ABSTRACT
BACKGROUND: Stimulator of interferon genes (STING) activation favors effective innate immune responses against viral infections. Its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown. OBJECTIVE: Our aim was to explore the expression, regulation, and function of STING in CRSwNP. METHODS: STING expression in sinonasal mucosal samples was analyzed by means of quantitative RT-PCR, immunohistochemistry, flow cytometry, and Western blotting. Regulation and function of STING expression were explored by using cultured primary human nasal epithelial cells (HNECs) and cells of the line BEAS-2B in vitro. RESULTS: STING expression was reduced in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues. STING was predominantly expressed by epithelial cells in nasal tissue and was downregulated by IL-4 and IL-13 in a signal transducer and activator of transcription 6 (STAT6)-dependent manner. HNECs derived from eosinophilic polyps displayed compromised STING-dependent type I interferon production but heightened IL-13-induced STAT6 activation and CCL26 production as compared with HNECs from noneosinophilic polyps and control tissues, which were rescued by exogenous STING overexpression. Knocking down or overexpressing STING decreased or enhanced expression of suppressor of cytokine signaling 1 (SOCS1) in BEAS-2B cells, respectively, independent of the canonic STING pathway elements TBK1 and IRF3. Knocking down SOCS1 abolished the inhibitory effect of STING on IL-13 signaling in BEAS-2B cells. STING expression was positively correlated with SOCS1 expression but negatively correlated with CCL26 expression in nasal epithelial cells from patients with CRSwNP. CONCLUSIONS: Reduced STING expression caused by the type 2 milieu not only impairs STING-dependent type I interferon production but also amplifies IL-13 signaling by decreasing SOCS1 expression in nasal epithelial cells in eosinophilic CRSwNP.
Subject(s)
Eosinophilia/immunology , Interleukin-13/immunology , Membrane Proteins/immunology , Nasal Polyps/immunology , Rhinitis/immunology , Sinusitis/immunology , Adult , Cells, Cultured , Chronic Disease , Epithelial Cells/immunology , Female , Fetal Proteins/genetics , Gene Knockdown Techniques , Humans , Interferon Regulatory Factor-3/genetics , Male , Membrane Proteins/genetics , Middle Aged , Nasal Mucosa/cytology , Protein-Tyrosine Kinases/genetics , Suppressor of Cytokine Signaling 1 Protein/geneticsABSTRACT
OBJECTIVE: To describe the duration of the pre-hospital delay time and identify factors associated with prolonged pre-hospital delay in patients with acute myocardial infarction (AMI) in China. METHODS: Data were collected from November 2014 to December 2019 as part of the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project. A total of 33,386 patients with AMI admitted to the index hospitals were included in this study. Two-level logistic regression was conducted to explore the factors associated with the pre-hospital delay and the associations between different pre-hospital delay and in-hospital outcomes. RESULTS: Of the 33,386 patients with AMI, 70.7% of patients arrived at hospital ≥ 2 h after symptom onset. Old age, female, rural medical insurance, symptom onset at early dawn, and non-use of an ambulance predicted a prolonged pre-hospital delay (all P < 0.05). Hypertension and heart failure at admission were only significant in predicting a longer delay in patients with ST-segment elevation myocardial infarction (STEMI) (all P < 0.05). A pre-hospital delay of ≥ 2 h was associated with an increased risk of mortality [odds ratio (OR) = 1.36, 95% CI: 1.09-1.69, P = 0.006] and major adverse cardiovascular events (OR = 1.22, 95% CI: 1.02-1.47, P = 0.033) in patients with STEMI compared with a pre-hospital delay of < 2 h. CONCLUSIONS: Prolonged pre-hospital delay is associated with adverse in-hospital outcomes in patients with STEMI in China. Our study identifies that patient characteristics, symptom onset time, and type of transportation are associated with pre-hospital delay time, and provides focuses for quality improvement.
ABSTRACT
The aim of this study was to explore the root morphology and root canal configuration of first premolars among Shandong Chinese residents using cone-beam computed tomography (CBCT).Randomly selected CBCT images were collected from 648 patients (44% women, 56% men). In total, 1268 maxillary and 1296 mandibular first premolars were analyzed. The number of roots and the canal configuration were recorded and identified based on Vertucci's classification.The majority of the maxillary first premolars had 1 root (67.4%), followed by 2 roots (32%). A 2-canal configuration (89%) was the most prevalent observation. For mandibular first premolars, 98.8% had 1 root and 81% presented the type I configuration. There were no statistical differences in the number of roots or morphology in terms of the left/right side or sex (Pâ>â.05).Among Chinese residents, the majority of maxillary first premolars had 1 root and 2 canals, whereas the most common anatomical configuration for mandibular first premolars was 1 root with 1 canal.
Subject(s)
Bicuspid/diagnostic imaging , Cone-Beam Computed Tomography , Tooth Root/diagnostic imaging , Adolescent , Adult , Aged , Anatomic Variation , Asian People , Female , Humans , Male , Mandible , Maxilla , Middle Aged , Young AdultABSTRACT
Low-frequency stimulation (LFS) has been considered as a new option for the treatment of intractable epilepsy. The present study was designed to determine whether LFS of the kindling focus given at different time points after seizures exert different roles on kindling seizures. Our results showed that: (i) In kindling animals, LFS delivered immediately after cessation of the kindling stimulus inhibited the seizure stage during kindling acquisition, whereas LFS delivered after the cessation of afterdischarge accelerated the kindling progression to stages 1 and 2. (ii) In fully kindled animals, when using the generalized seizure threshold current as the kindling stimulus, immediate LFS decreased the incidence of generalized seizures and the average seizure stage as well as shortened the cumulative generalized seizure duration (GSD). However, delayed LFS prolonged the cumulative GSD and afterdischarge duration. Our study indicates that there is a time-dependent aspect of LFS treatment, and immediate LFS has anti-epileptogenic action.