. Furthermore, we identified that FGFBP1 secreted by PLA-treated airway epithelial cells served as a proangiogenesis factor. Lastly, we found the mTORC1-STAT3-FGFBP1 signaling pathway was activated in an OVA-induced chronic asthma model with airway remodeling features. Rapamycin treatment alleviated respiratory symptoms and reduced angiogenesis in asthmatic mice. Therefore, activation of the mTORC1-STAT3-FGFBP1 pathway in the airway epithelium contributes to the progress of angiogenesis and should be targeted for the treatment of asthma.
Background: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck, and it has shown increasing incidence and mortality. The mechanistic target of rapamycin complex 1 (mTORC1) is frequently dysregulated in LSCC, but its underlying mechanisms remain unclear. Methods: Establishment of a novel LSCC cell line using primary LSCC tumor tissues with dysregulated mTORC1 activity and then stable knockdown of Raptor (an mTORC1 specific component) in this cell line. Transcriptomic sequencing, quantitative real-time PCR, western blot analysis, and immunofluorescence assays were used to identify the crucial downstream effector of mTORC1. A series of experiments were conducted to investigate the functions and underlying mechanisms of the mTORC1 target gene in LSCC progression. Clinical LSCC samples were used to evaluate the association of mTORC1 and its downstream targets with clinicopathological features and patient prognosis. Finally, the influence on cisplatin (CDDP) sensitivity upon depletion of the mTORC1 target gene was assessed using a cell culture system, a cell line-derived xenograft (CDX) model, and a patient-derived xenograft (PDX) model. Results:We successfully established a novel LSCC cell line with hyperactivated mTORC1 activity and then identified integrin subunit alpha 5 (ITGA5) as a novel functional downstream effector of mTORC1 in the progression of LSCC. Elevated ITGA5 promotes LSCC progression through augmentation of ephrin-B2 (EFNB2). Clinical data analysis indicated that the activation of the mTORC1-ITGA5-EFNB2 signaling pathway is associated with malignant progression and poor prognosis of LSCC patients. Inhibition of ITGA5 significantly sensitized LSCC cells to CDDP. Conclusions: Our findings highlight a novel molecular mechanism for the tumorigenesis driven by deregulated mTORC1 signaling in LSCC, suggesting that the ITGA5-EFNB2 axis may be a therapeutic target for the treatment of mTORC1-related LSCC.
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