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*

OBJECTIVE To analyze the MSCT and MRI imaging manifestations of patients with duplication of the internal auditory canal(DIAC),improve understanding of the deformity,to provide preoperative basis for cochlear implantation.METHODS Retrospective observation of 20 cases(24 ears)of DIAC inner ear multi-spiral CT(MSCT)and MRI data,measurement and analysis of the width of the internal auditory canal(IAC)and cochlear nerve canal in the lesion group and the control group.RESULTS All DIACs had stenosis of the IAC cambined with other temporal bone malformations.MSCT shows that the 21 ears IAC,while MRI hydrography shows the 16 ears IAC divided into double tubes by bone.MRI hydrography shows a slender vestibulocochlear nerve.There were statistically significant differences(P<0.001)in the width of IAC and cochlear nerve canal between the lesion group and the control group.Six cases(8 ears)had varying degrees of hearing recovery after cochlear implant surgery.CONCLUSION DIAC shows stenosis of the IAC;The bone septa shown on MSCT are its characteristic fertures;MRI hydrography shows underdeveloped vestibular and cochlear nerves;The combination of two imaging examination methods can provide objective reference for the diagnosis of this disease and artificial auditory implantation.

Pancreatic cancer induced by mutation KRAS exhibited a higher risk of incidence, recurrence and mortality. C-Myc is downstream of KRAS and can be involved in the regulation of multiple oncogenic pathways and signaling pathways in pancreatic cancer. Over expressing of C-Myc promotes glycolysis and glutamine uptake in pancreatic cancer cells, promotes cell metabolism and proliferation, is an important factor driving the progress and maintenance of pancreatic cancer, and is related to chemotherapy and immunotherapy drug resistance. C-Myc also interacts with cell cyclin-dependent kinase(CDK) and non-coding RNA to regulate the proliferation, development and metastasis of pancreatic cancer. Therefore, targeting C-Myc was regarded as an effective strategy for the treatment of pancreatic cancer. The activation of C-Myc depends on heterodimerization with its partner MAX and thereby paly a role through binding to the canonical E-Box sequence 5’-CACGTG-3’. Researches showed direct targeting of C-Myc can inhibit the growth of pancreatic carcinoma,such as promoting the degradation of C-Myc, inhibiting the binding of C-Myc/MAX and blocking the binding of C-Myc/MAX to E-box. However, direct targeting has been proved challenging because of its special protein structure. Indirect targeting of C-Myc provided a new strategy for the treatment of pancreatic cancer. C-Myc can be indirected targeting through inhibiting transcription and translation of C-Myc, C-Myc-MAX heterodimerization and promote the ubiquitination and degradation of C-Myc, thus affects the occurrence, development and metastasis of pancreatic cancer.

Objective:To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma.Methods:2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival.Results:A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P ?

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

Objective:To investigate the epidemiological and clinical characteristics of human parainfluenza viruses (HPIVs) infection among hospitalized children with community-acquired pneumonia (CAP) in China, and provide basic data for diagnosis, treatment and prevention of HPIVs infection.Methods:From November 2014 to February 2020, 5 448 hospitalized children with CAP were enrolled in 14 hospitals in 11 provinces and municipalities directly under the Central Government in southern China and northern China. Nasopharyngeal aspirates or throat swabs were collected, and the nucleic acids of 18 types respiratory viruses including HPIV1-4 were screened by suspension array technology. Demographic data and clinical information were collected for statistical analysis.Results:The total detection rate of HPIVs in 5 448 children with CAP was 8.83% (481/5 448), and the detection rate in males was higher than that in females (62.79% vs. 37.21%; χ2=0.000, P=0.992). The detection rate of HPIVs in 1~< 3 years age group was higher than that in other age groups, and the difference was statistically significant ( χ2=61.893, P<0.001). The detection rate of HPIVs in the northern region was higher than that in the southern region (9.02% vs 8.65%), but the difference was not statistically significant ( χ2=0.239, P=0.625). The prevalence of HPIV1-4 in northern and southern China was not completely same. HPIV1 was mainly prevalent in autumn in both northern and southern regions. HPIV2 was prevalent in summer in northern China, and the detection rate was low in southern China. HPIV3 reached its peak in both spring and summer in both northern and southern China, but its duration was longer in southern China than in northern China. HPIV4 is mainly popular in autumn in both southern China and northern China. Among 481 children infected with HPIVs, 58.42% (281/481) were infected with HPIV alone, and the main clinical manifestations were cough (90.75%) and fever (68.68%). Out of the HPIV-positive cases, 42.62% (205/481) were co-infected with another type of HPIV or a different virus, while 11.43% (55/481) had co-infections with two or more different viruses. HPIV3 was the most common type of co-infection with other viruses. HPIV3 infection accounted for the largest proportion (76.80%) in 47 HPIVs-positive children with severe pneumonia. Conclusions:HPIVs is one of the most important pathogens causing CAP in children in China, and children under 3 years of age are the main populations of HPIVs infection. The prevalence characteristics of all types of HPIVs in children in the north and south are not completely same. HPIV3 is the dominant type of HPIV infections and causes more severe diseases.

Objective To study the local efficacy of ultrasound-guided interstitial implantation of radioactive 125I seeds in the treatment of hepatic tumors at dangerous sites.Methods A retrospective study was conducted on 39 patients who were admitted into the First Medical Center,PLA General Hospital from November 2011 to January 2018.There were 23 males and 16 females.A three-dimensional planning before 125I seed implantation was performed for all these patients using the treatment planning system (TPS).The implantation was performed under ultrasound guidance.Liver CT scan was performed in all the patients after implantation to evaluate the actual distribution of the seeds in the tumors.Follow-up was performed at 2,4,6,9 and 12 months after implantation,respectively,to evaluate using complete response (CR),partial response (PR),steady disease (SD),progressive disease (PD) and local control rates (LCR).Results Implantation was successfully performed in all the 39 patients.CT scan showed that 5 patients (12.8％)required additional implantation.Follow-up imaging after implantation showed local control of the lesions was good.The rates of CR,PR,SD and LCR were 2.6％ (1/39),28.2％ (11/39),66.7％ (26/39) and 97.4％ (38/39),respectively.One patient (2.6％,1/39) showed local progressive disease.The LCR reached 97.4％ (38/39) at 12 months of follow-up.Conclusion Ultrasound-guided radioactive 125I seed implantation was efficacious in the treatment of hepatic tumors at dangerous sites.

Objective To investigate the status of self-management of elderly patients with chronic heart failure (CHF) in Xinjiang Region,and to explore the effects of different demographic factors on self-management.Methods A total of 704 patients with chronic heart failure were randomly selected from Urumqi,Kashgar,Khotan,Changji,Shihezi,Yili Hazakh in Xinjiang Uygur Autonomous Region via convenience sampling method and were investigated using heart failure self-management scale.Results The total score of self-management of chronic heart failure elderly patients was(47.6±11.1) and scoring rate was 59.5％.There were statistically significant differences(P＜0.01) in self-management score among patients with different ethnicity,religion,self-care ability,per capita income.The influencing factors of self-management were self-care ability,NYHA class and per capita monthly income(P＜0.05).Conclusion The overall level of self-management of elderly patients with chronic heart failure in Xinjiang Region is low,and self-management is affected by self-care ability,NYHA class and per capita monthly income.Tailored culture-based education should be provided to improve patients' self-management.

Objective To explore the relationship between the polymorphism of integrin-metalloproteinase-33 (ADAM33) gene and bronchial asthma. Methods Subjects were selected from the Department of Respiratory Medicine in our department from June 2015 to December 2016 in the treatment of 120 cases of asthma patients as the observation group, the same period into our hospital physical examination of 120 healthy children as the control group. The patients were enrolled in the upper extremity elbow vein and extracted DNA, followed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. The frequency of T2 genotype distribution and the frequency distribution of T2 locus and the relative risk of asthma were compared according to Hardy-Weinberg equilibrium law. Results The frequency of A gene in the T2 allele of the subject was significantly higher than that of the control group. The frequency of A gene in the T2 allele was significantly higher than that in the control group (P<0.05) There was significant difference between the two groups (χ2=8.09, P=0.00), and the increase of A allele was the risk factor of asthma (OR=2.32); the observation group T2 gene AG (χ2=4.21, P=0.04), and the increase of AG allele was the risk factor of asthma. The frequency of asthma was significantly higher than that of control group (OR=1.89). Conclusion ADAM33 gene T2 locus polymorphism is significantly associated with bronchial asthma, which can significantly increase the risk of bronchial asthma.

Objective To examine the distribution of systemic inflammation and risk factors of cardiovascular disease (CVD) in patients with psoriatic arthritis (PsA) by comparing with healthy controls.Methods Forty PsA patients and 44 controls were recruited into this cross-sectional study.We evaluated the disease activity and severity [erythrocyte sedimentation rate (ESR),C reactive protein(CRP) and Disease Activity Score (DAS)28],functional ability in patients with predominant axial involvement [Bath AS disease activity index (BASDAI) and Bath AS functional index (BASH)],traditional CVD risk factors and inflammation between these two groups of patients.Then,we compared risk factors for CVD between 40 consecutive PsA patients and 44 controls,adjusted for body mass index (BMI).The frequencies were compared using chi-square tests for categorical variables.Student's t-tests or Mann-Whitney U-tests were used forcontinuous variables where appropriate.Association between the traditionaland metabolic risk factors and the hs-CRP level were assessed using Spearman correlations.Finally,we also assessed the role of inflammation on the CVD risk factor by using a BMI and hs-CRP-adjusted model.Results The BMI of PsA patients was significantly higher than that of the controls.After adjusting for the BMI,PsA patients had a higher prevalence of hypertension (OR=5.615,95％CI 1.844-17.099) and diabetes mellitus (OR=10.655,95％CI 1.150-98.683) than the controls.PsA patients had significantly increased systolic and diastolic blood pressures [(SBP) and (DBP)],total cholesterol (TC)/high density lipoprotein cholesterol (HDL),insulin resistance,inflammatory markers (hsCRP,white cell count and platelet) and decreased HDL compared to the controls.As excepted,the hsCRP level [4.0 (2.1-13.9) vs 1.7 (1.3-2.2)],platelet and white cell counts were significantly increased in the PsA group reflecting underlying inflammation.Further adjustment for hsCRP level rendered the differences in the prevalence of hypertension (OR=3.544,95％CI 1.151-10.914);but the DBP,HDL and sugar levels were non-significantly different between the two groups,while the differences in other parameters were significant.Conclusion The data support the hypothesis that PsA may be associated with hypertension,obesity and dyslipidemia because of the shared inflammation pathway.