Evaluating the link between DIO3-FA27 promoter methylation, biochemical indices, and heart failure progression.

BACKGROUND: Heart failure (HF) is a disease that poses a serious threat to individual health, and DNA methylation is an important mechanism in epigenetics, and its role in the occurrence and development of the disease has attracted more and more attention. The aim of this study was to evaluate the link between iodothyronine deiodinase 3 promoter region fragment FA27 (DIO3-FA27) methylation levels, biochemical indices, and HF. RESULTS: The methylation levels of DIO3-FA27_CpG_11.12 and DIO3-FA27_CpG_23.24 significantly differed in HF patients with different degrees. Multivariate logistic regression analysis indicated that the relative HF risk in the third and fourth quartiles of activated partial thromboplastin time and fibrin degradation products. The results of the restricted cubic spline model showed that the methylation levels of DIO3-FA 27_CpG_11.12 and DIO3-FA 27_CpG_23.24 were associated with coagulation indicators, liver function, renal function, and blood routine. CONCLUSIONS: Based on the differential analysis of CpG methylation levels based on DIO3-FA27, it was found that biochemical indicators combined with DIO3-FA27 promoter DNA methylation levels could increase the risk of worsening the severity classification of HF patients, which provided a solid foundation and new insights for the study of epigenetic regulation mechanisms in patients with HF.

Perinatal exposure to bisphenol A impairs cognitive function via the gamma-aminobutyric acid signaling pathway in male rat offspring.

Bisphenol A (BPA) is a common synthetic endocrine disruptor that can be utilized in the fabrication of materials such as polycarbonates and epoxy resins. Numerous studies have linked BPA to learning and memory problems, although the precise mechanism remains unknown. Gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the vertebrate central nervous system, and it is intimately related to learning and memory. This study aims to evaluate whether altered cognitive behavior involves the GABA signaling pathway in male offspring of rats exposed to BPA during the prenatal and early postnatal periods. Pregnant rats were orally given BPA (0, 0.04, 0.4, and 4 mg/kg body weight (BW)/day) from the first day of pregnancy to the 21st day of breastfeeding. Three-week-old male rat offspring were selected for an open-field experiment and a new object recognition experiment to evaluate the effect of BPA exposure on cognitive behavior. Furthermore, the role of GABA signaling markers in the cognition affected by BPA was investigated at the molecular level using western blotting and real-time polymerase chain reaction (RT-PCR). The research demonstrated that BPA exposure impacted the behavior and memory of male rat offspring and elevated the expression of glutamic acid decarboxylase 67 (GAD67), GABA type A receptors subunit (GABAARα1), and GABA vesicle transporter (VGAT) in the hippocampus while decreasing the expression levels of GABA transaminase (GABA-T) and GABA transporter 1 (GAT-1). These findings indicate that the alteration in the expression of GABA signaling molecules may be one of the molecular mechanisms by which perinatal exposure to BPA leads to decreased learning and memory in male rat offspring.

Effect of Sleep Quality on Anxiety and Depression Symptoms among College Students in China's Xizang Region: The Mediating Effect of Cognitive Emotion Regulation.

BACKGROUND: While the exact mechanisms are not fully understood, there are significant links between sleep quality, anxiety, depressive symptoms, and cognitive emotion regulation. This research examines how sleep quality affects anxiety and depressive symptoms, as well as the potential of cognitive emotion regulation strategies (CERS) to moderate the impact of sleep quality on these symptoms. METHODS: The Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), the Cognitive Emotion Regulation Questionnaire (CERQ), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder Scale-7 (GAD-7) were all completed online by students from two colleges in China's Xizang region. RESULTS: The study included 4325 subjects. The prevalence of poor sleep quality, anxiety symptoms, and depression symptoms was 45.69%, 36.81%, and 51.86%, respectively. We observed significant direct effects on poor sleep and severity of anxiety/depression: c'1 = 0.586 (0. 544-0.628), and c'2 = 0.728 (0.683-0.773). Adaptive CERS only had a mediating effect on the relationship between sleep quality and depression symptoms, with a1b3 = -0.005 (-0.011--0.001). The link between poor sleep quality and the intensity of anxiety and depression was significantly affected by the indirect effects of maladaptive CERS: effect a2b2 = 0.126 (0.106-0.147), and effect a2b4 = 0.145 (0.123-0.167). CONCLUSIONS: Individuals who experience poor sleep quality are more likely to have increased levels of anxiety and depression. However, enhancing sleep quality led to a decrease in anxiety and depression levels. Adaptive CERS did not predict anxiety, but they did predict depression. Multiple maladaptive CERS could increase levels of anxiety and depression. To prevent mental stress, it is crucial to examine sleep problems among college students, understand their cognitive strategies, promote the adoption of adaptive CERS, and reduce the reliance on maladaptive CERS.

[A Prediction Model for Human Immunodeficiency Virus Infection and Mother-to-Child Transmission Based on the Expression Levels of Selenoprotein Genes].

Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.

Pan-Cancer Study of the Prognosistic Value of Selenium Phosphate Synthase 1.

Objective: This study sought to determine the mean prognostic usefulness of seleniumphosphate synthase (SEPHS1) by investigating its expression in 33 human malignancies and its relationship to tumor immunity.Methods: The expression of selenophosphate synthase 1 (SEPHS1) in 33 human malignant tumors was examined using the Genotype-Tissue Expression (GTEx), Cancer Genome Atlas (TCGA), and TIMER databases. Furthermore, the TCGA cohort was used to investigate relationships between SEPHS1 and immunological checkpoint genes (ICGs), tumor mutation burden (TMB), microsatellite instability (MSI), and DNA mismatch repair genes (MMRs). To establish independent risk factors and calculate survival probabilities for liver hepatocellular carcinoma (LIHC) and brain lower-grade glioma (LGG), Cox regression models and Kaplan-Meier curves were utilized. Eventually, the Genomics of Cancer Drug Sensitivity (GDSC) database was used to evaluate the drug sensitivity in LGG and LIHC patients with high SEPHS1 expression.Results: Overall, in numerous tumor tissues, SEPHS1 was highly expressed, and it significantly linked with the prognosis of LGG, ACC, and LIHC (P < .05). Furthermore, in numerous cancers, SEPHS1 expression was linked to tumor-infiltrating immune cells (TIICs), TMB, MSI, and MMRs. According to univariate and multivariate Cox analyses, SEPHS1 expression was significant for patients with LGG and LIHC.Conclusion: High SEPHS1 expression has a better prognosis for LGG, while low SEPHS1 expression has a better prognosis for LIHC. Chemotherapy was advised for LGG patients, particularly for those with high SEPHS1 expression because it can predict how responsive patients will be to 5-Fluorouracil and Temozolomide. This interaction between SEPHS1 and chemoradiotherapy has a positive clinical impact and may be used as evidence for chemotherapy for LGG and LIHC patients.

Biological Functions of Selenoprotein Glutathione Peroxidases (GPXs) and their Expression in Osteoarthritis.

Purpose: In order to further study the biological functions of glutathione peroxidases (GPXs) and their expression level in patients with osteoarthritis (OA), we fully explored the potential relationship between GPXs and OA. This will provide new ideas for basic biological studies and therapeutic strategies for OA patients. Patients and Methods: In this study, bioinformatics techniques were used to explore the biological functions of five GPXs. The core genes related to the biological functions of GPXs were identified by constructing a protein-protein interaction network (PPI). In addition, we utilized microarray data in public databases to analyze the expression levels of GPXs in OA patients and healthy controls. Finally, we used quantitative real-time polymerase chain reaction (qRT-PCR) to detect the expression of GPXs in OA patients and controls to validate our bioinformatic analysis results. Results: Enrichment analysis showed GPXs were mainly enriched in the glutathione metabolic pathway and participate in the biological process of oxidative stress response, and further play an antioxidant role. The PPI network indicated that superoxide dismutase 1 (SOD1), superoxide dismutase 2(SOD2) and catalase (CAT) were the core proteins of this network. GPX1 was regulated by the greatest number of miRNAs. Experiments showed that the expression of GPX1 was elevated in OA patients compared with controls. Conclusion: GPXs play an important antioxidant role in oxidative stress response. The expression of GPX1 was elevated in peripheral blood mononuclear cells (PBMCs) of OA patients. The changes of GPXs in OA patients may regulate the level of oxidative stress, which may influence synovial lesions and chondrocyte apoptosis.

Expression of m6A Methylation Regulator in Osteoarthritis and Its Prognostic Markers.

OBJECTIVE: Osteoarthritis (OA) is a multifactorial disorder, in which genetic factors are strongly associated with its development. However, the pathogenesis of OA is still unclear, and recently it has been observed that epigenetic modifications are also involved in the pathogenesis of OA. This study aims to study the potential role of m6A-related genes in the occurrence and development of OA. DESIGN: We downloaded the OA expression profile data (GSE55235) from the Gene Expression Omnibus database. First, function enrichment analysis of 17 representative m6A methylation regulatory factors was performed using the DAVID database and Metascape online tool. Then, we analyzed the expression of 17 m6A methylation regulatory factors in OA and the correlation between regulatory factors using Perl software. Finally, receiver operating characteristic (ROC) curve analysis and the area under the ROC curve were used to evaluate the diagnostic effectiveness of m6A-related genes for discriminating patients with OA and healthy. RESULTS: We first identified that 12 of the 17 genes were differentially expressed in OA. ALKBH1, EIF3, IGF2BP3, WTAP, and YTHDC1 were associated with early diagnosis and prognosis of OA. CONCLUSIONS: m6A RNA methylation regulator factors are key players in the progression of OA and have potential role in the stratification of prognosis and the formulation of treatment strategies.

The Role of Selenium-Mediated Notch/Hes1 Signaling Pathway in Kashin-Beck Disease Patients and Cartilage Injury Models.

Kashin-Beck disease (KBD) is a nutrition-related osteoarthropathy, and selenium (Se) deficiency is an environmental risk factor for KBD. Notch/Hes1 signaling pathway plays a vital role in regulating cartilage, but its exact mechanisms in KBD remain unknown. The Se contents were determined using the hydride atomic fluorescence spectrometry assay technique, and the mRNA levels were detected via quantitative real-time PCR. The chondrocyte injury models were established by Se deficiency and tert-butyl hydroperoxide (tBHP), respectively; apoptosis and necrosis rates were detected using Hoechst 33,342/PI and Annexin V-FITC/PI. The results showed that the Se levels in the flour of KBD areas were lower than that of the non-KBD areas, and the Se levels in the plasma of KBD patients were lower than that of the controls. The expressions of Notch1, Jagged1, and Hes1 were higher in the whole blood of KBD patients than those of the controls, and Notch1 was negatively correlated with the expression of BCL2, while was positively correlated with BAX. In injury, chondrocytes induced by low Se and tBHP, the expression of Notch1, Jagged1, and Hes1 increased, apoptosis and necrosis rates increased in Se deficiency and tBHP groups, while Se supplementation reversed it. Decreased plasma Se in KBD patients may be related to low dietary Se. Se deficiency might be involved in the pathological process of KBD by activating the Notch/Hes1 signaling pathway to induce excessive apoptosis of chondrocytes, the activation of Notch/Hes1 promotes oxidative injury, and Se supplementation could reverse it. The importance of Notch/Hes1 signaling pathway in KBD development will provide a new potential target for KBD.

Selenoprotein GPX1 is a prognostic and chemotherapy-related biomarker for brain lower grade glioma.

OBJECTIVE: Glutathione peroxidase 1 (GPX1) is a major selenoprotein in most animal tissues, primarily expressed in the cytoplasm and mitochondria of cells and peroxidase structures of certain cells. GPX1 expression is highly correlated with carcinogenesis and disease progression. The goal of the study was to determine the association between GPX1 expression and tumor therapy, and to identify GPX1 prognostic value in various malignancies. METHODS: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) databases were used to detect the levels of GPX1 expression in human tumor tissues and normal tissues. Indeed, correlations between GPX1 and tumor purity, tumor mutation burden (TMB), microsatellite instability (MSI), and DNA mismatch repair genes (MMRs) were explored using the TCGA cohort. Functional and enrichment analyses were performed by the GeneMANIA database and Gene Set Enrichment Analysis (GSEA), respectively. Cox regression models and Kaplan - Meier curves were used to screen for independent risk factors and estimate brain lower-grade glioma (LGG) survival probability. The Chinese Glioma Genome Atlas (CGGA) database was used to determine whether GPX1 had a race-specific effect on overall survival (OS) in LGG. The cross-interaction between GPX1 and chemoradiotherapy on LGG OS was determined by Kaplan - Meier curves. Logistic regression models of multiplicative interactions were constructed. Furthermore, the relationship between GPX1 and LGG treatment regimens was also explored through the Genomics of Drug Sensitivity in Cancer (GDSC) database. RESULTS: GPX1 was highly expressed in various tumors, GPX1 overexpression was significantly correlated with the poor prognosis of LGG. GPX1 was found to be an independent predictive factor for LGG in both univariate and multivariate Cox models. The nomogram showed a high predictive accuracy (C-index: 0.804, 95% CI: 0.74-0.86). In addition, GPX1 was significantly associated with TMB, MSI, and MMRs in diverse cancers. GPX1 was involved in IL6/JAK/STAT3, inflammatory response, and apoptosis signaling pathways. Besides, non-radiotherapy, chemotherapy, and low GPX1 expression were important factors affecting the better prognosis of LGG. GPX1 acted as a tumor promoter, which has taken the worst effect on LGG survival, but a multiplicative interaction of GPX1*chemoradiotherapy may improve the poor clinical outcome. GPX1 was negatively correlated with the half inhibition concentration (IC50) of temozolomide (TMZ) (Spearman = -0.44, P = 4.52 ×10-26). CONCLUSION: In LGG patients, high GPX1 expression was linked to a shorter OS. The interaction between GPX1 and chemoradiotherapy exhibits a beneficial clinical effect and chemotherapy was recommended for LGG patients, especially for those with high GPX1 expression. Besides, high GPX1 expression can predict TMZ sensitivity in LGG, providing potential evidence for chemotherapy. On the whole, this study presents a wealth of biological as well as clinical significance for the roles of GPX1 in human tumors, particularly in LGG.

Mapping of Global Research on Electronic Cigarettes: A Bibliometric Analysis.

Electronic cigarettes (E-cigarettes) use has increased rapidly in the past decades and has been widely studied by scholars worldwide, whereas the research topics and development trends in this field are still unclear. This study aimed to explore the landscape of research relating to e-cigarettes. The data outputted from the Web of Science Core Collection database was used for bibliometric analysis. Frequencies and percentages were used to describe the publications' characteristics. Visualizing maps were designed using VOSviewer 1.6.9 and CiteSpace 5.8 R2. Overall, a total of 7,979 records were identified in the database and the number of researches increased rapidly since 2010. All publications involved 19837 authors, with the top ten authors contributing to 8.71% (695) of all documents. The most productive country and institution were the United States of America and the University of California San Francisco, respectively. Nicotine & Tobacco Research was not only the journal with the most published papers but also the most co-cited journal. The main research domains in this field were the prevalence, awareness, reasons for using e-cigarettes; e-cigarettes use for tobacco harm reduction; exposure in the population; and the relationship between e-cigarettes and tobacco and nicotine. E-cigarettes researches have become a popular field for scholars. The hot topics on e-cigarette research were extensive and changed over the past decade.

Biological Functions of Selenoprotein Iodothyronine Deiodinase and its Expression in Osteoarthritis.

Objective Iodothyronine deiodinases (DIOs) are important selenoproteins that play a key role in the bone and joint diseases. Osteoarthritis (OA) is the most prevalent joint disease especially in elders. This bioinformatic analysis was performed to explore the role of DIOs in OA pathogenesis. Methods The biological functions of selenoprotein DIOs were analyzed by bioinformatic techniques, including GenCLip 3.0, Database for Annotation, Visualization and Integrated Discovery (DAVID), STRING, Cytoscape, and Network Analyst. The expression of DIOs in the healthy individuals and OA patients was determined by mining OA-related microarray data in the gene expression omnibus (GEO) database of National Center for Biotechnology Information and performing a Meta-analysis of the data with Review Manager 5.3. Results Cluster analysis revealed that the function of the DIOs was associated with thyroid hormone receptor and iodothyronine; GO analysis showed that DIOs were mainly involved in biological processes, such as ethanol metabolism and phenol-containing compound metabolism and primarily involved in the cytochrome P450 metabolism of exogenous organisms and thyroid hormone signaling; SULT1A1 was the core node of the PPI network; miRNAs and thyroid hormones had some iterations with DIO1and DIO2; Meta-analysis showed that DIO3 expression was significantly up-regulated in OA patients (SMD = 0.31, 95%CI: 0.03, 0.59, P = 0.03). Conclusions The main biological functions of DIOs were closely associated with the regulation of thyroid hormone. And the up-regulated expression of DIO3 may have crucial impact on the occurrence of OA.

Glutathione peroxidase family and survival prognosis in patients with renal cell carcinoma. / è°·èƒ±ç”˜è‚½è¿‡æ°§åŒ–ç‰©é ¶å®¶æ—ä¸Žè‚¾ç»†èƒžç™Œæ‚£è€ ç”Ÿå­˜é¢„åŽçš„å ³ç³».

OBJECTIVES: Renal cell carcinoma (RCC) is a renal cortical tumor with high clinical incidence. The effect of glutathione peroxidases (GPXs) on RCC and the possible mechanism are still unclear. This study aims to explore the expression level of GPXs gene in RCC and its effect on the clinical prognosis of patients with RCC via bioinformatics analysis. METHODS: The mRNA expressions of GPXs family genes were obtained from the public data of The Cancer Genome Atlas (TCGA) database. The Kruskal-Wails test was used to analyze the differences in mRNA expression of GPXs family genes between samples from patients with RCC and the normal population. UALAN databases were used to analyze the differences in protein expression of GPXs family genes between samples from patients with renal clear cell carcinoma and the normal population, and to evaluate the role of GPXs family genes in RCC. The Kaplan-Meier Plotter was used to analyze the correlation between different types of RCC and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS). Kaplan-Meier survival curve was drawn based on the GPX8 gene expression to study the relationship between GPX8 gene expression and prognosis of RCC patients. Based on the results of multivariate Cox regression analysis, a Nomogram scoring model for RCC prediction was established by introducing GPX8 gene. RESULTS: The mRNA expressions of GPX1 and GPX4 were higher in the sample of renal chromophobe cell carcinoma, renal clear cell carcinoma, and renal papillary cell carcinoma than those in the normal population (all P<0.01), and GPX7 and GPX8 were significantly over-expressed in patients with renal papillary cell carcinoma and renal clear cell carcinoma (all P<0.01). Compared with the normal group, the protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in renal clear cell carcinoma (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). The protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in patients with renal clear cell carcinoma at different tumor grades (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). Survival analysis showed that OS, DFS, DSS, and PFS were all decreased in patients with clear cell carcinoma compared with patients with papillary cell carcinoma and chromophobe cell carcinoma. According to the GPX8 level, patients were assigned into the low, medium, and high expression groups. Compared with the low GPX8 level group, the OS (P<0.01), DFS (P=0.03), DSS (P<0.01), and PFS (P=3.18×10-7) were significantly decreased in the high level group. Univariate Cox proportional regression analysis showed that the high level of GPX8 was associated with poor OS of 3 different types of renal cancer. Multifactorial analysis showed that GPX8 was an independent factor affecting the OS of patients with renal papillary cell carcinoma. Race and post tumor node metastasis (pTNM) typing were independent factors influencing the OS of patients with renal clear cell carcinoma. GPX8 and pTMN were independent factors influencing the OS of patients with renal chromophobe cell carcinoma. Based on these variables, the Nomogram risk models of 3 types of cell carcinoma were established, and the discrimination and calibration of the models were evaluated using the Consistency index (C-index) and calibration curves. The C-index of the risk model of renal papillary cell carcinoma was 0.62 (95% CI 0.51 to 1.00, P=0.03). The results of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) was 0.88. The C-index of the risk model of renal clear cell carcinoma was 0.72 (95% CI 0.52 to 1.00, P=0.03). The results of ROC curve showed that the AUC was 0.90. The C-index of the risk model of chromophobe cell carcinoma of kidney was 0.90 (95% CI 0.85 to 1.00, P<0.01). The results of ROC curve showed that the AUC was 0.59. CONCLUSIONS: GPXs family genes, especially GPX8, are potential markers for poor prognosis of RCC, and the occurrence and development of RCC can be predicted in clinical practice based on the expressions of GPXs family genes.

Human-to-human transmission of Chlamydia psittaci in China, 2020: an epidemiological and aetiological investigation.

BACKGROUND: Chlamydia psittaci can infect a wide range of avian species, occasionally causing psittacosis (also known as parrot fever) in humans. Most human psittacosis cases are associated with close contact with pet birds or poultry. In December, 2020, an outbreak of severe community-acquired pneumonia of unknown aetiology was reported in a hospital in Shandong province, China, and some of the patients' close contacts had respiratory symptoms. Our aims were to determine the causative agent of this epidemic and whether there had been human-to-human transmission. METHODS: For this epidemiological and aetiological investigation study, we enrolled patients who had community-acquired pneumonia confirmed by chest CT at two local hospitals in Shandong Province in China. We collected sputum, bronchoalveolar lavage fluid, and nasopharyngeal swab samples from participants and detected pathogens by surveying for 22 target respiratory microbes using a commercial assay, followed by metagenomic next-generation sequencing, specific nested PCR, and qPCR tests. We excluded individuals who were C psittaci-negative on both tests. We recruited close contacts of the C psittaci-positive patients, and tested nasopharyngeal swabs from the close contacts and samples from ducks from the processing plant where these patients worked. We then integrated the epidemiological, clinical, and laboratory data to reveal the potential chain of transmission of C psittaci that characterised this outbreak. FINDINGS: Between Dec 4 and 29, 2020, we used metagenomic next-generation sequencing and different PCR-based approaches to test 12 inpatients with community-acquired pneumonia, of whom six (50%) were workers at a duck-meat processing plant and two (17%) were unemployed people, who were positive for C psittaci and enrolled in this study. We contacted 61 close contacts of the six patients who worked at the duck-meat processing plant, of whom 61 (100%) were enrolled and tested, and we determined that the community-acquired pneumonia outbreak was caused by C psittaci. Within the outbreak cluster, 17 (77%) of 22 participants had confirmed C psittaci infections and five (23%) of 22 participants were asymptomatic C psittaci carriers. The outbreak had begun with avian-to-human transmission, and was followed by secondary and tertiary human-to-human transmission, which included transmission by several asymptomatic carriers and by health-care workers. In addition, some of the participants with confirmed C psittaci infection had no identified source of infection, which suggested cryptic bacterial transmission. INTERPRETATION: Our study data might represent the first documented report of human-to-human transmission of C psittaci in China. Therefore, C psittaci has the potential to evolve human-to-human transmission via various routes, should be considered an elevated biosecurity and emergent risk, and be included as part of the routine diagnosis globally, especially for high-risk populations. FUNDING: Academic Promotion Programme of Shandong First Medical University, National Science and Technology Major Project, ARC Australian Laureate Fellowship.

[Expression of Glutathione Peroxidases and Its Effect on Clinical Prognosis in Glioma Patients].

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.

A Bioinformatic Analysis: The Overexpression and Prognostic Potential of GPX7 in Lower-Grade Glioma.

Purpose: Glutathione peroxidase-7 (GPX7) is a newly discovered non-selenium-containing protein with glutathione peroxidase activity, which mainly protects the organism from oxidative damage and is very important for basic biology studies. This study aims to reveal the expression pattern of GPX7 and its prognosis potential from a pan-cancer perspective. Methods: Expression levels of GPX7 in human tumor tissues and normal tissues were evaluated using Human Protein Atlas (HPA), the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and UALCAN databases. The prognostic potential of GPX7 for 33 TCGA tumors was evaluated by Kaplan-Meier analysis and Cox regression analysis. Subsequently, the Chinese Glioma Genome Atlas (CGGA) dataset was used to further verify the expression of GPX7 and its prognostic potential in glioma. We explored the correlation between GPX7 and immune infiltration, tumor mutational burden (TMB) and microsatellite instability (MSI). Furthermore, a nomogram lower-grade glioma (LGG) was constructed to verify the prognostic outcome of patients. Finally, the relationship between GPX7 and treatment regimens for LGG was also explored. Results: GPX7 was overexpressed in multiple tumors. Elevated expression of GPX7 was associated with poor prognosis of LGG patients (OS hazard ratio (HR) = 1.044, P < 0.0001; DFS HR = 1.035, P < 0.0001; PFS HR = 1.045, P < 0.0001). GPX7 was proved to be an independent prognostic factor of LGG through univariate and multivariate Cox analysis. The nomogram confirmed a better predictability (Concordance index (C-index): 0.845; 95% CI, 0.825-0.865). GPX7 was positively correlated with TMB in LGG. GPX7 expression was negatively correlated with half-maximal inhibitory concentration (IC50) of temozolomide (TMZ) (spearman= -0.59, P =1.3e-48). Conclusion: GPX7 was upregulated in multiple tumors, and it was a potential prognostic biomarker in LGG. High-expressed GPX7 can predict the sensitivity of TMZ in LGG patients.

Association Between E-Cigarettes and Asthma in Adolescents: A Systematic Review and Meta-Analysis.

INTRODUCTION: Numerous studies have revealed the relationship between E-cigarettes and asthma but have shown inconsistent results. This study systematically evaluated the potential association between E-cigarette use and asthma in adolescents. METHODS: PubMed, Embase (Ovid), Cochrane Library, and the China Biological Medicine Database were searched for relevant articles published between database inception and February 28, 2021. The quality of included studies was evaluated using the Agency for Healthcare Research and Quality assessment, and a quantitative meta-analysis was conducted to pool outcomes of ORs with 95% CIs. RESULTS: A total of 10 cross-sectional studies incorporating a total of 483,948 participants were included. All the study participants were middle- and high-school students with a mean age of 15-16 years. The median prevalence of ever E-cigarette use was 11.2% (range=2.2%, 45%), and that of current use was 7.5% (range=2.7%, 25%). Overall, E-cigarette use was associated with significantly higher odds of having asthma (pooled OR=1.31, 95% CI=1.22, 1.42) than nonuse, and both current use (OR=1.36, 95% CI=1.26, 1.48) and ever use (OR=1.20, 95% CI=1.12, 1.28) showed similar associations. DISCUSSION: This study shows that both current and ever E-cigarette use have significant associations with asthma in adolescents. This knowledge might provide potential evidence for developing primary prevention strategies and serve as a reference for public health policy.

Crosstalk between CpG Methylation and Polymorphisms (CpG-SNPs) in the Promotor Region of DIO2 in Kashin-Beck Disease.

Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease (KBD). We also analyzed the interaction between the CpGs methylations and CpG-SNPs. Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects. Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The CpGs methylation levels were compared between samples from KBD patients and healthy subjects. The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes. Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls (P <0.05). The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls (P <0.05). The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls. The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype (P <0.05). Conclusion The methylation level of DIO2 increases in KBD patients. Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.

CpG methylation of the GPX3 promoter in patients with Kashin-Beck Disease potentially promotes chondrocyte apoptosis.

OBJECTIVE: To determine the methylation levels of CpGs in the GPX3 promoter region and explore their potential effects on the apoptosis of chondrocytes. METHODS: Blood specimens were collected from 32 participants; 16 KBD patients and 16 healthy subjects. Twenty-five CpGs in the promoter region of GPX3 were identified and detected by MALDI-TOF-MS. Methylation levels of CpGs were compared between KBD patients and healthy subjects as well as among the KBD patients with different degrees. C28/I2 human chondrocytes were treated with tBHP and Na2SeO3. Apoptosis in chondrocytes was examined under a fluorescence microscope. RESULTS: The methylation levels of GPX3-1_CpG_11 and GPX3-1_CpG_16 in KBD patients were significantly higher than those of healthy subjects (P < 0.05). The methylation levels of the other CpGs were not significantly different between the two groups (P > 0.05). The methylation level of GPX3-1_CpG_24 in KBD patients was significantly higher than those of healthy subjects (P < 0.05). MSP-PCR analysis indicated that the methylation rate of KBD group (9.41%) was significantly higher than that of healthy subjects (1.18%), and that GPX3 DNA methylation increased the risk of acquiring KBD 8 fold (OR = 8.000, 95% CI: 1.023-62.580); The mRNA expression of GPX3 in whole blood of KBD patients was lower than that of healthy subjects (P＜0.05); Compared with the control group, GPX3, GPX1 and GPX4 mRNA level of the tertbutyl hydroperoxide injury group decreased significantly (P < 0.05), after supplementation with Na2SeO3. The rate of chondrocytes apoptosis was decreased with the increasing of GPX3 and GPX4 mRNA levels (P＜0.05) and GPX3 mRNA showed a similar trend without statistically significant (P＞0.05). CONCLUSION: The methylation patterns of CpGs in GPX3 varied in KBD patients. The experiments indicated that the increased methylation of CpGs within the GPX3 promoter may down-regulate the expression of GPX3, thereby reducing the antioxidant function of GPX3 and promoting chondrocyte apoptosis, both of which accelerates the occurrence of KBD. We therefore propose a new understanding of GPX3's potential epigenetic and genetic mechanisms that contribute to KBD.

An eQTL variant of ALDH1A2 is associated with Kashin-Beck disease in Chinese population.

INTRODUCTION: The aims of the study were to investigate the relationship between aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and Kashin-Beck disease (KBD), explore the effects of the rs3204689 polymorphism and methylation status on the expression levels of ALDH1A2, and further clarify the pathogenesis of KBD. MATERIALS AND METHODS: The genotype of ALDH1A2 rs3204689 was detected by PCR-RFLP in 103 KBD patients and 109 healthy controls in the whole blood. The mRNA level of ALDH1A2 was measured by qRT-PCR, and the protein expression was detected using IHC staining and Western blotting. The MSP-PCR was used to identify the ALDH1A2 methylation level. RESULTS: There were significant differences in G/G, G/C, and C/C frequencies of ALDH1A2 rs3204689 between the KBD and control groups (χ2 = 7.113, P = 0.029); the minor allele G of ALDH1A2 was associated with the risk of KBD (χ2 = 5.984, P = 0.014). The mRNA and protein levels of ALDH1A2 were increased in the whole blood and cartilage of KBD patients compared with the controls (P = 0.049, P < 0.0001, P = 0.019). Meanwhile, a statistically significant difference was observed between G/G, G/C and C/C genotype on mRNA expression (P = 0.039). The methylation level of the ALDH1A2 gene promoter region showed no significant difference between the KBD and control groups (χ2 = 0.317, P = 0.573). CONCLUSION: Our case-control study indicates that the common variant rs3204689 near ALDH1A2 is associated with KBD in Chinese population. The risk allele G of rs3204689 is statistically linked to the high expression of ALDH1A2, which is up-regulated in the cartilage and whole blood of KBD patients. Our findings suggest a potential role of ALDH1A2 in the pathogenesis of KBD.

Gene and prognostic value of N6-methyladenosine (m6A) modification regulatory factors in lung adenocarcinoma.

Lung cancer is the leading cause of death worldwide, and its incidence continues to increase. The treatment of lung cancer is related to the subtypes and stages of cancer, but the therapeutic effect is still unsatisfactory. We found that 10 of the 13 genes were differentially expressed in lung cancer, YTHDF1, RBM15, HNRNPC, KIAA1429, METTL3 and YTHDF2 are high expression while METTL14, ZC3H13, FTO and WTAP are low expression. HNRNPC and METTL3 genes were associated with the risk and prognosis of LUAD and could regard as biomarkers for early diagnosis and treatment, which provides a theoretical basis for LUAD.