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PURPOSE: Sleep disorders are becoming more prevalent in hospitalized patients with acute myocardial infarction (AMI). We aimed to investigate the risk factors for sleep disorders in hospitalized patients with AMI, then develop and validate a prediction nomogram for the risk of sleep disorders. METHODS: Clinical data were collected from patients with AMI hospitalized in our hospital from January 2020 to June 2023. All patients were divided into the training group and the validation group with a ratio of 7:3 in sequential order. The LASSO regression analysis and multivariate logistic regression analysis were used to screen potential risk factors for sleep disorders. The concordance index (C-index), calibration curves, and decision curve analysis (DCA) were plotted. RESULTS: A total of 256 hospitalized patients with AMI were enrolled. Patients were divided into the training group (180) and the validation group (76) according to a scale of 7:3. Of the 256 patients, 90 patients (35.16%) suffered from sleep disorders, and 33 patients (12.89%) needed hypnotics. The variables screened by LASSO regression included age, smoking, NYHA class, anxiety status at admission, depression status at admission, and strangeness of environment. A nomogram model was established by incorporating the risk factors selected. The C-index, calibration curve, and DCA showed good predictive performance. CONCLUSIONS: We identified six clinical characteristics as predictors of sleep disorders in hospitalized patients with AMI. It helps nurses make appropriate decisions in clinical practice.
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Infarto do Miocárdio , Nomogramas , Valor Preditivo dos Testes , Transtornos do Sono-Vigília , Humanos , Masculino , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Medição de Risco , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/epidemiologia , Idoso , Reprodutibilidade dos Testes , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/complicações , Técnicas de Apoio para a Decisão , Prognóstico , Pacientes Internados , Sono , Hospitalização , Estudos Retrospectivos , China/epidemiologiaRESUMO
This study aimed to analyze the effect of Bletilla striata polysaccharide(BSP) on endogenous metabolites in serum of tumor-bearing mice treated with 5-fluorouracil(5-FU) by untargeted metabolomics techniques and explore the mechanism of BSP in alleviating the toxic and side effects induced by 5-FU. Male BALB/C mice were randomly divided into a normal group, a model group, a 5-FU group, and a 5-FU + BSP group, with eight mice in each group. Mouse colon cancer cells(CT26) were transplanted into the mice except for those in the normal group to construct the tumor-bearing mouse model by subcutaneous injection, and 5-FU chemotherapy and BSP treatment were carried out from the second day of modeling. The changes in body weight, diarrhea, and white blood cell count in the peripheral blood were recorded. The mice were sacrificed and sampled when the tumor weight of mice in the model group reached approximately 1 g. TUNEL staining was used to detect the cell apoptosis in the small intestine of each group. The proportions of hematopoietic stem cells and myeloid progenitor cells in bone marrow were measured by flow cytometry. Five serum samples were selected randomly from each group for untargeted metabolomics analysis. The results showed that BSP was not effective in inhibiting colon cancer in mice, but diarrhea, leukopenia, and weight loss caused by 5-FU chemotherapy were significantly improved after BSP intervention. In addition, apoptotic cells decreased in the small intestinal tissues and the percentages of hematopoietic stem cells and myeloid progenitor cells in bone marrow were significantly higher after BSP treatment. Metabolomics results showed that the toxic and side effects of 5-FU resulted in significant decrease in 29 metabolites and significant increase in 22 metabolites in mouse serum. Among them, 19 disordered metabolites showed a return to normal levels in the 5-FU+BSP group. The results of pathway enrichment indicated that metabolic pathways mainly involved pyrimidine metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Therefore, BSP may ameliorate the toxic and side effects of 5-FU in the intestinal tract and bone marrow presumably by regulating nucleotide synthesis, inflammatory damage, and hormone production.
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Neoplasias do Colo , Fluoruracila , Animais , Masculino , Camundongos , Neoplasias do Colo/tratamento farmacológico , Diarreia , Fluoruracila/efeitos adversos , Hormônios , Metabolômica , Camundongos Endogâmicos BALB C , Polissacarídeos/farmacologiaRESUMO
The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and ß-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.
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Neoplasias Associadas a Colite , Colite , Neoplasias do Colo , Camundongos , Animais , Proteína de Ligação a Elemento Regulador de Esterol 1 , PPAR alfa/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Colo , Azoximetano , RNA Mensageiro , Sulfato de Dextrana , Colite/induzido quimicamente , Colite/complicações , Colite/tratamento farmacológico , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
BACKGROUND: Mounting evidence suggests that noncoding RNAs (lncRNAs) were involved in various human cancers. However, the role of these lncRNAs in HPV-driven cervical cancer (CC) has not been extensively studied. Considering that HR-HPV infections contribute to cervical carcinogenesis by regulating the expression of lncRNAs, miRNAs and mRNAs, we aim to systematically analyze lncRNAs and mRNAs expression profile to identify novel lncRNAs-mRNAs co-expression networks and explore their potential impact on tumorigenesis in HPV-driven CC. METHODS: LncRNA/mRNA microarray technology was utilized to identify the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in HPV-16 and HPV-18 cervical carcinogenesis compared to normal cervical tissues. Venn diagram and weighted gene co-expression network analysis (WGCNA) were used to identify the hub DElncRNAs/DEmRNAs that were both significantly correlated with HPV-16 and HPV-18 CC patients. LncRNA-mRNA correlation analysis and functional enrichment pathway analysis were performed on these key DElncRNAs/DEmRNAs in HPV-16 and HPV-18 CC patients to explore their mutual mechanism in HPV-driven CC. A lncRNA-mRNA co-expression score (CES) model was established and validated by using the Cox regression method. Afterward, the clinicopathological characteristics were analyzed between CES-high and CES-low groups. In vitro, functional experiments were performed to evaluate the role of LINC00511 and PGK1 in cell proliferation, migration and invasion in CC cells. To understand whether LINC00511 play as an oncogenic role partially via modulating the expression of PGK1, rescue assays were used. RESULTS: We identified 81 lncRNAs and 211 mRNAs that were commonly differentially expressed in HPV-16 and HPV-18 CC tissues compared to normal tissues. The results of lncRNA-mRNA correlation analysis and functional enrichment pathway analysis showed that the LINC00511-PGK1 co-expression network may make an important contribution to HPV-mediated tumorigenesis and be closely associated with metabolism-related mechanisms. Combined with clinical survival data, the prognostic lncRNA-mRNA co-expression score (CES) model based on LINC00511 and PGK1 could precisely predict patients' overall survival (OS). CES-high patients had a worse prognosis than CES-low patients and the enriched pathways and potential targets of applicable drugs were explored in CES-high patients. In vitro experiments confirmed the oncogenic functions of LINC00511 and PGK1 in the progression of CC, and revealed that LINC00511 functions in an oncogenic role in CC cells partially via modulating the expression of PGK1. CONCLUSIONS: Together, these data identify co-expression modules that provide valuable information to understand the pathogenesis of HPV-mediated tumorigenesis, which highlights the pivotal function of the LINC00511-PGK1 co-expression network in cervical carcinogenesis. Furthermore, our CES model has a reliable predicting ability that could stratify CC patients into low- and high-risk groups of poor survival. This study provides a bioinformatics method to screen prognostic biomarkers which leads to lncRNA-mRNA co-expression network identification and construction for patients' survival prediction and potential drug applications in other cancers.
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MicroRNAs , Infecções por Papillomavirus , RNA Longo não Codificante , Neoplasias do Colo do Útero , Feminino , Humanos , Biomarcadores Tumorais/genética , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/genética , Infecções por Papillomavirus/genética , Fosfoglicerato Quinase/genética , Fosfoglicerato Quinase/metabolismo , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias do Colo do Útero/genéticaRESUMO
To study the effect of anemoside B4 on rats with chronic obstructive pulmonary disease (COPD).Seventy-two SD male rats were randomly divided into blank group and model group.The method of exposure to cigarette smoke and combined with lipopolysaccharide (LPS) was used to replicate the rat model of COPD.After the model was maintained for 5 weeks,the rats were randomly divided into model group,dexamethasone group (0.81 mg·kg~(-1)) and anemoside B4 low,medium and high (2,4,8 mg·kg~(-1)) dose groups,a group of 12 animals were administered,and then the administration was started.The administration was maintained until the28th day,and the pulmonary function parameters of rats were measured by an animal pulmonary function instrument.After testing the rat lung function parameters,immediately draw rat alveolar lavage fluid (BALF),and use high-throughput protein chip technology to determined the expression levels of inflammatory cytokines in rat BALF.HE staining was used to observe the general pathological changes of rat lung and tracheal tissue.Masson staining was used to observe the collagen deposition in rat lung tissue.Real-time q PCR method was used to determine the mRNA expression level of related genes in rat lung tissue.Western blot method was used to determine the expression levels of related proteins in rat lung tissues.According to the findings,compared with the model group,the dexamethasone group and the anemoside B4 drug groups had different degrees of increase in the lung function parameters of rats (P<0.01,P<0.05),improved the expression level of inflammatory cytokines in the BALF of rats to varying degrees (P<0.01,P<0.05),and improved the pathological structure of rat lung tissue to varying degrees.Relative mRNA expressions of matrix metalloproteinase 2 (MMP-2),matrix metalloproteinase 12 (MMP-12),matrix metalloproteinase inhibitor 1 (TIMP-1),interleukin-6 (IL-6),and transforming growth factor-ß1 (TGF-ß1) were significantly reduced (P<0.01);whereas relative mRNA expressions of matrix metalloproteinase 9(MMP-9) and matrix metalloproteinase inhibitor 2 (TIMP-2) were increased significantly (P<0.01).The mRNA and protein expression levels of T-box transcription factor (T-bet),interleukin-12 (IL-12) and signal transducer and activator of transcription 4(STAT4) reduced to varying degrees (P<0.01,P<0.05).The mRNA of transcription factor GATA3 (binding protein-3),interleukin-4 (IL-4) and signal transducer and activator of transcription 6 (STAT6) in rat lung tissues and the protein expression levels of IL-4 and STAT6 were increased to varying degrees (P<0.01,P<0.05).In conclusion,anemoside B4 has a certain protective effect on COPD rats caused by cigarette smoke exposure and combined with LPS.The mechanism of action may be related to the regulation of IL-12/STAT4 and IL-4/STAT6 signaling pathways.
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Doença Pulmonar Obstrutiva Crônica , Fator de Transcrição STAT4 , Animais , Interleucina-12 , Interleucina-4 , Pulmão/metabolismo , Masculino , Metaloproteinase 2 da Matriz , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Ratos , Fator de Transcrição STAT4/metabolismo , Fator de Transcrição STAT6/metabolismo , SaponinasRESUMO
Osteosarcoma is a highly aggressive malignant tumor, which most commonly occurs in children and adolescents. This study aims to reveal that hypoxia promotes the invasion of osteosarcoma cells by up-regulating the expression of NUSAP1. The expression of HIF-1α and NUSAP1 was significantly up-regulated in MG63 cells cultured in hypoxia for 6-36 h. Furthermore, hypoxia induced the migration and invasion of MG63 cells and regulated the level of E-cad, N-cad, Vimentin, Snail, Slug, MMP2, and MMP9 proteins. Importantly, knockdown of NUSAP1 inhibited hypoxia-induced cell migration and invasion. In the hypoxia microenvironment, the addition of HIF-1α inhibitor or the transfection of siRNA specifically targeting HIF-1α significantly reduced the expression of HIF-1α and NUSAP1 and markedly inhibited the migration and invasion of MG63 cells under the hypoxia microenvironment. In conclusion, hypoxia induced the expression of NUSAP1 in a HIF-1α-dependent manner, stimulating the migration and invasion of MG63 cells.
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Patchouli ("Guanghuoxiang") or scientifically known as Pogostemon cablin Benth, belonging to the family Lamiaceae, has been used in traditional Chinse medicine (TCM) since the time of the Eastern Han dynasty. In TCM theory, patchouli can treat colds, nausea, fever, headache, and diarrhea. Various bioactive compounds have been identified in patchouli, including terpenoids, phytosterols, flavonoids, organic acids, lignins, glycosides, alcohols, pyrone, and aldehydes. Among the numerous compounds, patchouli alcohol, ß-patchoulene, patchoulene epoxide, pogostone, and pachypodol are of great importance. The pharmacological impacts of these compounds include anti-peptic ulcer effect, antimicrobial effect, anti-oxidative effect, anti-inflammatory effect, effect on ischemia/reperfusion injury, analgesic effect, antitumor effect, antidiabetic effect, anti-hypertensive effect, immunoregulatory effect, and others.For this review, we examined publications from the previous five years collected from PubMed, Web of Science, Springer, and the Chinese National Knowledge Infrastructure databases. This review summarizes the recent progress in phytochemistry, pharmacology, and mechanisms of action and provides a reference for future studies focused on clinical applications of this important plant extract.
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CONTEXT: The Traditional Chinese herb medicine Dalbergia odorifera T. Chen (Fabaceae), exerted a protective effect on myocardial ischaemia. Latifolin is a neoflavonoid extracted from Dalbergia odorifera. It has been reported to have the effects of anti-inflammation and cardiomyocyte protection. OBJECTIVE: To investigate whether latifolin can improve myocardial infarction (MI) through attenuating myocardial inflammatory and to explore its possible mechanisms. MATERIALS AND METHODS: Left coronary artery was ligated to induce a rat model of MI, and the rats were treated with sodium carboxymethyl cellulose (CMC-Na) or different doses of latifolin (25, 50, 100 mg/kg/d) by oral gavage for 28 days. Serum contents of myocardial enzyme were measured at seven and fourteen days after treatment. Cardiac function, infarct size, histopathological changes and inflammatory cells infiltration was assessed at 28 days after treatment. Western blotting was used to investigate the underlying mechanisms. RESULTS: Latifolin treatment markedly decreased the contents of myocardial enzymes, and increased left ventricular ejection fraction (85.27% vs. 59.11%) and left ventricular fractional shortening (62.71% vs. 45.53%). Latifolin was found to significantly reduced infarction size (27.78% vs. 39.07%), myocardial fibrosis and the numbers of macrophage infiltration (436 cells/mm2 vs. 690 cells/mm2). In addition, latifolin down-regulated the expression levels of hypoxia-inducible factor-1α (0.95-fold), phospho-nuclear factor-κB (0.2-fold) and interleukin-6 (1.11-fold). DISCUSSION AND CONCLUSIONS: Latifolin can protect against myocardial infarction by improving myocardial inflammation through the HIF-1α/NF-κB/IL-6 signalling pathway. Accordingly, latifolin may be a promising drug for pharmacological treatment of ischaemic cardiovascular disease.
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Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Interleucina-6 , Infarto do Miocárdio/prevenção & controle , Miocardite/tratamento farmacológico , NF-kappa B/efeitos dos fármacos , Fenóis/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Dalbergia/química , Enzimas/sangue , Testes de Função Cardíaca , Masculino , Medicina Tradicional Chinesa , Infarto do Miocárdio/patologia , Miocardite/patologia , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Volume SistólicoRESUMO
BACKGROUND: Our previous studies have proved that zinc supplement effectively alleviate depression symptoms in mice, but the mechanisms are still uncertain. Neuroinflammation is considered as an important aspect in pathogenesis of depression. To elucidate the role of zinc on neuroinflammation, in this study, we investigated effects of zinc on lipopolysaccharide (LPS)-induced inflammation in BV2 microglia cells, a kind of innate immune cells in central nervous system. METHODS: BV2 cells were treated by 100â¯ng/ml LPS to induce inflammatory responses and the effects of zinc sulfate (ZnSO4) addition on LPS-induced inflammation were observed. Besides, through culturing HT-22 hippocampus cells by using medium transferred from zinc-intervened BV2 cells, the protective roles of zinc on hippocampus cells were identified. RESULTS: LPS treatment up-regulated expressions of CD11b, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) and level of reactive oxygen species (ROS). Meaningfully, zinc was capable of blocking ROS generation and reducing expressions of the above inflammatory cytokines at both 10⯵M and 30⯵M. In addition, it was proved that zinc intervention to BV2 cells could increase the viabilities of hippocampal HT-22 cells cultured by medium of BV2 cells. Furthermore, the zinc-finger protein A20, an anti-inflammation factor, was increased by zinc supplement, while levels of p65, p-IκB and p-p65 were significantly decreased. LIMITATIONS: More compelling proofs were needed to ensure roles of A20 in anti-inflammatory effects of zinc. CONCLUSIONS: The present results suggested that zinc inhibits inflammatory responses mediated by microglia cells via upregulation of zinc-finger A20. It was proposed that this anti-inflammatory action might be underlying mechanism of previously observed anti-depressive effects of zinc.
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Citocinas/metabolismo , Regulação da Expressão Gênica/fisiologia , Inflamação/tratamento farmacológico , Microglia/efeitos dos fármacos , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Sulfato de Zinco/farmacologia , Animais , Western Blotting , Antígeno CD11b/metabolismo , Linhagem Celular , Sobrevivência Celular , Técnicas de Cocultura , Ciclo-Oxigenase 2/metabolismo , Ensaio de Imunoadsorção Enzimática , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/induzido quimicamente , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , Microglia/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
In this study, we reported a moderately pathogenic pseudorabies virus (PRV) variant isolated from one Bartha-K61-vaccinated pig farm in Weifang, Shandong Province, China, 2014. The sick piglets in the farm were characterized by anorexia, weight loss and neurologic symptoms but did not die. Sequence alignment of the gE gene indicated that it belonged to a new mutated PRV strain and about 15% amino acid sites had mutations, deficiencies and insertions compared to the other PRV strains. The gD gene had two amino acid insertions and ten amino acid mutations in comparison with the Bartha-K61 vaccine strain. The TK and gM genes were the same as one highly pathogenic PRV TJ strain. Evidence from virus isolation, laboratory challenge, serological detection and histopathologic examination confirmed that the etiological agent of the disease is PRV SD1404, which is a moderately pathogenic strain and causes piglets to be sick but not to die. PRV SD1404 strain is different from other reports and should be paid more attention to avoid economic losses.
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Variação Genética , Herpesvirus Suídeo 1/genética , Pseudorraiva/epidemiologia , Pseudorraiva/virologia , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Biópsia , Encéfalo/virologia , Linhagem Celular , Embrião de Galinha , China/epidemiologia , Genoma Viral , Herpesvirus Suídeo 1/classificação , Herpesvirus Suídeo 1/isolamento & purificação , História do Século XXI , Mutação , Filogenia , Pseudorraiva/história , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/história , Doenças dos Suínos/virologia , Proteínas do Envelope Viral/genéticaRESUMO
BACKGROUND: Pulmonary tuberculosis (PTB,both smear positive and smear negative) is an airborne infectious disease of major public health concern in China and other parts of the world where PTB endemicity is reported. This study aims at identifying PTB spatio-temporal clusters and associated risk factors in Zhaotong prefecture-level city, located in southwest China, where the PTB notification rate was higher than the average rate in the entire country. METHODS: Space-time scan statistics were carried out using PTB registered data in the nationwide TB online registration system from 2011 to 2015, to identify spatial clusters. PTB patients diagnosed between October 2015 and February 2016 were selected and a structured questionnaire was administered to collect a set of variables that includes socio-economic status, behavioural characteristics, local environmental and biological characteristics. Based on the discovery of detailed town-level spatio-temporal PTB clusters, we divided selected subjects into two groups including the cases that resides within and outside identified clusters. Then, logistic regression analysis was applied comparing the results of variables between the two groups. RESULTS: A total of 1508 subjects consented and participated in the survey. Clusters for PTB cases were identified in 38 towns distributed over south-western Zhaotong. Logistic regression analysis showed that history of chronic bronchitis (OR = 3.683, 95% CI: 2.180-6.223), living in an urban area (OR = 5.876, 95% CI: 2.381-14.502) and using coal as the main fuel (OR = 9.356, 95% CI: 5.620-15.576) were independently associated with clustering. While, not smoking (OR = 0.340, 95% CI: 0.137-0.843) is the protection factor of spatial clustering. CONCLUSIONS: We found PTB specially clustered in south-western Zhaotong. The strong associated factors influencing the PTB spatial cluster including: the history of chronic bronchitis, living in the urban area, smoking and the use of coal as the main fuel for cooking and heating. Therefore, efforts should be made to curtail these associated factors.
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Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Antituberculosos/uso terapêutico , Bronquite Crônica/fisiopatologia , China/epidemiologia , Cidades , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar/fisiopatologia , Classe Social , Conglomerados Espaço-Temporais , Análise Espaço-Temporal , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/transmissãoRESUMO
GATA2 regulated transcriptional network has been validated requisite for RAS oncogene-driven non-small cell lung cancer (NSCLC). GATA2 has been reported as a SUMOylated protein. In endothelial cells, its transcriptional activity is attenuated by SUMO-2 conjugation, which is specifically catalyzed by its E3 ligase PIASy. In this study, we found a decreased expression of PIASy in RAS mutant NSCLC cell lines and specimens with RAS mutations. Forced expression of PIASy in NSCLC cells inhibits their viability in vitro, as well as tumorigenesis and growth in vivo. Mechanistically, we demonstrated overexpression of PIASy in A549 cells altered the regulated transcriptional network of GATA2, including proteasome, IL-1-signaling, and Rho-signaling pathways. Forced expression of PIASy resulted in the accumulated SUMOylation of GATA2, attenuating its transcriptional activity in A549 cells. These results collectively suggest that PIASy plays an antagonistic role in RAS-driven NSCLC survival, by enhancing the SUMOylation of GATA2 and inhibiting its transcriptional activity.
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Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a key cytoplasm signal adaptor that mediates signals activated by tumor necrosis factor receptor (TNFR) superfamily and the Interleukin-1 receptor/Toll-like receptor (IL-1/TLR) superfamily. The full-length 2492 bp TRAF6 (Sp-TRAF6) from Scylla paramamosain contains 1800 bp of open reading frame (ORF) encoding 598 amino acids, including an N-terminal RING-type zinc finger, two TRAF-type zinc fingers and a conserved C-terminal meprin and TRAF homology (MATH) domain. Multiple alignment analysis shows that the putative amino acid sequence of Sp-TRAf6 has highest identity of 88% with Pt-TRAF6 from Portunus trituberculatus, while the similarity of Sp-TRAF6 with other crustacean sequences was 54-55%. RT-PCR analysis indicated that Sp-TRAF6 transcripts were predominantly expressed in the hepatopancreas and stomach, whereas it was barely detected in the heart and hemocytes in our study. Moreover, Sp-TRAF6 transcripts were significantly up-regulated after Vibrio parahemolyticus and LPS challenges. RNA interference assay was carried out used by siRNA to investigate the genes expression patterns regulated by Sp-TRAF6. The qRT-PCR results showed that silencing Sp-TRAF6 gene could inhibit SpALF1, SpALF2, SpALF5 and SpALF6 expression in hemocytes, while inhibit SpALF1, SpALF3, SpALF4, SpALF5 and SpALF6 expression in hepatopancreas. Taken together, the acute-phase response to immune challenges and the inhibition of SpALFs gene expression indicate that Sp-TRAF6 plays an important role in host defense against pathogen invasions via regulation of ALF gene expression in S. paramamosain.
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Proteínas de Artrópodes/metabolismo , Braquiúros/imunologia , Hepatopâncreas/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Vibrioses/imunologia , Vibrio parahaemolyticus/imunologia , Animais , Proteínas de Artrópodes/genética , Células Cultivadas , Clonagem Molecular , Regulação da Expressão Gênica , Imunidade Inata , Lipopolissacarídeos/imunologia , Filogenia , RNA Interferente Pequeno/genética , Alinhamento de Sequência , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/genética , Receptores Toll-Like/metabolismo , TranscriptomaRESUMO
BACKGROUND: To assess the feasibility and safety of tubeless video-assisted thoracoscopic surgery (VATS) under non-intubated, intravenous anesthesia with spontaneous ventilation and no placement of a chest tube postoperatively compared with VATS under intubated anesthesia with single-lung mechanical ventilation. METHODS: A total of 91 patients undergoing tubeless VATS (60 sympathectomies, 22 bullae resections, and 9 mediastinal tumor resections) between December 2012 and December 2015 were included. Additionally, 82 patients were treated by VATS by the same team while under intubated general anesthesia (52 sympathectomies, 19 bullae resections, and 11 mediastinal tumor resections). Comprehensive early outcome data, including intraoperative and postoperative variables, were compared between the subgroups. RESULTS: In total, 89 patients in the tubeless group underwent an effective operation and exhibited good postoperative recovery, while 2 (one sympathectomy and one bullae resection) had their operation aborted for some reason. The tubeless group showed advantages in the postoperative fasting time, the mean duration of the postoperative hospital stay, and postoperative pain scores, while no significant difference was found in intraoperative blood loss, the operation time or postoperative complications between the tubeless group and the intubated group. Furthermore, 83% (49/59) of sympathectomies, 81% (17/21) of bullae resections, and 56% (5/9) of mediastinal tumor resections were achieved via day surgery. CONCLUSIONS: In this study, our experience has shown that tubeless VATS is a safe and feasible surgery with certain advantages in selected patients with thoracic disease and that we can achieve day surgery in these cases.
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Saliva is secreted by salivary glands and performs a variety of functions, including mouth cleaning and protection, antibacterial activity, and digestion. With the rapid progress in salivaomics, saliva became recognized as a potential pool of biological markers. Being a non-invasive and safe source, saliva is a potential substitute for blood in diagnosis and prognosis of diseases. This review summarizes the latest advancement in saliva-related studies and presents the potential value of saliva in early diagnosis of oral diseases, such as dental caries, periodontal disease, cancer, diabetes, and other systemic disorders. Saliva biomarkers can reveal changes ranging from changes in biochemical index, DNA, RNA, and proteins to the diversification of microbiota structure. By integrating recent data, this paper discusses the clinical significance and application prospect of saliva in early diagnosis of diseases and in translational and precision medicine.
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Saliva , Biomarcadores , Cárie Dentária , Humanos , Microbiota , Doenças da Boca , PrognósticoRESUMO
BACKGROUND: It is estimated that there are about 74,000 primary multidrug-resistant tuberculosis (MDR-TB) patients per year according to the prevalence of MDR-TB of 5.7% among new TB patients in China. Thus, the risks of primary transmission of MDR-TB require further attention. This study aimed to identify the factors associated with primary transmission of MDR-TB in Henan province, where the number of new TB patients is ranked second highest in China. METHODS: A 1:1 matched case-control study was conducted in Henan, China. Cases were primary MDR-TB patients who were individually matched with a healthy control without TB from the same neighborhood. The study was conducted from July 2013 to June 2014. Both case and control were matched by age (±5 years) and sex. Conditional logistic regression was used to compute adjusted odds ratios (AORs) with corresponding 95% confidence intervals (CIs) for risk factors associated with primary MDR-TB. RESULTS: For the study, 146 pairs of participants were recruited. The final multivariable logistic regression model disclosed that after adjusting for age and sex, primary MDR-TB cases were more likely to be single (AOR, 5.4; 95% CI, 1.4-20.7), earn an annual income of ≤ 12,000 yuan (RMB) (AOR, 9.9; 95% CI, 2.0-48.1), experience more life pressure/stress (AOR, 10.8; 95% CI, 2.8-41.5), not be medically insured (AOR, 50.1; 95% CI, 8.2-306.8), and suffer from diabetes, cardiovascular disease or other respiratory diseases, or cancer (AOR, 57.1; 95% CI, 8.6-424.2). CONCLUSIONS: In order to control primary transmission of MDR-TB in China, we recommend that improving the social support, living standards and medical security of the lower social class become a priority.
RESUMO
A human oral microbiota is the ecological community of commensal, symbiotic, and pathogenic microorganisms found in human oral cavity. Oral microbiota exists mostly in the form of a biofilm and maintains a dynamic ecological equilibrium with the host body. However, the disturbance of this ecological balance inevitably causes oral infectious diseases, such as dental caries, apical periodontitis, periodontal diseases, pericoronitis, and craniofacial bone osteomyelitis. Oral microbiota is also correlated with many systemic diseases, including cancer, diabetes mellitus, rheumatoid arthritis, cardiovascular diseases, and preterm birth. Hence, oral microbiota has been considered as a potential biomarker of human diseases. The "Human Microbiome Project" and other metagenomic projects worldwide have advanced our knowledge of the human oral microbiota. The integration of these metadata has been the frontier of oral microbiology to improve clinical translation. By reviewing recent progress on studies involving oral microbiota-related oral and systemic diseases, we aimed to propose the essential role of oral microbiota in the prediction of the onset, progression, and prognosis of oral and systemic diseases. An oral microbiota-based prediction model helps develop a new paradigm of personalized medicine and benefits the human health in the post-metagenomics era.
Assuntos
Biomarcadores , Microbiota , Boca/microbiologia , Doenças Cardiovasculares/microbiologia , Cárie Dentária/microbiologia , Diabetes Mellitus/microbiologia , Humanos , Metagenômica , Doenças da Boca/microbiologia , Neoplasias/microbiologia , Saúde Bucal , Doenças Periodontais/microbiologiaRESUMO
Chromosomal aberration is an important genetic feature of malignant tumor cells. This study aimed to clarify whether BAC DNA could be used to identify chromosome region and arm alterations. For each chromosome region, five to ten 1 Mb BAC DNA clones were selected to construct mixed BAC DNA clones for the particular region. All of the mixed clones from regions which could cover the whole chromosome arm were then mixed to construct mixed BAC DNA clones for the arms. Mixed BAC DNA probes of arms and regions were labeled by degenerate oligonucleotide primed PCR (DOP-PCR) and Nick translation techniques, respectively. The specificities of these probes were validated by fluorescence in situ hybridization (FISH) on the metaphase chromosomes of normal human peripheral blood lymphocytes. FISH with arm-specific mixed BAC DNA probes showed that chromosomal rearrangements and involved chromosome arms were confirmed in several esophageal cancer cells. By using region-specific mixed probes, the breakpoint on 1q from the derivative chromosome t(1q;7q) was identified in 1q32-q41 in esophageal KYSE140 cells. In conclusion, we established an effective labeling method for 1 Mb BAC DNA mixed clone probes, and chromosome arm and region rearrangements could be identified in several esophageal cancer cells by using these probes. Our study provides a more precise method for identification of chromosomal aberration by M-FISH, and the established method may also be applied to the karyotype analysis of hematological malignancies and prenatal diagnosis.
Assuntos
Aberrações Cromossômicas , Cromossomos Artificiais Bacterianos/genética , Cromossomos Humanos/genética , Sondas de DNA/genética , Neoplasias Esofágicas/genética , Humanos , Hibridização in Situ FluorescenteRESUMO
OBJECTIVE: The aim of the study was to analyze the stress distribution in the bone around implants under 0, 5, 10, and 20 degrees of loading. DESIGN: Four mandible models, embedded with cylindrical implants with immediate-load angle of 0, 5, 10, and 20 degrees, were analyzed using the software ANSYS 10.0. The von Mises stress of the implant-bone interface mainly including the implant neck as well as the middle and apex areas was calculated when the implants were loaded with 200-N forces. RESULTS: Stress is mainly concentrated in the bone interface of the implant neck. With the loading implant inclining by 20 degrees, the stress concentrated in the neck of the distal side bone interface is of statistical significance (P < 0.05) when compared with the other groups; when inclined by 0 and 5 degrees, there is no statistical significance; when inclined by 10 degrees, there is statistical significance. The stress in the mesial side of the implant-bone interface is relatively small, and it has no statistical significance in each corresponding site (P > 0.05). CONCLUSIONS: The immediate load of the implant mainly increases the stress in the cortical bone around the neck of the implant. It is necessary to pay attention to the impact of the stress at the angle greater than 20 degrees or above on the implant neck; the stress in change is not obvious in the middle and apex areas of the implant as well as in the middle and apex areas of the implant under a lateral force within 20 degrees.
Assuntos
Implantes Dentários , Análise do Estresse Dentário/métodos , Análise de Elementos Finitos , Carga Imediata em Implante Dentário , Humanos , Imageamento Tridimensional/métodos , Mandíbula , Modelos Biológicos , Estresse MecânicoRESUMO
The poor quality of effluent discharged by municipal wastewater treatment plants (WWTPs) is threatening the safety of water ecology. This study, which integrated a field survey, batch tests, and microbial community identification, was designed to improve the effectiveness of the enhanced biological phosphorus removal (EBPR) process for WWTPs. Over two-thirds of the investigated WWTPs could not achieve total P in effluent lower than 0.5 mg/L, mainly due to the high ratio of chemical oxygen demand to P (28.6-196.2) in the influent. The rates of anaerobic P release and aerobic P uptake for the activated sludge varied from 0.22 to 7.9 mg/g VSS/h and 0.43 to 8.11 mg/g VSS/h, respectively. The fraction of Accumulibacter (PAOs: polyphosphate accumulating organisms) was 4.8 ± 2.0% of the total biomass, while Competibacter (GAOs: glycogen-accumulating organisms) accounted for 4.8 ± 6.4%. The anaerobic P-release rate was found to be an effective indicator of EBPR. Four classifications of the principal components were identified to improve the EBPR effluent quality and sludge activity.