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CH4 serves as an important greenhouse gas, yet limited knowledge is available in global and regional CH4 cycling, particularly in widely distributed karst terrain. In this study, we investigated an upland in Puding Karst Ecosystem Research Station, and explored CH4 concentration and/or flux in atmosphere, soil and cave using a closed static chamber method and an eddy covariance system. Meanwhile, we monitored atmospheric temperature, precipitation, temperature and wind velocity in the cave entrance. The results demonstrated that atmospheric CH4 and actual soil CH4 fluxes in the source area of eddy covariance system were -0.19 ± 8.64 nmols-1m-2 and -0.16 nmols-1m-2 respectively. The CH4 concentrations in Shawan Cave exhibited 10 â¼ 100-fold lower than that of the external atmosphere. CH4 oxidation rate dominated by methane-oxidizing bacteria was 1.98 nmols-1m-2 in Shawan Cave when it combined with temperature difference between cave and external atmosphere. Therefore, CH4 sink in global karst subterranean spaces was estimated at 106.2 Tg CH4 yr-1. We supplemented an understanding of CH4 cycling paths and fluxes in karst terrain, as well as CH4 sinks in karst subterranean space. Further works require to establish a karst ecosystem observation network to conduct long-term integrated studies on CH4 fluxes regarding atmosphere, soils, plants and caves.
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Atmosfera , Cavernas , Metano , Solo , Metano/análise , Metano/metabolismo , Atmosfera/química , Solo/química , Monitoramento Ambiental/métodos , Microbiologia do Solo , Poluentes Atmosféricos/análiseRESUMO
Background: In recent years, Tiaoshen acupuncture in Traditional Chinese Medicine (TCM) has been employed for treating patients with insomnia, but the clinical efficacy remains to be substantiated. Objective: To assess the efficacy and safety of acupuncture in treating insomnia using the Tiaoshen method in TCM. Design: A systematic review and meta-analysis was conducted. Setting: The research was conducted in Shenzhen. Methods: Electronic databases, including Chinese National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, Weipu, PubMed, Web of Science, EMBASE, and Cochrane databases, were retrieved up to September 15, 2023. Randomized controlled trials (RCTs) meeting inclusion criteria were screened. Quality assessment of included articles was performed using the Cochrane Risk of Bias tool. Valid data were then extracted and analyzed via meta-analysis using Review Manager 5.3. The study was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 2023100051. Results: A total of 13 articles were included, comprising 849 patients with insomnia (diagnosed as chronic insomnia or primary insomnia). Meta-analysis results indicated that acupuncture with the Tiaoshen method could decrease the Pittsburgh Sleep Quality Index (PSQI) score [RR=-3.03, 95% CI (-3.73, -2.33), P < .00001], hyperarousal (HAS) scale score [RR=-7.75, 95% CI (-12.29, -3.22), P < .0008], and fatigue scale-14 (FS-14) score [RR=-2.11, 95% CI (-2.83, -1.38), P < .00001] compared with superficial acupuncture on non-effective acupoints or conventional acupuncture manipulation. Additionally, acupuncture with the Tiaoshen method demonstrated safety. However, the funnel plot suggested the presence of publication bias. Conclusions: Acupuncture with the Tiaoshen method could enhance sleep quality and efficiency. Due to the low quality of some literature, further high-quality RCTs are needed to improve the level of evidence.
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Exciton localization through nanoscale strain has been used to create highly efficient single-photon emitters (SPEs) in 2D materials. However, the strong Coulomb interactions between excitons can lead to nonradiative recombination through exciton-exciton annihilation, negatively impacting SPE performance. Here, we investigate the effect of Coulomb interactions on the brightness, single photon purity, and operating temperatures of strain-localized GaSe SPEs by using electrostatic doping. By gating GaSe to the charge neutrality point, the exciton-exciton annihilation nonradiative pathway is suppressed, leading to â¼60% improvement of emission intensity and an enhancement of the single photon purity g(2)(0) from 0.55 to 0.28. The operating temperature also increased from 4.5 K to 85 K consequently. This research provides insight into many-body interactions in excitons confined by nanoscale strain and lays the groundwork for the optimization of SPEs for optoelectronics and quantum photonics.
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SUMMARY: Pathway analysis is widely used in genomics and omics research, but the data visualization has been highly limited in function, pathway coverage and data format. Here, we develop SBGNview a comprehensive R package to address these needs. By adopting the standard SBGN format, SBGNview greatly extend the coverage of pathway-based analysis and data visualization to essentially all major pathway databases beyond KEGG, including 5200 reference pathways and over 3000 species. In addition, SBGNview substantially extends or exceeds current tools (esp. Pathview) in both design and function, including standard input format (SBGN), high-quality output graphics (SVG format) convenient for both interpretation and further update, and flexible and open-end workflow for iterative editing and interactive visualization (Highlighter module). In addition to pathway analysis and data visualization, SBGNview provides essential infrastructure for SBGN data manipulation and processing. AVAILABILITY AND IMPLEMENTATION: The data underlying this article are available as part of the SBGNview package is available on both GitHub and Bioconductor: https://github.com/datapplab/SBGNview, https://bioconductor.org/packages/SBGNview. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Genômica , Software , Visualização de Dados , Bases de Dados Factuais , Análise de DadosRESUMO
Leachate from wet phosphogypsum (PG) stack should be properly managed to mitigate the negative environmental impact of phosphoric industry. Accurate prediction of leachate amount is the prerequisite for efficient leachate management. In this study, a model using water balance analysis to predict leachate production from wet PG stack is established. The extruded water, which is related to PG deformation, is innovatively introduced as a variable in the model to account for the porewater's contribution. Model simulation suggested that at the early stage, fresh water need to be added to PG to facilitate the transfer or PG slurries; however, as the leachate accumulates in the tailings pond, a net discharge of PG is required starting at the fourth year for the studied PG stack. Model simulation also indicated that the leachate generation increased gradually over time and that the leachate generation in each month could deviate from the average leachate generation during the life cycle of the stack. The model output matches with measured values reasonably well, which confirmed the model's accuracy. Sensitivity analysis indicated that average precipitation and evaporation are the two most important factors that determine leachate generation rate. Monthly leachate generation rates vary significantly within the year, as the precipitation and evaporation vary in different seasons. The highest leachate generation rates were reached in rainy seasons and the lowest rates were reached in wintery months. This study could be used to optimize the PG leachate managements and to mitigate the PG related pollution to the environment.
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Eliminação de Resíduos , Poluentes Químicos da Água , Sulfato de Cálcio , Modelos Teóricos , Fósforo , Água , Poluentes Químicos da Água/análiseRESUMO
Importance: Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). Objective: To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. Design, Setting, and Participants: This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022. Interventions: Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]). Main Outcomes and Measures: The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms). Results: Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation. Conclusions and Relevance: Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02633202.
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Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Cisplatino , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Infecções por Vírus Epstein-Barr/complicações , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/etiologia , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/etiologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Qualidade de Vida , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodosRESUMO
OBJECTIVES: To design a standardized imaging diagnostic reporting mode for screening coronavirus disease 2019 (COVID-19), and to prospectively verify its effectiveness in clinical practice. METHODS: A new classification and standardized imaging diagnosis report mode of viral pneumonia was established by studying and summarizing the imaging findings of various kinds of viral pneumonia, combining with lesion density, interstitial changes, pleural effusion, lymph nodes, and some special signs. After systematic training, the radiologist experienced clinical practice for screening CT features. COVID-19 cases were screened retrospectively in the single-center. The confirmed cases were verified, and the diagnostic efficacy of the standardized imaging reporting system in screening COVID-19 was tested. RESULTS: There were 912 patients in this stage receiving the screening imaging examination. Of them, 190 patients were screened in the report mode and 30 patients were diagnosed as COVID-19. The CT manifestation of COVID-19 was characterized by pure ground glass lesions or with a few solid components, predominant subpleural distribution, no lymph node enlargement and pleural effusion, and often with paving-way sign and air bronchus sign. In combination with the above signs, the diagnostic efficacy of COVID-19 was 0.942. CONCLUSIONS: The standardized imaging diagnosis report mode based on COVID-19 chest image features is effective and practical, which should be popularized.
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Betacoronavirus , COVID-19 , Infecções por Coronavirus/diagnóstico , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios XRESUMO
Although continuous outbreak of coronavirus disease 2019, it has been widely reported, there were few reports regarding family cases. We reported a group of family cluster outbreak cases confirmed in Xiangya Hospital, Central South University, China, and their clinical and image characteristics have been analyzed in order to provide reference for the prevention and early diagnosis of this disease. A total of 5 patients from one family, including 4 adults and 1 child, had a history of human contact in Wuhan, Hubei. Four adult patients showed different symptoms, including cough, fever, pharyngeal pain, and dyspnea, while the child patient had no symptoms. Laboratory examination showed no abnormality in all the patients except for slight increase in CRP in 2 patients and mild abnormal liver function index in 1 patient. The chest CT showed that all patients had abnormal images, with different degrees of manifestations.All patients were finally diagnosed by the nucleic acid test.
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Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Adulto , COVID-19 , Criança , China , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Humanos , Pneumonia Viral/epidemiologia , SARS-CoV-2RESUMO
OBJECTIVES: To investigate the role of chest CT for the diagnostic work-up for patients with suspected infection of coronavirus disease 2019 (COVID-19). METHODS: The clinical data and imaging findings of the first nucleic acid-negative COVID-19 patients were analyzed and compared with the first nucleic acid-positive patients. RESULTS: Compared with the first nucleic acid-positive patients, the onset time of the first nucleic acid-negative patients was shorter [(3.58±2.94) d], but the diagnosis was longer [(3.92±3.66) d]. There were no significant differences in the characteristics of the clinical data and radiological findings between the 2 groups (P>0.05). CONCLUSION: Chest CT examination is important to avoid COVID-19 missed diagnosis due to false negative nucleic acid.
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Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , COVID-19 , Humanos , Pandemias , SARS-CoV-2 , Tomografia Computadorizada por Raios XRESUMO
Telomere-associated position-effect variegation (TPEV) in budding yeast has been used as a model for understanding epigenetic inheritance and gene silencing. A widely used assay to identify mutants with improper TPEV employs the URA3 gene at the telomere of chromosome VII-L that can be counterselected with 5-fluoroorotic acid (5-FOA). 5-FOA resistance has been inferred to represent lack of transcription of URA3 and therefore to represent heterochromatin-induced gene silencing. For two genes implicated in telomere silencing, POL30 and DOT1, we show that the URA3 telomere reporter assay does not reflect their role in heterochromatin formation. Rather, an imbalance in ribonucleotide reductase (RNR), which is induced by 5-FOA, and the specific promoter of URA3 fused to ADH4 at telomere VII-L are jointly responsible for the variegated phenotype. We conclude that metabolic changes caused by the drug employed and certain mutants being studied are incompatible with the use of certain prototrophic markers for TPEV.
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Inativação Gênica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Telômero/genética , Telômero/metabolismo , Antígenos Nucleares/genética , Antígenos Nucleares/metabolismo , Efeitos da Posição Cromossômica , Genes Fúngicos , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Modelos Genéticos , Mutação , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Ácido Orótico/análogos & derivados , Ácido Orótico/metabolismo , Antígeno Nuclear de Célula em Proliferação , Ribonucleotídeo Redutases/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
Pathway analysis is widely used in omics studies. Pathway-based data integration and visualization is a critical component of the analysis. To address this need, we recently developed a novel R package called Pathview. Pathview maps, integrates and renders a large variety of biological data onto molecular pathway graphs. Here we developed the Pathview Web server, as to make pathway visualization and data integration accessible to all scientists, including those without the special computing skills or resources. Pathview Web features an intuitive graphical web interface and a user centered design. The server not only expands the core functions of Pathview, but also provides many useful features not available in the offline R package. Importantly, the server presents a comprehensive workflow for both regular and integrated pathway analysis of multiple omics data. In addition, the server also provides a RESTful API for programmatic access and conveniently integration in third-party software or workflows. Pathview Web is openly and freely accessible at https://pathview.uncc.edu/.
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Software , Gráficos por Computador , Expressão Gênica , Internet , Metabolômica , Interface Usuário-ComputadorRESUMO
Cellular senescence acts as a potent barrier to tumorigenesis and contributes to the anti-tumor activity of certain chemotherapeutic agents. Senescent cells undergo a stable cell cycle arrest controlled by RB and p53 and, in addition, display a senescence-associated secretory phenotype (SASP) involving the production of factors that reinforce the senescence arrest, alter the microenvironment, and trigger immune surveillance of the senescent cells. Through a proteomics analysis of senescent chromatin, we identified the nuclear factor-κB (NF-κB) subunit p65 as a major transcription factor that accumulates on chromatin of senescent cells. We found that NF-κB acts as a master regulator of the SASP, influencing the expression of more genes than RB and p53 combined. In cultured fibroblasts, NF-κB suppression causes escape from immune recognition by natural killer (NK) cells and cooperates with p53 inactivation to bypass senescence. In a mouse lymphoma model, NF-κB inhibition bypasses treatment-induced senescence, producing drug resistance, early relapse, and reduced survival. Our results demonstrate that NF-κB controls both cell-autonomous and non-cell-autonomous aspects of the senescence program and identify a tumor-suppressive function of NF-κB that contributes to the outcome of cancer therapy.
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Senescência Celular/fisiologia , Resistência a Medicamentos/fisiologia , Fenótipo , Fator de Transcrição RelA/metabolismo , Animais , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Linfoma/metabolismo , Camundongos , Inibidores da Síntese de Proteínas/farmacologia , RNA Interferente Pequeno/metabolismo , Tetraciclina/farmacologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
Although human cancers have complex genotypes and are genomically unstable, they often remain dependent on the continued presence of single-driver mutations-a phenomenon dubbed "oncogene addiction." Such dependencies have been demonstrated in mouse models, where conditional expression systems have revealed that oncogenes able to initiate cancer are often required for tumor maintenance and progression, thus validating the pathways they control as therapeutic targets. Here, we implement an integrative approach that combines genetically defined mouse models, transcriptional profiling, and a novel inducible RNAi platform to characterize cellular programs that underlie addiction to MLL-AF9-a fusion oncoprotein involved in aggressive forms of acute myeloid leukemia (AML). We show that MLL-AF9 contributes to leukemia maintenance by enforcing a Myb-coordinated program of aberrant self-renewal involving genes linked to leukemia stem cell potential and poor prognosis in human AML. Accordingly, partial and transient Myb suppression precisely phenocopies MLL-AF9 withdrawal and eradicates aggressive AML in vivo without preventing normal myelopoiesis, indicating that strategies to inhibit Myb-dependent aberrant self-renewal programs hold promise as effective and cancer-specific therapeutics. Together, our results identify Myb as a critical mediator of oncogene addiction in AML, delineate relevant Myb target genes that are amenable to pharmacologic inhibition, and establish a general approach for dissecting oncogene addiction in vivo.
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Regulação Neoplásica da Expressão Gênica , Leucemia/fisiopatologia , Oncogenes/fisiologia , Proteínas Proto-Oncogênicas c-myb/metabolismo , Animais , Modelos Animais de Doenças , Genes myb/genética , Hematopoese , Camundongos , Proteínas de Fusão Oncogênica/metabolismo , Oncogenes/genética , Proteínas Proto-Oncogênicas c-myb/genética , Interferência de RNARESUMO
The uncertainties of China's gross primary productivity (GPP) estimates by global data-oriented products and ecosystem models justify a development of high-resolution data-oriented GPP dataset over China. We applied a machine learning algorithm developing a new GPP dataset for China with 0.1° spatial resolution and monthly temporal frequency based on eddy flux measurements from 40 sites in China and surrounding countries, most of which have not been explored in previous global GPP datasets. According to our estimates, mean annual GPP over China is 6.62 ± 0.23 PgC/year during 1982-2015 with a clear gradient from southeast to northwest. The trend of GPP estimated by this study (0.020 ± 0.002 PgC/year2 from 1982 to 2015) is almost two times of that estimated by the previous global dataset. The GPP increment is widely spread with 60% area showing significant increasing trend (p < .05), except for Inner Mongolia. Most ecosystem models overestimated the GPP magnitudes but underestimated the temporal trend of GPP. The monsoon affected eastern China, in particular the area surrounding Qinling Mountain, seems having larger contribution to interannual variability (IAV) of China's GPP than the semiarid northwestern China and Tibetan Plateau. At country scale, temperature is the dominant climatic driver for IAV of GPP. The area where IAV of GPP dominated by temperature is about 42%, while precipitation and solar radiation dominate 31% and 27% respectively over semiarid area and cold-wet area. Such spatial pattern was generally consistent with global GPP dataset, except over the Tibetan Plateau and northeastern forests, but not captured by most ecosystem models, highlighting future research needs to improve the modeling of ecosystem response to climate variations.
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Agricultura/tendências , Mudança Climática , Ecossistema , China , Temperatura , IncertezaRESUMO
OBJECTIVE: To study the potential effects of intensity modulated radiation therapy (IMRT) on clinical efficacy, oral mucosa reaction and immunological foundation; and to explore the effect of immunological changes on clinical efficacy and oral mucosa reaction in patients with nasopharyngeal carcinoma.â© Methods: A total of 200 patients with nasopharyngeal carcinoma, who came from First Department of Nasopharyngeal Radiotherapy, the First People's Hospital of Foshan from October 2008 to November 2011, were selected. The patients were treated with nasopharyngeal radiotherapy, and divided into an observation group and a control group (n=100 in each group). The control group underwent common conventional two-dimensional radiotherapy treatment, while the observation group underwent IMRT. The 5-year survival rates and recurrence rates were recorded at follow-up. After the radiotherapy, the oral mucosa in the patients were evaluated by the classification standard of acute radioactive mucositis by American Radiotherapy Oncology Group (RTOG), and the number of T lymphocyte subsets before and after treatment was detected.â© Results: There were significant difference in non-regional-recurrence survival rate, disease-free survival rate, local recurrence rate between the above 2 groups (all P<0.05), but no significant difference in the distant metastasis-free survival rate (P>0.05). The acute oral mucosa reactions of grade 1, 2, 3, 4 in the control group were 8.00%, 20.00%, 12.00%, 7.00%, respectively, and those were 7.00%, 22.00%, 15.00%, 1.00% respectively. There was no significant difference in the acute response of oral mucosa in grade 1, 2 and 3 in the 2 groups (all P>0.05), but there was significant difference in the grade 4 (P<0.05). There were significantly difference in CD8+, CD4+/ CD8+ and CD4+ T lymphocyte subsets before and after treatment in the above 2 groups (all P<0.01); there were also significantly difference after treatment between the observation group and the control group (all P<0.01).â© Conclusion: In the process of treatment in patients with nasopharyngeal carcinoma, the use of IMRT on the basis of chemotherapy is more effective than the conventional two-dimensional radiotherapy, which can reduce the proportion of grade 4 (severe) acute oral mucosa reaction. It may be related to the protective effect of IMRT on immune function in the patients.
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Carcinoma/radioterapia , Imunidade/efeitos da radiação , Mucosa Bucal/efeitos da radiação , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada , Carcinoma/imunologia , Carcinoma/mortalidade , Intervalo Livre de Doença , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/mortalidade , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do TratamentoRESUMO
We report uniform layer-by-layer sublimation of black phosphorus under heating below 600 K. The uniformity and crystallinity of BP samples after thermal thinning were confirmed by Raman spectra and Raman mapping. The sublimation rate of BP was around 0.18 nm min-1 at 500 K and 1.15 nm min-1 at 550 K. Both room and high temperature Raman peak intensity ratio [Formula: see text] as functions of BP thickness were established for in situ thickness determination and control. Uniform and crystalline 2 to 4-layer BP flakes with areas from 10 to 1000 µm2 were prepared with this method. No micron scale defects were observed. The sublimation thinning method was shown to be a controllable and scalable approach to prepare high-quality few-layer black phosphorus.
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The genetic heterogeneity of cancer influences the trajectory of tumor progression and may underlie clinical variation in therapy response. To model such heterogeneity, we produced genetically and pathologically accurate mouse models of common forms of human acute myeloid leukemia (AML) and developed methods to mimic standard induction chemotherapy and efficiently monitor therapy response. We see that murine AMLs harboring two common human AML genotypes show remarkably diverse responses to conventional therapy that mirror clinical experience. Specifically, murine leukemias expressing the AML1/ETO fusion oncoprotein, associated with a favorable prognosis in patients, show a dramatic response to induction chemotherapy owing to robust activation of the p53 tumor suppressor network. Conversely, murine leukemias expressing MLL fusion proteins, associated with a dismal prognosis in patients, are drug-resistant due to an attenuated p53 response. Our studies highlight the importance of genetic information in guiding the treatment of human AML, functionally establish the p53 network as a central determinant of chemotherapy response in AML, and demonstrate that genetically engineered mouse models of human cancer can accurately predict therapy response in patients.
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Antineoplásicos/uso terapêutico , Modelos Animais de Doenças , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Camundongos Endogâmicos C57BL , Animais , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes ras/genética , Genes ras/fisiologia , Genótipo , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/fisiopatologia , Camundongos , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética , Prognóstico , Proteína 1 Parceira de Translocação de RUNX1 , Proteína Supressora de Tumor p53/genéticaRESUMO
The large chromosomal deletions frequently observed in cancer genomes are often thought to arise as a "two-hit" mechanism in the process of tumor-suppressor gene (TSG) inactivation. Using a murine model system of hepatocellular carcinoma (HCC) and in vivo RNAi, we test an alternative hypothesis, that such deletions can arise from selective pressure to attenuate the activity of multiple genes. By targeting the mouse orthologs of genes frequently deleted on human 8p22 and adjacent regions, which are lost in approximately half of several other major epithelial cancers, we provide evidence suggesting that multiple genes on chromosome 8p can cooperatively inhibit tumorigenesis in mice, and that their cosuppression can synergistically promote tumor growth. In addition, in human HCC patients, the combined down-regulation of functionally validated 8p TSGs is associated with poor survival, in contrast to the down-regulation of any individual gene. Our data imply that large cancer-associated deletions can produce phenotypes distinct from those arising through loss of a single TSG, and as such should be considered and studied as distinct mutational events.
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Carcinoma Hepatocelular/genética , Deleção de Genes , Genes Supressores de Tumor/fisiologia , Genômica/métodos , Neoplasias Hepáticas Experimentais/genética , Monossomia , Animais , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Transformada , Linhagem Celular Tumoral , Cromossomos Humanos Par 8 , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Haploinsuficiência/genética , Humanos , Fígado/citologia , Neoplasias Hepáticas Experimentais/mortalidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Interferência de RNA , Células-Tronco/citologiaRESUMO
SUMMARY: Pathview is a novel tool set for pathway-based data integration and visualization. It maps and renders user data on relevant pathway graphs. Users only need to supply their data and specify the target pathway. Pathview automatically downloads the pathway graph data, parses the data file, maps and integrates user data onto the pathway and renders pathway graphs with the mapped data. Although built as a stand-alone program, Pathview may seamlessly integrate with pathway and functional analysis tools for large-scale and fully automated analysis pipelines. AVAILABILITY: The package is freely available under the GPLv3 license through Bioconductor and R-Forge. It is available at http://bioconductor.org/packages/release/bioc/html/pathview.html and at http://Pathview.r-forge.r-project.org/. CONTACT: luo_weijun@yahoo.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Gráficos por Computador , Software , Expressão Gênica , Redes e Vias Metabólicas , Transdução de Sinais , Integração de SistemasRESUMO
BACKGROUND: Coronary heart disease and type 2 diabetes mellitus (T2DM) frequently coexist, creating a complex and challenging clinical scenario, particularly when complicated with acute myocardial infarction (AMI). AIM: To examine the effects of dapagliflozin combined with sakubactrovalsartan sodium tablets on myocardial microperfusion. METHODS: In total, 98 patients were categorized into control (n = 47) and observation (n = 51) groups. The control group received noxital, while the observation group was treated with dapagliflozin combined with noxital for 6 months. Changes in myocardial microperfusion, blood glucose level, cardiac function, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, growth differentiation factor-15 (GDF-15) level, and other related factors were compared between the two groups. Additionally, the incidence of major adverse cardiovascular events (MACE) and adverse reactions were calculated. RESULTS: After treatment, in the observation and control groups, the corrected thrombolysis in myocardial infarction frame counts were 37.12 ± 5.02 and 48.23 ± 4.66, respectively. The NT-proBNP levels were 1502.65 ± 255.87 and 2015.23 ± 286.31 pg/mL, the N-terminal pro-atrial natriuretic peptide (NT-proANP) levels were 1415.69 ± 213.05 and 1875.52 ± 241.02 ng/mL, the GDF-15 levels were 0.87 ± 0.43 and 1.21 ± 0.56 g/L, and the high-sensitivity C-reactive protein (hs-CRP) levels were 6.54 ± 1.56 and 8.77 ± 1.94 mg/L, respectively, with statistically significant differences (P < 0.05). The cumulative incidence of MACEs in the observation group was significantly lower than that in the control group (P < 0.05). The incidence of adverse reactions was 13.73% (7/51) in the observation group and 10.64% (5/47) in the control group, with no statistically significant difference (P > 0.05). CONCLUSION: Dapagliflozin combined with nocinto can improve myocardial microperfusion and left ventricular remodeling and reduce MACE incidence in patients with post-AMI heart failure and T2DM. The underlying mechanism may be related to the reduction in the expression levels of NT-proANP, GDF-15, and hs-CRP.