Background: Lung adenocarcinoma (LUAD) is the major subtype of lung cancer and is associated with very high mortality. Emerging studies have shown that N6-methyladenosine (m6A)-related long non-coding (lnc) RNAs play crucial roles in tumor prognosis and the tumor immune microenvironment (TME). We aimed to explore the expression patterns of different m6A-related lncRNAs concerning patient prognosis and construct an m6A-related lncRNA prognostic model for LUAD.Methods: The prognostic value of m6A-related lncRNAs was investigated in LUAD samples from The Cancer Genome Atlas (TCGA). Potential prognostic m6A-related lncRNAs were selected by Pearson’s correlation and univariate Cox regression analysis. Patients were divided into clusters using principal component analysis and the m6A-related lncRNA prognostic signature was calculated using least absolute shrinkage and selection operator (LASSO) Cox regression analysis.Results: Based on 91 prognostic m6A-related lncRNAs, we identified two m6A-related-lncRNA pattern clusters with different overall survival (OS) and different TMEs. We subsequently verified our findings multidimensionally by constructing a 13 m6A-related lncRNA prognostic signature (m6A-LPS) to calculate the risk score, which was robust in different subgroups. The receiver operating characteristic (ROC) curves and concordance index demonstrated that m6A-LPS harbored a promising ability to predict OS in TCGA data set and independent GSE11969 cohort. The risk score was also related to OS, TME, and clinical stage, and the risk score calculated by our model was also identified as independent prognostic predictive factors for LUAD patients after adjustment for age, smoking, gender, and stage. Enrichment analysis indicated that malignancy and drug resistance-associated pathways were more common in cluster2 (LUAD-unfavorable m6A-LPS). Furthermore, the results indicated that the signaling pathway enriched by the target gene of 13 m6A-related lncRNAs may be associated with metastasis and progression of cancer according to current studies.Conclusion: The current results indicated that different m6A-related-lncRNA patterns could affect OS and TME in patients with LUAD, and the prognostic signature based on 13 m6A-related lncRNAs may help to predict the prognosis in LUAD patients.
Background Although immunotherapy has shown clinical activity in lung adenocarcinoma (LUAD), LUAD prognosis has been a perplexing problem. We aimed to construct an immune-related lncRNA pairs (IRLPs) score for LUAD and identify what immunosuppressor are appropriate for which group of people with LUAD. Methods Based on The Cancer Genome Atlas (TCGA)-LUAD cohort, IRLPs were identified to construct an IRLPs scoring system by Cox regression and validated in the Gene Expression Omnibus (GEO) dataset using log-rank test and the receiver operating characteristic curve (ROC). Next, we used spearman’s correlation analysis, t-test, signaling pathways analysis and gene mutation analysis to explore immune and molecular characteristics in different IRLP subgroups. The “pRRophetic” package was used to predict the sensitivity of immunosuppressant. Results The IRLPs score was constructed based on eight IRLPs calculated as 2.12 × (MIR31HG|RRN3P2) + 0.43 × (NKX2-1-AS1|AC083949.1) + 1.79 × (TMPO-AS1|LPP-AS2) + 1.60 × (TMPO-AS1|MGC32805) + 1.79 × (TMPO-AS1|PINK1-AS) + 0.65 × (SH3BP5-AS1|LINC01137) + 0.51 × (LINC01004|SH3PXD2A-AS1) + 0.62 × (LINC00339|AGAP2-AS1). Patients with a lower IRLPs risk score had a better overall survival (OS) (Log-rank test PTCGA train dataset < 0.001, PTCGA test dataset = 0.017, PGEO dataset = 0.027) and similar results were observed in the AUCs of TCGA dataset and GEO dataset (AUC TCGA train dataset = 0.777, AUC TCGA test dataset = 0.685, AUC TCGA total dataset = 0.733, AUC GEO dataset = 0.680). Immune score (Cor = -0.18893, P < 0.001), stoma score (Cor = -0.24804, P < 0.001), and microenvironment score (Cor = -0.22338, P < 0.001) were significantly decreased in the patients with the higher IRLP risk score. The gene set enrichment analysis found that high-risk group enriched in molecular changes in DNA and chromosomes signaling pathways, and in this group the tumor mutation burden (TMB) was higher than in the low-risk group (P = 0.0015). Immunosuppressor methotrexate sensitivity was higher in the high-risk group (P = 0.0052), whereas parthenolide (P < 0.001) and rapamycin (P = 0.013) sensitivity were lower in the high-risk group. Conclusions Our study established an IRLPs scoring system as a biomarker to help in the prognosis, the identification of molecular and immune characteristics, and the patient-tailored selection of the most suitable immunosuppressor for LUAD therapy.
Background: Approximately 50% of thymoma patients also show myasthenia gravis (MG), which is an autoimmune disease; however, the pathogenesis of MG-associated thymoma remains elusive. Our aim was to investigate immune-related lncRNA profiles of a set of candidate genes for better understanding of the molecular mechanism underlying the pathogenesis of thymoma with or without MG.Methods: Molecular profiles of thymoma with or without MG were downloaded from The Cancer Genome Atlas, and Pearson’s correlation analysis was performed to identify immune-related lncRNAs. T test was used to examine the differential expression and differential methylation between thymoma patients with or without MG. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to predict the function of target genes of immune-related lncRNAs.Results: Analyses of the 87 thymoma samples with complete MG information revealed that 205 mRNAs and 56 lncRNAs showed up-regulated expression in thymoma with MG patients, while 458 mRNAs and 84 lncRNAs showed down-regulated expression. The methylation level of three immune-related lncRNAs (AP000787.1, AC004943.1, WT1-AS, FOXG1-AS1) was significantly decreased in thymoma tissues, and the methylation level of these immune-related lncRNAs (WT1-AS: Cor = 0.368, p < 0.001; FOXG1-AS1: Cor = 0.288, p < 0.01; AC004943.1: Cor = -0.236, p < 0.05) correlated with their expression. GO and KEGG pathway analysis revealed that targets of the immune-related lncRNA FOXG1-AS1 were enriched in small GTPase binding and herpes simplex virus 1 infection. Transcription coregulator activity and cell cycle were the most enriched pathways for targets of lncRNA AC004943.1. LncRNA WT1-AS targets were most enriched in actin binding and axon guidance.Conclusion: Our results revealed the immune-related molecular profiling of thymoma with MG and without MG and identified key pathways involved in the underlying molecular mechanism of thymoma-related MG. These findings provide insights for further research of potential markers for thymoma-related MG.
This study showed CLS provides a valid option for the treatment of idiopathic LR. The efficacy of CLS can be long-lasting, and CLS can be repeated if LR recurs. Targeting at gray rami communicans, rather than the sympathetic trunk, is comparably effective and safer for sympathetic interruption.
Background and ObjectivesAnxiety plays an important role in psychology. An exploration of anxiety and its associated reactions may provide insight into measures for addressing mental health problems caused by the coronavirus disease 2019 (COVID-19) pandemic. Data from this study provide potential correlational responses to anxiety.MethodsA cross-sectional study using data collected via an online self-reported questionnaire was conducted in Japan during the COVID-19 pandemic. Using the State-Trait Anxiety Inventory (STAI-6), we assessed anxiety levels and explored the relationship between anxiety STAI-6 score, sources of COVID-19 information, the influences of COVID-19, social anxiety symptoms, discrimination, and evaluation of the government.ResultsA total of 4,127 participants were included in the analysis. The level of anxiety was not equally distributed across the general population with respect to age, gender, educational level, occupation, income, presence of underlying disease, and location (p < 0.05). The number of sources of information on COVID-19 had a positive correlation with the STAI-6 score (Spearman’s rho = 0.176, p < 0.001). The influence of the pandemic was correlated with moderate–severe anxiety. A high level of anxiety added to social anxiety (Spearman’s rho = 0.04, p < 0.05) and discriminatory behavior (Spearman’s rho = 0.11, p < 0.01). Being female (Estimate = 0.926) and from a non-emergency area (Estimate = −0.308) was related to higher STAI scores, and higher education (Estimate = −0.305), and income (Estimate = −0.168) decreased the STAI score. The respondents who had a lower evaluative score of the preventive activities undertaken by the national and local governments had higher STAI-6 scores.ConclusionOur findings provide statistical evidence for the associated reaction of anxiety and that anxiety reactions may vary in predictable ways. Further studies should focus on the strategic interventions that may decrease the associated responses to anxiety, to address mental health issues due to the pandemic.
Background Heterosexual contact is the primary mode of HIV transmission in China and commercial sex is thought to play a crucial role in China’s epidemic. Female sex works (FSWs) in China tend to be either brothel-based (BSWs) or street-based (SSWs), but few studies have investigated the differences between these important segments of this difficult-to-reach, high-risk population. Our aim was to explore these differences. Methods A cross-sectional survey was conducted in Yunnan Province of China in partnership with a local FSW-friendly non-governmental organization. Face-to-face interviews using a structured questionnaire were conducted to collect data on socio-demographic characteristics, sex work history, sexual behaviours, HIV/STI-related knowledge, HIV testing history, and healthcare services uptake. Blood samples were taken for HIV and syphilis testing, and urine samples for gonorrhea and chlamydia testing. Descriptive statistics were used to evaluate differences between SSWs and BSWs. Results A total of 185 BSWs and 129 SSWs were included in the study. SSWs were older and less educated, had more dependents and more clients, accessed fewer healthcare services, and had higher prevalence of HIV/STIs. SSWs also had similar but higher rates of consistent condom use with clients.Conclusions Our study provides evidence that confirms the disproportionately high vulnerability of SSWs to HIV and other STIs, underscoring the urgent need for the Chinese health and public health sectors to prioritize outreach to SSWs. Awareness and educational programs, condom distribution, testing and health check-ups should be included in a comprehensive strategy for HIV/STI prevention in this high-risk population.
Background and purpose Health-related quality of life (HRQoL) is a key aspect of care for cancer survivors that can be improved by physical activity. Our aim was to explore the relationship between physical activity and time to deterioration (TTD) of the HRQoL in patients with lung adenocarcinoma (LUAD). Methods We conducted a hospital-based prospective study. The International Physical Activity Questionnaire long-form (IPAQ-L) was used to investigate the pre-treatment physical activity levels, and the EORTC Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) were used to assess HRQoL at baseline and during follow-up. The QoLR package was used to calculate the HRQoL scores and determine TTD events (minimal clinically important difference=5 points). The effect of physical activity on the HRQoL was assessed using Cox regression analysis. Results For EORTC QLQ-C30, TTD events of physical functioning (PF) and dyspnea (DY) in functional scales and symptom scales were the most common during follow-up. Pre-treatment physical activity was found to significantly delay TTD of insomnia (HR=0.635, 95%CI: 0.437–0.922, P=0.017) and diarrhea (HR=0.475, 95%CI: 0.291–0.774, P=0.003). For EORTC QLQ-LC13 scales, deterioration of dyspnea (LC-DY) was the most common event. Physical activity was found to delay the TTD of dyspnea (HR=0.654, 95%CI: 0.474–0.903, P=0.010), sore mouth (HR=0.457, 95%CI: 0.244–0.856, P=0.015), and dysphagia (HR=0.315, 95%CI: 0.172–0.580, P<0.001). Conclusions Pre-treatment physical activity of LUAD patients may delay the TTD of multiple HRQoL indicators in EORTC QLQ-C30 and EORTC QLQ-LC13. Implication for Cancer Survivors Health-related quality of life (HRQoL) is a key aspect of care for cancer survivors (someone who is living with or beyond cancer), that can be improved by physical activity. Our aim was to explore the relationship between physical activity and time to deterioration (TTD) of the HRQoL in patients with lung adenocarcinoma (LUAD).
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