1.Prediction of stroke-associated pneumonia in patients with acute ischemic stroke: comparison of 6 scores
Jing HANG ; Xiding PAN ; Niannian GE ; Yang YANG ; Junshan ZHOU ; Youyong TIAN
International Journal of Cerebrovascular Diseases 2017;25(11):972-978
Objective To investigate the predictive values of Kwon's score,Chumbler's score,Age,Atrial Fibrillation,Dysphagia,Sex,Stroke Severity (A2DS2) score,the Preventive ANtibacterial THERapy in Acute Ischemic Stroke (PANTHERIS) score,Acute Ischemic Stroke-Associated Pneumonia Score (AIS-APS),and prestroke Independence,Sex,Age,NIHSS (ISAN) score for stroke-associated pneumonia (SAP) in patients with acute ischemic stroke.Methods The patients with acute ischemic stroke were enrolled retrospectively.They were grouped according to whether to be complicated with SAP or not.The demography and baseline characteristics were compared between the SAP group and the non-SAP group.Multivariate logistic regression analysis was used to identify the independent risk factors for SAP.Receiver operating characteristic (ROC) curves were used to compare the predictive values of the 6 kinds of scores for SAP.Results A total of 1 427 patients with acute ischemic stroke were enrolled.Three hundred ninety-five patients (27.7%) complicated with SAP within 7 d after onset.There were significant differences in age,gender,past history (pneumonia,atrial fibrillation,smoking),laboratory tests (white blood cell count >11 × 109/L,baseline blood glucose ≥ 11.1 mmol/L),Oxfordshire Community Stroke Project (OCSP) classification,falling at the time of onset,dysphagia,mechanical ventilation and the modifiel Rankin Scale (mRS) score before onset,baseline Glasgow Coma Scale (GCS) score,baseline National Institutes of Health Stroke Scale (NIHSS) score and 6 scores between the SAP group and the non-SAP group (all P < 0.05).Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.034,95% confidence interval [CI] 1.019-1.049;P=0.001),white cell count > 11 × 109/L (OR 4.386,95%CI 2.763-6.905;P=0.001),baseline blood glucose ≥ 11.1 mmol/L (OR 1.933,95 % CI 1.305-2.864;P =0.001),dysphagia (OR 7.839,95% CI 4.892-12.563;P =0.001),baseline NIHSS (OR 1.120,95% CI 1.077-1.165;P =0.001),and baseline GCS score (OR 1.132,95% CI 1.019-1.257;P =0.021) were the independent risk factors for SAP.The areas under the ROC curves of SAP predicted by the Chumbler's,AIS-APS,A2DS2,ISAN,Kwon's and PANTHERIS scores were 0.830 (95% CI 0.805-0.855),0.827 (95% CI 0.802-0.852),0.818 (95% CI 0.792-0.845),0.788 (95% CI 0.762-0.814),0.774 (95%CI 0.774-0.803),and 0.727 (95% CI 0.695-0.758),respectively.There were no significant differences in the area under ROC curves of Chumbler's,A2DS2 and AIS-APS scores between the pairwise comparisons.There were significant differences in the area under ROC curves of the Chumbler's,A2DS2,AIS-APS and ISAN scores between the pairwise comparisons (AIS-APS compared with ISAN:P =0.001;the rests P < 0.001).Conclusions The accuracies of predicting SAP with the Chumbler's,AIS-APS and A2DS2 scores are superior to the ISAN,Known's and PANTHERIS scores,and have higher clinical application value.
2.Effects of the interaction between Brahma-related gene 1 and activating transcription factor 2 on the proliferation, migration and invasion of cutaneous squamous cell carcinoma cells
Li ZHANG ; Jian SHI ; Xin GE ; Niannian LIU ; Sai CHEN ; Dongmei ZHANG ; Xu MIAO
Chinese Journal of Dermatology 2023;56(8):724-736
Objective:To determine the expression of Brahma-related gene 1 (BRG1) in cutaneous squamous cell carcinoma (cSCC) tissues and cells, and to investigate molecular mechanisms underlying the regulatory effect of its interaction with activating transcription factor 2 (ATF2) on the proliferation, migration and invasion of cSCC cells.Methods:From 2015 to 2021, 66 paraffin-embedded actinic keratosis (AK) tissue samples and 80 paraffin-embedded cSCC (including squamous cell carcinoma in situ) tissue samples were collected from the Department of Dermatology, Affiliated Hospital 2 of Nantong University, and the diagnoses of all the cases were confirmed histopathologically; at the same time, 35 paraffin-embedded normal skin tissue samples obtained by cosmetic surgery served as normal control group. Immunohistochemical staining was performed to determine the BRG1 expression in cSCC, AK, and normal skin tissues, and correlations between BRG1 expression and clinicopathological parameters of cSCC patients were analyzed. Fresh tissue samples were collected from 12 cSCC patients and 12 healthy controls, and cSCC cell lines A431 and Scl-1 and a human immortalized keratinocyte cell line HaCaT were routinely cultured; real-time fluorescence-based quantitative PCR (qRT-PCR) was performed to determine the mRNA expression of BRG1 in tissues and cells, and co-immunoprecipitation assay and cellular immunofluorescence staining were conducted to analyze the interaction between BRG1 and ATF2. The expression of BRG1 (BRG1 siRNA1 - 5 groups) and ATF2 (ATF2-shRNA group) in A431 and Scl-1 cells was knocked down by RNA interference, and cells transfected with negative control siRNA or shNC served as controls (control siRNA group and shNC group, respectively), cell counting kit-8 (CCK8) assay, colony formation assay, cell scratch assay, and Transwell assay were conducted to evaluate effects of knocking down BRG1 and ATF2 on the proliferation, migration, and invasion of cSCC cells. Comparisons of measurement data among multiple groups were conducted using one-way analysis of variance, and multiple comparisons were conducted using Dunnett- t test. Results:Immunohistochemical staining showed that the expression intensity of BRG1 protein was significantly lower in the cSCC and AK tissues than in the normal skin tissues ( χ2 = 44.40, P < 0.001). qRT-PCR showed that the mRNA expression level of BRG1 was significantly lower in the cSCC tissues (1.345 ± 0.956) than in the normal skin tissues (2.499 ± 1.501, t = 2.25, P = 0.035), and also significantly lower in A431 and Scl-1 cells (0.041 ± 0.002, 0.026 ± 0.003, respectively) than in HaCaT cells (0.135 ± 0.033, t = 4.95, 5.73, P = 0.008, 0.005, respectively). The low expression of BRG1 was associated with tumors at sun-exposed sites ( P = 0.041), low tumor differentiation ( P = 0.001), and high Broder′s grade ( P < 0.001) in the cSCC patients. In both A431 cells and Scl-1 cells, the BRG1 siRNA1 group and BRG1 siRNA2 group showed significantly increased numbers of cell colonies, migratory cells and invasive cells, as well as cell migration rates compared with the control siRNA group (all P < 0.05). Co-immunoprecipitation assay showed that BRG1 protein could bind to ATF2 protein in A431 and Scl-1 cells, and immunofluorescence staining showed that the two proteins were co-localized; compared with the control siRNA group, the BRG1 siRNA1 group (both A431 and Scl-1 cells) and BRG1 siRNA2 group (A431 cells) both showed increased phosphorylation and activation of ATF2 (all P < 0.05) ; in both A431 cells and Scl-1 cells, the shATF2 group showed significantly decreased numbers of cell colonies (both P = 0.001), cellular proliferative activity at 24 - 96 hours (all P < 0.001), and numbers of migratory cells and invasive cells compared with the shNC group (all P ≤ 0.001) . Conclusion:BRG1 was lowly expressed in the cSCC and AK tissues, and could inhibit the proliferation, migration, and invasion of cSCC cells; ATF2 could promote the proliferation, migration, and invasion of cSCC cells; BRG1 may exert an anti-tumor effect by interacting with ATF2 protein and inhibiting phosphorylation-dependent activation of ATF2.