Risk stratification of delayed causative aneurysm detection and long-term outcome in angiographically negative spontaneous subarachnoid haemorrhage.

BACKGROUND: The risk factors of aetiology and poor outcome in angiographically negative subarachnoid haemorrhage (anSAH) were unclearly. METHODS: The authors performed a retrospective review of a prospectively maintained database for anSAH patients between 2014 and 2018. AnSAH was defined as SAH presents in CT with no underlying vascular abnormality on initial digital subtraction angiography (DSA) within 72 hours of admission. Baseline and follow-up information, including medical history, bleeding pattern (perimesencephalic angiogram-negative SAH (PAN-SAH) and non-PAN-negative SAH (NPAN-SAH)), modified Fisher Scale (mFS), Glasgow Coma Score (GCS), Hunt-Hess grade, repeated imaging and causative vascular lesions and follow-up modified Rankin Scale (mRS) were reviewed. Poor outcome was defined as mRS scored 3-6 at last clinical follow-up. RESULTS: Among 303 enrolled patients, 272 patients underwent at least once repeated imaging examination (median follow-up time, 3.0 months). Twenty-one (7.7%) aneurysms were detected. Multivariate logistic analysis showed that NPAN-SAH and mFS 3-4 were associated with a high rate of aneurysm detection in anSAH patients. Based on risk stratification, the aneurysm detection rate in the high-risk group (both NPAN-SAH and mFS 3-4) was as high as 20.370 per 100 person-years. Furthermore, of 251 non-aneurysm anSAH patients, after a total follow-up time of 1265.83 patient-years, poor outcome occurred in 18 (7.2%) patients. Multivariate Cox analysis found that NPAN-SAH and GCS 3-12 were associated with a high rate of poor outcome of anSAH. The cumulative 5-year incidence rate for poor outcome in the non-aneurysm anSAH patients in the high-risk group (both NPAN-SAH and GCS 3-12) was as high as 75.302 per 100 person-years. CONCLUSIONS: Even in anSAH confirmed by initial DSA, patients with NPAN-SAH and mFS 3-4 should be monitored for delayed causative aneurysm detection, meanwhile in non-aneurysm anSAH patients, NPAN-SAH and initial functional impairment are associated with poor prognosis.

CRABP2 involvement in a mechanism of Golgi stress and tumor dry matter in non-small cell lung cancer cells via ER dependent Hippo pathway.

OBJECTIVE: The paper aimed to explore the mechanism of cellular retinoic acid binding protein 2 (CRABP2) involvement in Golgi stress and tumor dryness in non-small cell lung cancer (NSCLC) cells through the estrogen receptor (ER) dependent Hippo pathway. METHODS: Human NSCLC cell line A549 was purchased from ATCC andcultured in RPMI-1640 with 10% FBS. Attractene reagent was used for plasmid transfection. ER (sh) RNA was designed using RNAi Designer. Seventy-six hours after infection, stable cells were obtained after treated with puromycin for 3 weeks. ER silencing cells (with inhibited ER expression) were compared to the control cells (normal cultured NSCLC cell line A549, CRABP2 normal expression). CRABP2 and ER expression levels were detected by RT-PCR. MTT assay was used to detect cell proliferation, and the cell localization of ER and Golgi was observed by confocal microscopy. The invasion and metastasis of cells were analyzed by Boden chamber invasion and migration assays. Western blotting assays was used for detecting the protein expression of E-cadherin, vimentin, ZO-1 protein and epithelial-mesenchymal transition (EMT) related factors. RESULTS: The lower expression level of mRNA was detected in the ER-silencing group compared to the control group (P<0.05). We also found a higher proliferation level of cells, the number of invading and metastatic cells, the expression of vimentin, p-Lats1T1079, Lats1 and p-YAPS127 mRNA in the control group compared to the ER silencing group (P<0.05). And the expression level of protein kinase RNA-like endoplasmic reticulum kinase (PERK), phosphorylate eukaryotic initiation factor 2 (p-eIF2 alpha), activating transcription factor 4 (ATF4) and C/EBP-homologous protein (CHOP) in the control group was higher than that in the ER silencing group (P<0.05). Adversely, a lower expression level of E-cadherin and ZO-1 protein was found in the control group compared to the ER silencing group (P<0.05). CONCLUSION: The expression of CRABP2 in NSCLC cells was regulated by ER, and cell proliferation and invasion were regulated by the Hippo pathway. At the same time, it was found that decreased expression of CRABP2 enhanced endoplasmic reticulum/Golgi stress response.

Knockdown of miR-543 Inhibits the Proliferation and Migration of Small-Cell Lung Carcinoma Cells and Induces Apoptosis.

This article aims to explore the effects and possible mechanism of miR-543 on small-cell lung carcinoma (SCLC) cells. The respective levels of miR-543 in lung carcinoma tissues, para-cancerous tissues, human normal lung cells MRC-9, and SCLC cells were detected by RT-qPCR. The proliferation, apoptosis, and migration of SCLC cells were detected after the miR-543 level in SCLC cells was altered by miRNA mimics and inhibitors. The levels of apoptosis-related proteins and potential downstream targeted proteins of miR-543 were detected by western blots. The study revealed that KNTC1 was highly expressed in lung carcinoma tissues and SCLC cells (P < 0.01). It also showed that knockdown of miR-543 can inhibit the proliferation and migration of SCLC cells, induce apoptosis, and increase the level of apoptosis-related proteins. These changes were reversed by the addition of mimics that increased miR-543 levels. The level of miR-543 was positively correlated with the protein expression level of downstream MUC1, ß-catenin, and CDC42 in SCLC cells, suggesting that miR-543 may play a role through them. Thus this study concludes that MiR-543 can affect the function of SCLC cells, which may play a crucial role in the presence and development of SCLC.

Correlation between Plasma Cellular Retinoic Acid-Binding Protein 2 and Proliferation, Migration, and Invasion of Non-Small-Cell Lung Cancer Cells.

BACKGROUND: Our primary aim of the current study was to explore the correlation between plasma CRABP2 and migration, proliferation and invasion of non-small cell lung cancer (NSCLC) cells. METHODS: Human lung cancer cell line A549 was used in the present study, which was cultured in 6-well plates (1 × 106 cells/well) and then transfected with pcDNA-CRABP2 and pcDNA, siRNA with the use of Lipofectamine 2000 based on the manufacturer's protocol. The expression of CRABP2 mRNA was detected through real-time PCR. Proliferation was further detected using MTT assays, and apoptosis was monitored and recorded with the application of flow cytometry. The expression of E-cadherin, MMP9, vimentin and related pathway proteins was detected by Western blotting assays. Transwell assays and cell scratch assays were utilized for the detection of migration and invasion ability of A549 cells. RESULTS: RT-PCR results showed The CRABP2 mRNA transcript levels in the CRABP2 overexpression group were higher when comparing those of the empty vector group (P < 0.05). By MTT assays, CRABP2 overexpression promoted cellular proliferation, while CRABP2 downregulation inhibited cellular proliferation. CRABP2 overexpression inhibited cell apoptosis and promoted cellular proliferation. The number of TUNEL staining positive cells was the lowest in the CRABP2 overexpression group, and the siRNA transfection group had increased apoptosis. CRABP2 downregulation reduced EMT in cells and cell migration and invasion reflected from western blotting results and cell migration and invasion assay results, respectively. CONCLUSION: Inhibition of plasma CRABP2 expression offers the potential in terms of reducing the expression of MAPKs and proteins in the NF-κB pathway and inhibiting the proliferation and migration of NSCLC cells, which is ideally suited for further treatment for NSCLC.

Efficacy of tiotropium in treating patients with moderate-to-severe asthma: A meta-analysis and systematic review based on 14 randomized controlled trials.

BACKGROUND: The goal of the current meta-analysis and systematic review was to explore the efficacy of tiotropium in treating patients with moderate-to-severe asthma on the basis of qualified randomized controlled trials (RCTs). METHODS: The following online electronic databases, such as Cochrane, PubMed, and Embase database were screened to identify qualified studies updated to January 2019 through the use of index words. Several literatures that were relevant to the present analysis were also included. To further analyze the main outcomes, we utilized the odds rations (OR), and mean difference (MD) along with its 95% confidence interval (95% CI). RESULTS: A total of 14 RCTs with 4998 patients in the tiotropium group and 5074 patients in the control group were included in the present study. On the basis of the pooled results, tiotropium was significantly associated with improved morning PEF (SMD: 3.29, 95%CI: 2.03-4.55), evening PEF (SMD: 3.36, 95%CI: 2.24-4.48), peak FEV (SMD: 2.67, 95%CI: 1.47-3.88), and trough FEV (SMD: 1.90, 95%CI: 0.87-2.92) vs the control group. Nevertheless, no significant difference was observed in peak FVC (SMD: 0.77, 95%CI: -0.21-1.76), trough FVC (SMD: 0.67, 95%CI: -0.18-1.53), AE (RR: 0.98, 95%CI: 0.94-1.02) and serious AE (RR: 1.08, 95%CI: 0.77-1.52) between the 2 groups. CONCLUSIONS: In this review, we summarized the significant effect of tiotropium for the treatment of moderate-to-severe asthma, mainly in increasing morning PEF, evening PEF, peak FEV and trough FEV based on high-quality RCTs. Nevertheless, no significant difference in peak FVC, trough FVC, AE and serious AE was found between the 2 groups. A close comparison of the 2 groups revealed that more high-quality larger-sample RCTs are needed to gather more strong evidence on the therapeutic efficacy and safety of tiotropium for clinical practice.

Unraveling the genetic basis of asthma and allergic diseases.

Asthma and allergic diseases are believed to be complex genetic diseases which may result from the interaction of multiple genetic factors and environmental stimuli. In past decades, great efforts have been exerted in unraveling their genetic basis. The strategies in discovering genes and genetic variants, confirming their importance in pathogenesis of asthma and allergic diseases, as well as their strengths and limitations are summarized comprehensively and concisely. The current consensus about the genetic basis of asthma and allergic diseases is briefly described as well.