BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Allergic rhinitis(AR)is a type Ⅰ allergic reaction,which mediated by immunoglobulin E immediately when an individual with a special constitution is exposed to a same allergen for second time,whose pathogenesis has not been clarified yet,and closely related to genes,immune cells and cytokines.Pathogenesis of AR become more deeper and more accurate due to rapid develop-ment of molecular biology and second-generation gene sequencing technology.Current studies have found that miR-155 and transcrip-tion factor GATA3 have important regulatory effects on occurrence and development of AR,then affect dominant differentiation of CD4+T lymphocytes and proliferation of ILC2.This article discusses and reviews pathogenesis of AR,which mainly focuses on miR-155/GATA3 pathway and effects of related upstream genes and downstream regulatory substances.

ObjectiveTo analyze the long-term survival of non-small cell lung cancer （NSCLC） patients treated with Fuzheng Gushe therapy in the real world. MethodA retrospective cohort study was carried out with the NSCLC patients treated with Fuzheng Gushe therapy from January 2014 to December 2018 in Dongzhimen Hospital， Beijing University of Chinese Medicine as the integrated traditional Chinese medicine （TCM） and western medicine cohort. The NSCLC data from January 2011 to December 2015 in the Surveillance， Epidemiology， and End Results （SEER） database were downloaded as the western medicine cohort. The propensity score matching （PSM） was employed to balance the confounding factors between the groups， and comparable samples were obtained from the two groups. The Log-rank test was conducted to compare the overall survival between the groups and the survival curves were established. ResultThe integrated TCM and western medicine cohort and the western medicine cohort included 511 and 5 022 NSCLC patients， respectively. The age， sex， and chemotherapy had no significant differences between the two cohorts， while pathological type， lymph node metastasis （N）， distant metastasis （M）， surgery， and radiotherapy were different between the two cohorts （P<0.05）. After PSM， 122 comparable samples were obtained. The overall survival analysis showed that the total survival of the integrated TCM and western medicine cohort was better than that of the western medicine cohort （P<0.05）. The stratified survival analysis showed that the integrated TCM and western medicine cohort had survival advantages in females， males， the young， and adenocarcinoma， N+， and M+ patients （P<0.05）. ConclusionFuzheng Gushe therapy can significantly improve the overall survival of NSCLC patients， especially in the females， the males， the young， and the patients with adenocarcinoma， lymph node metastasis， and distant metastasis.

Objective Constructing a risk prediction model of IgA nephropathy proteinuria treated by traditional Chinese medicine based on random survival forest model,Screening prognostic risk factors of IgA nephropathy proteinuria.Methods Collecting retrospectively clinical data of 129 cases diagnosed with IgA nephropathy,randomly divided them into training set(60%)and test set(40%).The risk prediction model of IgA nephropathy proteinuria was constructed in the training set with the random survival forest model,and the prognostic risk factors were screened by VIMP method.The accuracy of risk prediction model was validated in the test set with time-dependent ROC curve(tdROC).Results According to the result of VIMP,the prognostic risk factors for IgA nephropathy proteinuria are in the order of eGFR,hypertension,traditional Chinese medicine,24 hUPRO>1 g,genomo sclerosis ratio,Lee grading,fat,hyperlipidemia,hypertrophymia,hyparmane ledmia,Anemia,age and gender.The eGFR was negatively and non-linearly associated with the risk rate of developing persistent proteinuria.Glomerulosclerosis ratio greater than 0.3 is approximately linearly and positively associated with the risk rate of persistent proteinuria.Conclusion Random survival forest model has good predictive performance in the risk prediction model of IgA nephropathy proteinuria treated by traditional Chinese medicine.This risk model can determine the result of IgA nephropathy treated by traditional Chinese medicine,and which is helpful for clinical follow-up monitoring and formulation of individualized treatment plans.

ObjectiveTo investigate the therapeutic effect of Qingmei compound on acute gouty arthritis （AGA） in rats and preliminarily clarify its mechanism. MethodForty male SD rats were randomly divided into a blank group， a model group， a colchicine group （0.3 mg·kg^-1）， and low- and high-dose Qingmei compound groups （200 and 400 mg·kg^-1）， with eight rats in each group. The AGA model was induced by injecting 50 g·L^-1 monosodium urate （MSU） into the ankle joint of the rats except those in the blank group. The ankle swelling index was measured before and 6， 24， and 48 h after modeling. The pathological changes in the joint tissues of AGA rats were observed by hematoxylin-eosin （HE） staining. The expression of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the joint tissues of rats was detected by immunohistochemistry. The protein expression of NOD-like receptor protein 3 （NLRP3） pathway and key proteins in the joint tissues of rats was detected by Western blot. ResultCompared with the blank group， the model group showed increased ankle swelling index， synovial hyperplasia， and inflammatory infiltration， and up-regulated expression of IL-1β， TNF-α， and NLRP3 proteins in the ankle joint and the ratio of Caspase-1 shear body to Caspase-1 precursor protein （Caspase-1 p20/Caspase-1） （P<0.01）. Compared with the model group， the Qingmei compound groups showed reduced ankle swelling index of AGA rats， especially the low-dose Qingmei compound group （P<0.01）. Meanwhile， Qingmei compound inhibited synovial hyperplasia and inflammatory infiltration （P<0.01） and reduced the levels of IL-1β， TNF-α， and NLRP3 proteins and Caspase-1 p20/Caspase-1 in joint tissues （P<0.01）. ConclusionQingmei Compound can significantly alleviate the joint swelling and inflammatory infiltration of AGA， and its mechanism may be related to the inhibition of the NLRP3 signaling pathway.

ObjectiveTo explore the mechanism of Yishen Huoxue prescription in renal interstitial fibrosis （RIF） from the perspective of endothelial cell and cell energy metabolism. MethodThe model was successfully established by unilateral ureteral obstruction （UUO）. Seventy-five SPF C57BL/6 mice were randomly divided into a model group， a resveratrol group （50 mg·kg^-1·d^-1）， three Yishen Huoxue prescription low， medium， and high-dose groups （7.1， 14.2， 28.4 g·kg^-1·d^-1）， with 15 mice in each group. In addition， another 15 mice were used to prepare sham operation model. Mice in the sham operation group and the model group were gavaged with equal volume of normal saline. All mice were sacrificed on 7， 14， and 21 d after modeling. The protein expression of platelet endothelial cell adhesion molecule 31 （CD31） was detected by immunohistochemical S-P method. The expression of α-smooth muscle actin （α-SMA）， collagen Ⅳ （Col-Ⅳ）， angiopoietin 1（Ang-1） and tyrosine kinase receptors 2 （Tie-2）， vascular endothelial growth factor （VEGF）， vascular endothelial cadherin （VE-cadherin）， and occludin in renal tissues was detected by Western blotting. The mRNA expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin in renal tissues were detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the levels of reactive oxygen species （ROS） in mice were detected by enzyme linked immunosorbent assay （ELISA）. ResultAs compared with the sham operation group， the expression of CD31 in renal tissues of the model group was significantly decreased and worsened with the extension of modeling time （P<0.05）， α-SAM and Col-Ⅳ protein expression levels were significantly increased （P<0.01）， but the expression of CD31 was stable in 14-21 d. ROS levels were significantly increased （P<0.01）， and the protein and mRNA expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin were significantly down-regulated （P<0.01）. As compared with the model group， the expression of CD31 was increased （P<0.05）， and α-SAM and Col-Ⅳ in the resveratrol group and the medium and high-dose Yishen Huoxue prescription groups were significantly decreased （P<0.01）. The ROS content was significantly decreased （P<0.01）， and the protein and mRNA expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin were up-regulated （P<0.01）， As compared with the resveratrol group， the protein expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin in the medium and low-dose Yishen Huoxue prescription groups were significantly different （P<0.01）. There was no significant difference in the mRNA expressions of CD31 and Ang-1/Tie-2 in the high-dose Yishen Huoxue prescription group， and no significant difference in the ROS level in the medium-dose Yishen Huoxue prescription group. ConclusionThe anti-RIF effect of Yishen Huoxue prescription may be related to promoting vascular endothelial repair， regulating mitochondrial ROS to reduce oxidative stress， protecting the integrity of renal endothelial structure， delaying cell apoptosis， and maintaining cell energy metabolism.

Objective:To investigate the relationship between the volume ratio of ischemic leukoaraiosis (LA) and cognitive level and arterial perfusion.Methods:Fifty-four patients, who was hospitalized in Dalian Central Hospital and diagnosed as LA clinically during the time of March to December in 2012, were selected to collect the information of the volume ratio of white matter disease, MoCa score and the average flow rate of carotid artery. The correlation between the volume ratio of white matter disease and MoCa score, cognitive impairment and the average flow rate of carotid artery were analyzed.Results:The volume ratio of LA lesions was negatively correlated with MOCA score ( r = -0.59, P<0.01); the volume ratio of LA lesions was negatively correlated with the mean flow rate of internal carotid artery ( r = -0.37, P<0.01). Quantity order of the area under receiver operating characteristic (ROC) curve of MoCA cognitive subgroup was as following: delayed memory (1.000)> visual space/executive function (0.970) = abstract force (0.970)> language ability (0.960)> attention (0.888). Conclusions:The larger the volume ratio of leukopathy in LA patients, the more serious the cognitive impairment, especially the cognitive impairment of impairment of memory delay, visual space/executive function, abstract ability and language ability.

Objective: To explore the effect of individualized nutrition intervention mode based on dysphagia screening in postoperative patients with cerebellopontine angle occupying lesion. Methods: By developing nurses training, selecting special screening and evaluation tools, developing screening methods and individualized nutrition intervention measures and meal spectrum, making screening and intervention flow chart, and starting to be implemented in postoperative patients with cerebellopontine angle occupying lesion in July 2017. Forty-six patients with cerebellopontine angle occupying lesion in the previous year were reviewed as the control group, who were given routine treatment and nursing; One year after implementation, Another 48 patients were set as the experimental group, and were given individualized nutritional care based on screening of dysphagia. Results: The incidence rate of dominant aspiration(0), pneumonia (4.17%, 2/48) and diarrhea (2.08%,1/48) in the experimental group was lower than 4.35% (2/46), 21.74% (10/46), 19.57% (9/46) in the control group, especially the difference of incidence rate of pneumonia and diarrhea was statistically significant (pneumonia: χ²=0.010, P=0.013; diarrhea: χ²=0.006, P=0.007). The retention rate of gastric tube in the experimental group (31.30%, 18/48) was lower than that in the control group (58.70%, 27/46), the difference was statistically significant (χ²=7.158, P=0.007). Average retention time of gastric tube in the experimental group (4.47±1.13) d was less than that in the control group (5.11±0.70) d, the difference was statistically significant (t=2.296, P=0,027). The hospitalization time in the experimental group (8.69±1.36) d were less than those in the control group (12.57±2.95) d, the difference was statistically significant (t=8.248, P=0,000). The nutritional status of 7 days after operation of the experimental group was better than that of the control group, the differenc e was statistically significant (albumin: t=4.888, P<0.01; prealbumin: t=5.188, P<0.01; hemoglobin: t=4.039, P<0.01). The knowledge and skills of swallowing of general nurses improved significantly after the work, in particular, the accuracy of screening tests for Wa Tian drinking water increased from 5/8 to 20/20. The difference was statistically significant (χ²=8.148, P=0.017). Conclusions Individualized nutrition intervention based on screening for dysphagia can improve the clinical outcome of patients, improve the comprehensive ability of nurses and achieve a win-win situation of nurse - patient.

OBJECTIVE To establish an modified model of osteonecrosis in the rat and observe the clinical, pathological and imaging manifestations dynamically. METHODS Healthy male SD rats were divided into 5 groups randomly, including the control group (N, 8 rats), and radiation groups (a, b, c and d, 6 rats each group). For radiation groups, the left mandible of each rat was irradiated at doses of 7.0 Gy for 5 fractions, other rats were sham irradiated, serving as control groups.7 days after irradiation, the left mandibular molars of all rats were extracted. The radiation groups rats were sacrificed at 7, 14, 21, 28 days after irradiation randomly, the 2 rats in control group were sacrificed respectively. All the rats' mandibles were taken and examined by clinical manifestation and Micro-CT and histology methods. The data was analyzed with SPSS 18.0 software package. RESULTS In clinical observation, ulcers were seen in the irradiated site at the 7th day, after then, alopecia, occlusion disorder, and pus discharged from buccal side were seen. Weight loss rightly after radiation and weight gain were seen at the 14th day. In pathological observation, marrow cavity changed first. Many adipose cell was first seen at the 7th day, and inflammations, necrosis, and fibrosis were found in medulla in the irradiated groups after that. Significant increment of empty lacunae and decrement of osteocytes were observed in all irradiated groups at the 7th day. Necrotic bone of the irradiated mandible was only found at the 28th day. Lack of new bone formation within the socket was seen in the Micro-CT three-dimensional at 28th day, and there are no more changes at the early-stage in this model. CONCLUSION An modified rat model of osteoradionecrosis was successfully established, which can shorten experimental period, and this model early stage and deserved to be further researched. Can be used to observe clinical, pathological and imaging magnification, which play a basic role in the protection in early stage and deserved to be further researched.

Objective To study the homology characteristics of clinicaly isolated and colonized linezolid(LZD)-resistant Enterococcus faecalis (E.faecalis) strains from a patient.Methods Ten E.faecalis strains (2 were isolated from urine specimens and 8 were from stool specimens) isolated from a patient with pulmonary infection were performed antimicrobial susceptibility testing, homology of E.faecalis was determined by pulsed-field gel electrophoresis (PFGE).Results Before and after patients received LZD therapy, 2 E.faecalis strains isolated form urine specimens were both resistant to LZD (MICs: 8 mg/mL, 16 mg/mL, respectively), among 8 strains from stool specimens (6 were isolated before therapy, and 2 were isolated after therapy), LZD susceptible, intermediate, and resistant strains were 4, 2, and 2 respectively(MICs: 0.25-12 mg/mL).10 strains of E.faecalis were homologous by PFGE typing.Conclusion In this case, the detection of E.faecalis from urinary tract and intestinal tract is homologous, which suggested that LZD-resistant Enterococcus may be colonized in vivo for a long time, and may be shift to cause bacterial infection.