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*

Genomic imprinting refers to the phenomenon of differential expression of two alleles due to their different parental origins. Genes that produce genomic imprinting are usually called imprinted genes. The genetic effect caused by the presence of imprinted genes is called parent-of-origin effect. Parent-of-origin effect and genomic imprinting play important roles in the pathophysiological mechanism and occurrence and development of cardio-metabolic diseases. In-depth exploration of the law and potential roles of imprinted genes and parent-of-origin effects will help to better understand the mechanism of cardio-metabolic diseases, and also provide important theoretical basis for the precise treatment of diseases related to imprinted genes.

Objective:To explore the spousal correlations of total cholesterol(TC),total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and to investigate the reasons behind these spousal correlations.Methods:Participants and data were from the baseline survey of family-based cohort studies in Fangshan,Beijing and Tulou,Fujian.The ori-gin of spousal correlations were explored from perspectives of convergence,assortative mating,social ho-mogamy.Pearson's correlation and generalized linear models(GLM)were used to estimate the spousal correlation.Convergence was assessed by Pearson's correlation between the phenotypic differences be-tween couples and the duration of marriage,with GLM used for further validation.Pearson's correlation of genetic risk scores(GRS)and couple-specific Mendelian randomization(MR)were calculated to assess the genetic correlation and possible causal relationships between spouses.Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment,couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences.Results:In the study,342 couples(287 couples from Fangshan and 55 couples from Fujian)were included,with the average age of(64.91±8.76)years.Spousal correlations of TC,TG,HDL-C,and LDL-C showed statistically significant associations both before and after adjusting for covariates,with effect sizes of 0.229(95％CI:0.125-0.327),0.257(95％CI:0.155-0.354),0.179(95％CI:0.074-0.280),and 0.181(95％CI:0.076-0.282).For convergence,for each additional year of marriage,ΔTC increased by 0.016 mmol/L(95％CI:0.001-0.033 mmol/L),and ΔLDL-C increased by 0.017 mmol/L(95％CI:0.002-0.031 mmol/L).For assortative mating,GRS correlations and results of couple specific MR didn't show any statistical significance.For social homogamy,no differences in GRS or assortative mating were found between subgroups stratified by education attainment.Conclusion:The blood lipid in participants exhibit spousal phenotypic correlations,however,no effects of convergence,assortative mating or social homogamy were observed.More independent studies with larger sample sizes are warranted to further validate these findings in the future.

Atherosclerosis is recognized as an inflammatory disease,and its development is regulated by multiple fac-tors,particularly dyslipidemia.Peroxisome proliferator-activated receptor(PPAR)regulate the expression of genes that are involved in lipid metabolism and inflammation;and they have three subfamily members including PPARα,PPARβ,and PPARγ.However,synthetic PPAR agonists exhibit ambiguous effects in atherosclerotic therapy and induce various side effects.Notably,recent studies demonstrate that traditional Chinese medicine(TCM)alleviate atherosclerotic cardiovascular diseases via suppressing hyperlipidemia and inflammation through regulation of PPAR signaling pathway.This article pri-marily reviews the regulatory effects of TCM on PPAR and their therapeutic effects on atherosclerosis,provides valuable in-formation for pharmacologists that are interested in searching for effective herbal prescriptions for atherosclerosis therapy and for clinicians that are interested in prevention and treatment of atherosclerotic cardiovascular diseases using TCM.

Objective:To explore the spousal correlations of total cholesterol(TC),total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and to investigate the reasons behind these spousal correlations.Methods:Participants and data were from the baseline survey of family-based cohort studies in Fangshan,Beijing and Tulou,Fujian.The ori-gin of spousal correlations were explored from perspectives of convergence,assortative mating,social ho-mogamy.Pearson's correlation and generalized linear models(GLM)were used to estimate the spousal correlation.Convergence was assessed by Pearson's correlation between the phenotypic differences be-tween couples and the duration of marriage,with GLM used for further validation.Pearson's correlation of genetic risk scores(GRS)and couple-specific Mendelian randomization(MR)were calculated to assess the genetic correlation and possible causal relationships between spouses.Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment,couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences.Results:In the study,342 couples(287 couples from Fangshan and 55 couples from Fujian)were included,with the average age of(64.91±8.76)years.Spousal correlations of TC,TG,HDL-C,and LDL-C showed statistically significant associations both before and after adjusting for covariates,with effect sizes of 0.229(95％CI:0.125-0.327),0.257(95％CI:0.155-0.354),0.179(95％CI:0.074-0.280),and 0.181(95％CI:0.076-0.282).For convergence,for each additional year of marriage,ΔTC increased by 0.016 mmol/L(95％CI:0.001-0.033 mmol/L),and ΔLDL-C increased by 0.017 mmol/L(95％CI:0.002-0.031 mmol/L).For assortative mating,GRS correlations and results of couple specific MR didn't show any statistical significance.For social homogamy,no differences in GRS or assortative mating were found between subgroups stratified by education attainment.Conclusion:The blood lipid in participants exhibit spousal phenotypic correlations,however,no effects of convergence,assortative mating or social homogamy were observed.More independent studies with larger sample sizes are warranted to further validate these findings in the future.

Genomic imprinting refers to the phenomenon of differential expression of two alleles due to their different parental origins. Genes that produce genomic imprinting are usually called imprinted genes. The genetic effect caused by the presence of imprinted genes is called parent-of-origin effect. Parent-of-origin effect and genomic imprinting play important roles in the pathophysiological mechanism and occurrence and development of cardio-metabolic diseases. In-depth exploration of the law and potential roles of imprinted genes and parent-of-origin effects will help to better understand the mechanism of cardio-metabolic diseases, and also provide important theoretical basis for the precise treatment of diseases related to imprinted genes.

Atherosclerosis is recognized as an inflammatory disease,and its development is regulated by multiple fac-tors,particularly dyslipidemia.Peroxisome proliferator-activated receptor(PPAR)regulate the expression of genes that are involved in lipid metabolism and inflammation;and they have three subfamily members including PPARα,PPARβ,and PPARγ.However,synthetic PPAR agonists exhibit ambiguous effects in atherosclerotic therapy and induce various side effects.Notably,recent studies demonstrate that traditional Chinese medicine(TCM)alleviate atherosclerotic cardiovascular diseases via suppressing hyperlipidemia and inflammation through regulation of PPAR signaling pathway.This article pri-marily reviews the regulatory effects of TCM on PPAR and their therapeutic effects on atherosclerosis,provides valuable in-formation for pharmacologists that are interested in searching for effective herbal prescriptions for atherosclerosis therapy and for clinicians that are interested in prevention and treatment of atherosclerotic cardiovascular diseases using TCM.

Objective:To evaluate the value of 18F-FDG PET/CT for preoperative localization of epileptogenic foci in refractory epilepsy patients with negative MRI. Methods:Clinical data (550 lobes) of 55 epilepsy patients (38 males, 17 females, age (20.0±8.1) years) with negative MRI who underwent preoperative 18F-FDG PET/CT-MRI between January 2014 and June 2020 at the First Affiliated Hospital of Jinan University were retrospectively analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT, video electroencephalogram (VEEG), PET/CT+ VEEG and PET/CT-VEEG for localizing epileptogenic foci were calculated using stereoelectroencephalography (SEEG) and the outcomes of at least 1 year of postoperative follow-up as reference standards. χ2 test was used to compare the efficiencies of different examination modalities for unilobar, multilobar and all patients. Results:The correct lateralization rate of epileptogenic foci was 92.6%(25/27) using PET/CT. The sensitivity, specificity, accuracy, PPV and NPV of PET/CT for localization of epileptogenic foci were 65.1%(54/83), 77.9%(364/467), 76.0%(418/550), 34.4%(54/157) and 92.6%(364/393), respectively. The sensitivities of PET/CT-VEEG for localization of epileptogenic foci in all patients and patients with multilobar epilepsy were higher than those of VEEG alone (75.9%(63/83) vs 45.8%(38/83), 68.6%(35/51) vs 31.4%(16/51); χ2 values: 15.80, 14.16, both P<0.001). The specificities of PET/CT+ VEEG for localization of epileptogenic foci in all patients and patients with unilobar epilepsy were higher than those of VEEG alone (97.6%(456/467) vs 94.6%(442/467), 97.9%(282/288) vs 94.1%(271/288); χ2 values: 5.66, 5.48; P values: 0.017, 0.019). The sensitivity of PET/CT-VEEG (PET/CT and VEEG concordance) for localization of epileptogenic foci was higher than that of PET/CT+ VEEG (PET/CT and VEEG discordance) (8/9 vs 28.4%(21/74); χ2=10.40, P=0.001), and its specificity and accuracy were higher than those of PET/CT-VEEG (PET/CT and VEEG discordance) (93.4%(57/61) vs 71.7%(291/406), 92.9%(65/70) vs 72.1%(346/480); χ2 values: 13.23, 13.96; both P<0.001). Conclusions:18F-FDG PET/CT can localize and lateralize epileptogenic foci in patients with negative MRI. The combination of 18F-FDG PET/CT and VEEG improves the sensitivity, specificity, and accuracy for epileptogenic foci detection. 18F-FDG PET/CT is more accurate in detecting epileptogenic foci when it is concordant with VEEG.

Objective:To predict the short-term postoperative recurrence status of patients with refractory temporal lobe epilepsy (TLE) by analyzing preoperative 18F-FDG PET images and patients′ clinical characteristics based on deep residual neural network (ResNet). Methods:Retrospective analysis was conducted on preoperative 18F-FDG PET images and clinical data of 220 patients with refractory TLE (132 males and 88 females, age 23.0(20.0, 30.2) years)) in the First Affiliated Hospital of Jinan University between January 2014 and June 2020. ResNet was used to perform high-throughput feature extraction on preprocessed PET images and clinical features, and to perform a postoperative recurrence prediction task for differentiating patients with TLE. The predictive performance of ResNet model was evaluated by ROC curve analysis, and the AUC was compared with that of classical Cox proportional risk model using Delong test. Results:Based on PET images combined with clinical feature training, AUCs of the ResNet in predicting 12-, 24-, and 36-month postoperative recurrence were 0.895±0.073, 0.861±0.058 and 0.754±0.111, respectively, which were 0.717±0.093, 0.697±0.081 and 0.645±0.087 for Cox proportional hazards model respectively ( z values: -3.00, -2.98, -1.09, P values: 0.011, 0.018, 0.310). The ResNet showed best predictive effect for recurrence events within 12 months after surgery. Conclusion:The ResNet model is expected to be used in clinical practice for postoperative follow-up of patients with TLE, helping for risk stratification and individualized management of postoperative patients.

Objective This study aimed to explore the relationships between residential greenness and cardiometabolic risk factors among rural adults in Xinjiang Uygur Autonomous Region(Xinjiang)and thus provide a theoretical basis and data support for improving the health of residents in this region. Methods We recruited 9,723 adult rural residents from the 51st Regiment of the Third Division of the Xinjiang Production and Construction Corps in September 2016.The normalized difference vegetation index(NDVI)was used to estimate residential greenness.The generalized linear mixed model(GLMM)was used to examine the association between residential greenness and cardiometabolic risk factors. Results Higher residential greenness was associated with lower cardiometabolic risk factor prevalence.After adjustments were made for age,sex,education,and marital status,for each interquartile range(IQR)increase of NDVI500-m,the risk of hypertension was reduced by 10.3%(OR=0.897,95%CI=0.836-0.962),the risk of obesity by 20.5%(OR=0.795,95%CI=0.695-0.910),the risk of type 2 diabetes by 15.1%(OR=0.849,95%CI=0.740-0.974),and the risk of dyslipidemia by 10.5%(OR=0.895,95%CI=0.825-0.971).Risk factor aggregation was reduced by 20.4%(OR=0.796,95%CI=0.716-0.885)for the same.Stratified analysis showed that NDVI500-m was associated more strongly with hypertension,dyslipidemia,and risk factor aggregation among male participants.The association of NDVI500-m with type 2 diabetes was stronger among participants with a higher education level.PM10 and physical activity mediated 1.9%-9.2%of the associations between NDVI500-m and obesity,dyslipidemia,and risk factor aggregation. Conclusion Higher residential greenness has a protective effect against cardiometabolic risk factors among rural residents in Xinjiang.Increasing the area of green space around residences is an effective measure to reduce the burden of cardiometabolic-related diseases among rural residents in Xinjiang.