Background: Dysregulation of RNA guanine-7 methyltransferase (RNMT) plays a crucial role in the tumor progression and immune responses. However, the detailed role of RNMT in pan-cancer is still unknown. Methods: Bulk transcriptomic data of pan-cancer were obtained from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases. Single-cell transcriptomic and proteomics data of lung squamous cell carcinoma (LUSC) were analyzed in the Tumor Immune Single-cell Hub 2 (TISCH2) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, respectively. The correlation between RNMT expression and cancer prognosis was analyzed by Cox proportional hazards regression and Kaplan-Meier analyses. The correlation of RNMT expression with common immunoregulators, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methyltransferase (DNMT) was analyzed. Additionally, the correlation between RNMT expression and immune infiltration level was evaluated. A total of 1287 machine learning combinations were used to construct prognostic models for LUSC. qRT-PCR and Western blot were used to validate the bioinformatics findings of RNMT upregulation in LUSC. Results: RNMT was widely expressed across different cancers, with significant correlation to prognosis in cancers such as kidney chromophobe (KICH) (p = 0.0033, HR = 7.12), liver hepatocellular carcinoma (LIHC) (p = 0.01, HR = 1.41), and others. Notably, RNMT participates in the regulation of the tumor microenvironment. RNMT expression positively correlated with immune cell expression (Spearman's rank correlation, p < 0.05). Moreover, RNMT expression was strongly associated with immunoregulators, TMB, MSI, MMR, and DNMT in most cancer types. Notably, RNMT expression displayed excellent prognostic and immunological performance in LUSC. The expression of RNMT was mainly enriched in B cells of LUSC tissues. qRT-PCR and Western blot verified the high expression of RNMT in LUSC. Conclusion: RNMT expression widely correlated with prognosis and immune infiltration in various tumors, especially LUSC. The RNMT detection may provide a new idea for future tumor immune studies and treatment strategies.

As the main pathological basis for the development of cardiovascular and cerebrovascular diseases, atherosclerosis (AS) seriously affects human health. The key targets of biological information analysis of AS can help exploit therapeutic targets. The expression data of early and progressive atherosclerotic tissues were downloaded from the Gene Expression Omnibus (GEO) database. Based on GSE28829 and GSE120521, 74 key genes were obtained through differential expression analysis and weighted correlation network analysis (WGCNA) analysis, which were mainly enriched in the regulating of inflammatory response, chemokine signalling pathway, apoptosis, lipid and AS, Toll-like receptor signalling pathway and so on according to the results of the enrichment analysis. Cytoscape software was applied to screen four pivotal genes (TYROBP, ITGB2, ITGAM and TLR2) based on PPI. The results of the correlation analysis showed that the expression level of pivotal genes was positively related to macrophages M0, and was negatively related to T cells follicular helper. In addition, the expression of ITGB2 was positively related to Tregs. In this study, bioinformatics was applied to screen pivotal genes affecting the progress of AS, which were significantly related to immune-related biological functions and signal pathways of atherosclerotic tissues and the infiltration level of immune cells. Therefore, pivotal genes were expected to become therapeutic targets for AS.

Background: Whether individuals with non-obstructive spirometry-defined small airway dysfunction (SAD) have impaired exercise capacity is unclear, particularly in never-smokers. This study clarifies the degree of impaired exercise capacity and its potential cause in individuals with non-obstructive SAD. Methods: This community-based, multiyear cross-sectional study analyzed data collected in Guangdong, China from 2012-2019 by the National Science and Technology Support Plan Program. Measurements of exercise capacity [peak work rate and peak oxygen uptake ((V)over dotO(2peak))] in participants with non-obstructive spirometry-defined SAD (n=157) were compared with those in controls (n=85) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) I patients (n=239). Subgroup analyses were performed by smoking status. Results: The risk of impaired exercise capacity was significantly higher in participants with non-obstructive SAD [(V)over dotO(2peak) <84%predicted, adjusted odds ratio (aOR) =2.53; 95% confidence interval (CI): 1.42-4.52] than in controls but was not significantly different from that in GOLD I patients. Results were consistent within subgroups of smoking status (ever-smokers: non-obstructive SAD vs. controls, aOR =2.44; 95% CI: 1.08-5.51; never-smokers: non-obstructive SAD vs. controls, aOR =2.38, 95% CI: 1.02-5.58). Participants with non-obstructive SAD had a significantly lower peak work rate (beta=-10.5; 95% CI: -16.3 to -4.7) and (V)over dotO(2peak) (%predicted, beta=-4.0; 95% CI: -7.7 to -0.2) and tended to have higher ventilatory equivalents for carbon dioxide at the ventilatory threshold ((V)over dot(E)/(V)over dotCO(2AT), beta=1.1; 95% CI: -0.1 to 2.3) when compared with controls. Both peak work rate and (V)over dot O-2peak were negatively correlated with (V)over dot(E)/(V)over dotCO(2AT). Conclusions: Although not meeting the current criteria for chronic obstructive pulmonary disease, individuals with non-obstructive SAD have impaired exercise capacity that may be associated with ventilatory inefficiency regardless of smoking status.

[目的]  通过生物信息学方法探讨 METTL16在泛癌中的诊断价值及肿瘤预后评估的作用。 [方法]  从多个相关数据库中获取各个肿瘤及正常组织中的基因数据，分析了METTL16在不同癌症中的表达的表达水平，其中包括癌症细胞系百科全书    （CCLE）、癌症基因组图谱（TCGA）和基因型-组织表达项目（GTEx）。采用Cox回归分析和Kaplan-Meier分析来评估METTL16表达水平高低与肿瘤预后之间的关系。使用肿瘤免疫评估资源 (TIMER) 来评估METTL16与癌症中的免疫细胞浸润的相关性。同时，还分别分析了METTL16的表达水平与常见的免疫调节因子、DNA甲基转移酶（DNMTs）、错配修复（MMRs）、微卫星不稳定性（MSI）和肿瘤突变负荷（TMB）之间的关系。此外，通过基因集富集分析 (GSEA) 来识别癌症中的关键通路。 [结果]  METTL16在多种癌症中异常表达，生存分析表明其表达水平与许多癌症患者的临床预后相关。METTL16 的表达水平与结肠癌（COAD）、肾透明细胞癌（KIRC）、肝癌（LIHC） 中的的六种免疫浸润细胞（B细胞、CD4 + T细胞、CD8 + T细胞、树突状细胞、巨噬细胞和中性粒细胞）的表达水平呈正相关。此外，METTL16表达与多种癌症中的免疫检查点基因表达、MMR、DNA 甲基转移酶水平、TMB 和 MSI 显着相关。同时，GSEA 还揭示了METTL16参与了肿瘤和免疫相关信号通路的调控。 [结论]  METTL16与肿瘤预后和肿瘤免疫浸润密切相关，并在多种肿瘤的发生发展中起着重要作用。METTL16可能成为一种很有前途的各种肿瘤预后生物标志物，并为未来的肿瘤免疫研究和治疗策略提供新的思路。

Background: RNA guanine-7 methyltransferase (RNMT) is one of the main regulators of N7-methylguanosine, and the deregulation of RNMT correlated with tumor development and immune metabolism. However, the specific function of RNMT in pan-cancer remains unclear. Methods: RNMT expression in different cancers was analyzed using multiple databases, including Cancer Cell Line Encyclopedia (CCLE), Genotype-Tissue Expression Project (GTEx), and The Cancer Genome Atlas (TCGA). Cox regression analysis and Kaplan-Meier analysis were used to estimate the correlation of RNMT expression to prognosis. The data was also used to research the relationship between RNMT expression and common immunoregulators, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methyltransferase (DNMT). Additionally, the cBioPortal website was used to evaluate the characteristics of RNMT alteration. The TISDB database was used to obtain the expression of different subtypes. The Tumor Immune Estimation Resource (TIMER) database was used to analyze the association between RNMT and tumor immune infiltration. Gene set enrichment analysis (GSEA) was used to identify the relevant pathways. Results: RNMT was ubiquitously highly expressed across cancers and survival analysis revealed that its expression was highly associated with the clinical prognosis of various cancer types. Remarkably, RNMT participates in immune regulation and plays a crucial part in the tumor microenvironment. A positive association was found between RNMT expression and six immune cell types expression in colon adenocarcinoma, kidney renal clear cell carcinoma, and liver hepatocellular carcinoma. Moreover, RNMT expression was highly associated with immunoregulators in most cancer types, and correlated to TMB, MSI, MMR, and DNMT. Finally, GSEA indicated that RNMT may correlate with tumor immunity.

BackgroundOutdoor traffic-related air pollution has negative effects on respiratory health. In this study, we aimed to explore the effect of outdoor traffic-related air pollution on chronic obstructive pulmonary disease (COPD) in Guangzhou.MethodsWe enrolled 1,460 residents aged 40 years or older between 21 January 2014 and 31 January 2018. We administered questionnaires and spirometry tests. The distance of participants' residences or locations of outdoor activities from busy roads (as indicators of outdoor traffic-related air pollution), indoor air pollution, and smoking history were queried in the questionnaires.ResultsOf the 1,460 residents with valid survey and test results, 292 were diagnosed with COPD, with a detection rate of 20%. Participants who lived and did their outdoor activities near busy roads had a higher detection rate of COPD. Among residents living at distances of <50 meters, 50–199 meters, and more than 200 meters from busy roads, the detection rates were 20.6, 21.2, and 14.8%, respectively; the rates for outdoor activities at these distances were 23.8, 24.5, and 13.7%, respectively (p < 0.05). After adjusting for sex, age, smoking status, family history, and smoking index, the distance of outdoor activities from busy roads was an independent risk factor for COPD. Participants whose outdoor activities were conducted <50 meters and 50–199 meters of main roads had odds ratios of 1.54 (95% confidence interval 1.01–2.36) and 1.84 (95% interval 1.23–2.76) for the risk of COPD in comparison with a distance of more than 200 meters from busy roads.ConclusionsResidents of Guangzhou whose outdoor activities were close to busy roads had a high risk of COPD. Traffic-related air pollution presents a risk to human health and a risk of COPD.

目的 分析汕头地区成人血流感染(loodstream infection,BSI)患者的临床特点、病原菌分布和耐药情况,为本地区临床正确使用抗菌药治疗BSI提供依据.方法 选取汕头市中心医院2017年1月-2019年12月急诊和住院成人血培养阳性并确诊为BSI的患者,回顾性分析BSI患者的临床特点、病原菌分布及耐药性.结果 共有成人BSI患者2040例,其中男1032例,女1008例,年龄18～98岁,平均年龄(62.23±15.91)岁,其中60岁以上占61.13％.绝大多数患者存在1种或以上基础疾病,以2型糖尿病最为常见.总共分离出BSI非重复病原菌2166株,其中,67例患者存在混合感染.病原菌分离数量最多的前3位科室依次为急诊科、血液科和肾内科.分离菌株中,革兰阴性菌1397株,占64.50％,革兰阳性菌726株,占33.52％,真菌43株,占1.98％.居前8位病原菌依次为大肠埃希菌、凝固酶阴性葡萄球菌、肺炎克雷伯菌、金黄色葡萄球菌、草绿色链球菌、鲍曼不动杆菌、肠球菌属和铜绿假单胞菌.有44.09％的大肠埃希菌和15.65％的肺炎克雷伯菌产超广谱β-内酰胺酶(ESBLs);耐甲氧西林的凝固酶阴性葡萄球菌(MRCNS)和金黄色葡萄球菌(MRSA)的检出率分别为72.53％和43.92％.大肠埃希菌和肺炎克雷伯菌对阿米卡星、头孢西丁、β-内酰胺类/β-内酰胺酶抑制剂复方制剂、替加环素和碳青霉烯类具有较高敏感性.鲍曼不动杆菌具有较严重的多重耐药性,而铜绿假单胞菌对多种抗菌药均具有较高的敏感性.未发现耐万古霉素的葡萄球菌和肠球菌属.草绿色链球菌对头孢曲松、喹诺酮类、万古霉素和利奈唑胺具有高度敏感性.结论 本地区成人BSI以老年患者居多,绝大多数患者存在1种或以上基础疾病,病原菌以革兰阴性菌为主,不同病原菌耐药性不同,定期开展BSI病原学监测,可为临床正确使用抗菌药提供帮助.

Almost three billion people in developing countries are exposed to biomass smoke (BS), which predisposes them to developing chronic obstructive pulmonary disease (COPD). COPD is associated with abnormal innate and adaptive immune responses in the lungs and systemic circulation, but the mechanisms underlying BS-COPD development are uncertain. We investigated the role of dendritic cells (DCs) and interleukin (IL)-17A in BS-COPD. We investigated T helper cell responses in the BS-exposed COPD rat model by flow cytometry, quantitative PCR, and enzyme-linked immunosorbent assays. We conducted ex vivo experiments to determine which antigen-presenting cells induce Th17 cell responses. We evaluated the in vitro effects of BS-related particulate matter (BRPM) (2.5 μm) on the function of bone marrow-derived dendritic cells (BMDCs). We found that BS exposure enhanced Th17 responses in the lungs of the COPD-modelled rats, and the stimulated DCs (but not the macrophages) were sufficient to induce naïve CD4 + T cells to produce IL-17A in ex vivo experiments. BRPM significantly enhanced the maturation and activation of DCs through Toll-like receptor 2 (TLR2), but not TLR4, and induced Th17 responses. Therefore, BS activated lung DCs through TLR2, which led to Th17 responses and emphysema in the rats. This process is possibly therapeutically targetable.

目的 探讨慢性阻塞性肺疾病(COPD)并痰结核分枝杆菌阴性肺结核患者多种无创辅助检查对疾病诊断的临床价值.方法 选取诊断为COPD并肺结核患者376例,以痰结核分枝杆菌涂片为分组依据,比较两组间血常规、血沉、C-反应蛋白、降钙素原、T-SPOT.TB、TST等常见无创辅助检查方法,分析对疾病的诊断效能.结果 入选患者337例,其中菌阳组59例、菌阴组278例,菌阴组C-反应蛋白、降钙素原、血沉水平均高于菌阳组(P<0.05);菌阴组TST阳性率高于菌阳组(70.6％vs 15.1％,P<0.05).菌阴组TST敏感度85.61％,T-SPOT.TB敏感度95.68％.结论 C-反应蛋白、降钙素原、血沉水平升高和TST阳性结局与T-SPOT.TB检验结果可为临床诊断COPD并肺结核提供参考依据.

Background The association between diurnal temperature range (DTR) and hospitalization for exacerbation of chronic respiratory diseases (CRD) was rarely reported. Objectives To examine the association between DTR and daily hospital admissions for exacerbation of CRD and find out the potential effect of modifications on this association. Method Data on daily hospitalization for exacerbation of chronic obstructive pulmonary disease (COPD), asthma and bronchiectasis and meteorology measures from 2013 through 2017 were obtained from 21 cities in South China. After controlling the effects of daily mean temperature, relative humidity (RH), particulate matter < 2.5 μm diameter (PM 2.5 ) and other confounding factors, a standard generalized additive model (GAM) with a quasi-Poisson distribution was performed to evaluate the relationships between DTR and daily hospital admissions of CRD in a two-stage strategy. Subgroup analysis was performed to find potential modifications, including seasonality and population characteristics. Result Elevated risk of hospitalization for exacerbation of CRD (RR = 1.09 [95%CI: 1.08 to 1.11]) was associated with the increase in DTR (the 75th percentile versus the 25th percentile of DTR at lag0–6). The effects of DTR on hospital admissions for CRD were strong at low DTR in the hot season and high DTR in the cold season. The RR (the 75th percentile versus the 25th percentile of DTR at lag0–6) of hospitalization was 1.11 (95%CI: 1.08 to 1.12) for exacerbations of COPD and 1.09 (95%CI: 1.05 to 1.13) for asthma. The adverse effect of DTR on hospitalization for bronchiectasis was only observed in female patients (RR = 1.06 [95%CI: 1.03 to 1.10]). Conclusion Our study provided additional evidence for the association between DTR and daily hospitalization for exacerbation of CRD, and these associations are especially stronger in COPD patients and in the cold season than the hot season. Preventive measures to reduce the adverse impacts of DTR were needed for CRD patients.

Aims: To assess possible effect of air quality improvements, we investigated the temporal change in hospital admissions for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) associated with pollutant concentrations. Methods: We collected daily concentrations of particulate matter (i.e., PM2.5, PM10 and PMcoarse), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O-3), and admissions for AECOPD for 21 cities in Guangdong from 2013 to 2017. We examined the association of air pollution with AECOPD admissions using two-stage time-series analysis, and estimated the annual attributable fractions, numbers, and direct hospitalization costs of AECOPD admissions with principal component analysis. Results: From 2013-2017, mean daily concentrations of SO2, PM10 and PM2.5 declined by nearly 40%, 30%, and 26% respectively. As the average daily 8 h O-3 concentration increased considerably, the number of days exceeding WHO target (i.e.,100 mu g/m(3)) increased from 103 in 2015-152 in 2017. For each interquartile range increase in pollutant concentration, the relative risks of AECOPD admission at lag 0-3 were 1.093 (95% CI 1.06-1.13) for PM2.5, 1.092 (95% CI 1.08-1.11) for O-3, and 1.092 (95% CI 1.05-1.14) for SO2. Attributable fractions of AECOPD admission advanced by air pollution declined from 9.5% in 2013 to 4.9% in 2016, then increased to 6.0% in 2017. A similar declining trend was observed for direct AECOPD hospitalization costs. Conclusion: Declined attributable hospital admissions for AECOPD may be associated with the reduction in concentrations of PM2.5, PM10 and SO2 in Guangdong, while O-3 has emerged as an important risk factor. Summarizes the main finding of the work: Reduction in PM may result in declined attributable hospitalizations for AECOPD, while O-3 has emerged as an important risk factor following an intervention.

Background: Tiotropium improves lung function and ameliorates the annual decline in forced expiratory volume in 1 s (FEV1) after bronchodilator use in patients with mild to moderate chronic obstructive pulmonary disease (COPD). However, whether these benefits persist in patients with early-stage COPD after tiotropium discontinuation is unknown. Methods: In this prospective cohort observational follow-up study, patients who had completed the Tiotropium in Early-Stage COPD (Tie-COPD) trial were followed for a maximum of 3 years, continuing or discontinuing treatment according to their willingness. The outcomes measured were spirometry parameters, COPD exacerbations, COPD Assessment Test (CAT) scores, Clinical COPD Questionnaire (CCQ) scores, modified Medical Research Council (mMRC) scores and the use of respiratory medications. Results: Out of 376 patients, 262 (126 in the post-placebo group and 136 in the post-tiotropium group) completed the maximum 3-year follow-up after the study medication was withdrawn. After discontinuation, the decrease in FEV1 and forced vital capacity (FVC) did not differ significantly between the two groups, and neither did their annual decline. In addition, the frequency of acute COPD exacerbations and the mMRC scores were similar between the two groups after medication withdrawal. Both the mean CAT and CCQ scores were significantly lower in the post-tiotropium group than in the post-placebo group (p<0.05 for all comparisons) at the 1-year follow-up after withdrawal, but they were not different at the next follow-up. Conclusion: Withdrawal of tiotropium treatment in early-stage COPD resulted in difference reduction of both FEV1 and FVC, indicating that treatment should be continued.

Background: Tiotropium improves lung function and ameliorates the annual decline in the forced expiratory volume in 1 second (FEV1) after bronchodilator use in patients with mild to moderate chronic obstructive pulmonary disease (COPD). However, whether these benefits persist in patients with early-stage COPD after tiotropium discontinuation is unknown.

Background: Criteria of obstruction that establish a diagnosis of COPD have been debated in recent years. We carried out a follow-up study to assess the impact of the new LLN reference equation for Chinese on detecting COPD compared with the traditional 0.7fixed criteria. Methods: We examined the prevalence and characteristics of airflow limitation for a non-child population using post-bronchodilator airflow with both age-dependent predicted lower limit of the normal value and fixed-ratio spirometric criterion. Questionnaires and spirometry were completed for all eligible subjects during the baseline examination. Participants with inconsistent diagnosis according to the two criteria, normal participants (controls) and COPD patients in stages I or II, were invited to take a cardiopulmonary exercise testing (CPET) examination and follow up for 2-4 years. Results: A total of 5448 (mean age 50.51 +/- 13.2 yr) study subjects with acceptable spirometry and complete questionnaire data were included in our final analyses. COPD detection based on LLN was consistent with the GOLD 0.7 fixed-ratio in general, as 51 subjects (0.9%) were underdiagnosed, and 61 subjects (1.1%) were overdiagnosed when using LLN as the reference diagnostic criterion. The underdiagnosed subjects were younger, had more symptoms, more exposure to biofuels and worse FEV1 than the normal group; they also demonstrated a damaged cardiopulmonary reserve capacity and significant FEV1 decline. Except for being older, the overdiagnosed subjects differed little from the normal group. Conclusions: Individual-dependent LLN appears to better reveal impacts on detecting airflow limitation. Participants underdiagnosed by GOLD criterion should be paid more attention.

Objective To observe the effect of smoking status on lung function in Chinese people >40 years of age by a 2-year longitudinal follow-up.Methods This study prospectively investigated 2 682 cases of pulmonary ventilation function,smoking status,regularity of residents drug combination and gender,age,height,weight and other information,observation time for two years,2 290 people (85.4%) complete the follow-up study.Results Of the 2 290 people,1 197 people (52.3%) are never-smokers,467 people (20.4%) are ex-smokers,626 people (27.3%) are current smokers.There were statistically significant differences in the number of age,sex,BMI,lung function COPD and combination therapy among the three groups.After 2 years of follow-up,results show that the lung function FEV1,FEV1 % pred,FVC,FEV1 / FVC showed decreased year by year.After adjusted the difference variables,It showed that,to compared with never smokers,ex-smokers significantly reduced lung function FEV1,FEV1 %pred and FEV1 / FVC,P values were 0.030,0.011 and <0.001,current smokers significantly reduced lung function FEV1/FVC.Conclusions Never-smokers have the slowest decline in lung function,We advocate non smoking or smoking as early as possible.