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1.
Huan Jing Ke Xue ; 42(10): 4660-4668, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34581108

RESUMO

Under certain terrain and weather conditions, mountain-valley circulation is one of the main meteorological factors affecting aerosol pollution in plain-mountain area. Based on environmental monitoring data and multi-source meteorological data for the Beijing-Tianjin-Hebei region between 2015 and 2019, the characteristics, similarities, and differences of mountain-valley winds in the Beijing Plain and Yanhuai Basin regions were compared. The results show that the mountain-valley winds recorded at the Beijing Observatory are from southwest to northeast compared to from the southeast to northeast at Yanqing station. With the aggravation of pollution levels, the mountain-valley wind intensity decreased by 17.7%-32.4%. When the wind speed at Beijing Observatory was 2-6 m·s-1, the maximum PM2.5 concentration in southeast was 83 µg·m-3, which was higher than in the southwest. When the wind speed at the Yanqing station was 2-6 m·s-1, the PM2.5 concentrations in SE-SSE area was 20-40 µg·m-3 higher than in other directions, and the concentrations in the valley winds were 10-12 µg·m-3 higher than the average value for the last five years. Taking the typical heavy pollution event on March 5-8, 2015, as an example, the influence of mountain-valley winds is mainly reflected in the high humidity and regional transmission of southeast winds during the valley wind stage. The PM2.5 concentrations at the Yanqing station increased by 100-130 µg·m-3 during the valley wind stage on March 6 and 7, 2015. The inversion temperature developed to 1000 m during the mountain wind stage, the local dew point at the Beijing Observatory and the Yanqing station rose by approximately 18℃. The peak dew point at the Yanqing station occurring 2 hours after the Beijing Observatory, and the concentrations of PM2.5 rose slightly under high humidity conditions. Meanwhile, the thermal gradient between the 400-m-high Yanqing Station and Yudu Mountain gradually decreased, and the mountain-valley wind decreased by 8% and 6%, respectively. The weakening of local circulation may be related to the bidirectional feedback mechanism of the boundary layer and high concentrations of aerosols.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Pequim , China , Monitoramento Ambiental , Material Particulado/análise , Estações do Ano , Tempo (Meteorologia) , Vento
2.
Artigo em Inglês | MEDLINE | ID: mdl-34236968

RESUMO

Glutarylation is a type of post-translational modification that occurs on lysine residues. It plays an irreplaceable role in various cellular functions. Therefore, identification of glutarylation sites is significant for understanding the molecular mechanism of glutarylation. In this study, we proposed a method named DEXGB_Glu to identify lysine glutarylation sites using XGBoost as classifier which was optimized by differential evolution algorithm. Aiming at the imbalance between positive samples and negative samples, Borderline-SMOTE method was employed to synthesize positive samples, increasing their amount equal to negative samples. Then, Tomek links technique was applied to filter out noise data. Analysis of this method and its results showed that differential evolution algorithm obviously improved the performance and the combination of Borderline-SMOTE and Tomek links effectively solved the imbalance between positive samples and negative samples. Finally, the performance of this method was much better than other methods in prediction of glutarylation sites. The data and code are available on https://github.com/ningq669/DEXGB_Glu.

3.
Huan Jing Ke Xue ; 42(7): 3118-3126, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212637

RESUMO

Ozone pollution has recently become a severe air quality issue in the Beijing-Tianjin-Hebei region. Due to the lack of a precursor emission inventory and complexity of physical and chemical mechanism of ozone generation, numerical modeling still exhibits significant deviations in ozone forecasting. Owing to its simplicity and low calculation costs, the time series analysis model can be effectively applied for ozone pollution forecasting. We conducted a time series analysis of ozone concentration at Shangdianzi, Baoding, and Tianjin sites. Both seasonal and dynamic ARIMA models were established to perform mid- and long-term ozone forecasting. The correlation coefficient R between the predicted and observed value can reach 0.951, and the RMSE is only 10.2 µg·m-3 for the monthly average ozone prediction by the seasonal ARIMA model. The correlation coefficient R between the predicted and observed value increased from 0.296-0.455 to 0.670-0.748, and RMSE was effectively reduced for the 8-hour ozone average predicted by the dynamic ARIMA model.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Pequim , China , Monitoramento Ambiental , Previsões , Modelos Estatísticos , Ozônio/análise
4.
Indoor Air ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34288147

RESUMO

Online measurements of indoor and outdoor ammonia (NH3 ) were conducted at a university building in Haidian District, Beijing, to investigate their variation characteristics, indoor-outdoor differences, influencing factors, and possible contribution of indoor NH3 to atmospheric NH3 . Indoor NH3 mixing ratios varied greatly among the rooms of the same building. Indoor NH3 mixing ratio peaked at 1.43 ppm in a toilet. Both indoor and outdoor NH3 mixing ratios exhibited higher values during summer and lower values during winter and correlated significantly with relative humidity and temperature. Moreover, their daily mean mixing ratios were significantly correlated with each other. But indoor and outdoor NH3 in cold months exhibited quite different diurnal variations. During the measurement period, indoor NH3 mixing ratios were substantially higher than those outdoors, by an average factor of 3.1 (1.0-6.6). This indicates that indoor NH3 could be a source of outdoor atmospheric NH3 . The contribution of indoor NH3 to atmospheric NH3 was estimated at 0.7 ± 0.5 Gg NH3 -N·a-1 , accounting for approximately 1.0 ± 0.7% of total emissions in Beijing and being comparable to industry, biomass combustion, and soil emissions, but lower than transportation emissions. The influence of COVID-19 control measures caused indoor and outdoor NH3 mixing ratios to decrease by 22.8% and 19.3%, respectively-attributable to decreased human activity and traffic flow.

5.
J Biomater Sci Polym Ed ; : 1-15, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34328067

RESUMO

This study explains the engineering of polylactide-polyethylene succinate glycol nanomaterials (NMs), to achieve superior anticancer effectiveness in prostate cancer therapy as a carriers of crizotinib (CZT) and marizomib (MAR). We have shown that the block polymers and hydrophobic drugs can be self-assembled to construct a highly stable nanocarrier with highly adaptable to support the use of cancer medicines. The Drug Release analysis revealed that the interference in the hydrophobic cores of micelles was a continuous release series. In both PC3pip and LNCAP prostate cancer cells, CZT@MAR NMs demonstrated noticeable cytotoxic effects in a dose-responsive method. In addition, morphology analysis and the AO-EB and nuclear staining assay showed a higher effectiveness in prostate cancer for nanomaterials. The polymeric nanomaterials displayed a prominent existence in the cytoplasmic cell regions, which shows a characteristic cell uptake by endocytosis. A significant apoptosis, compared to free CZT@MAR apoptosis, was found in the FITC-Annexin V/PI staining-based apoptosis analysis. In this juncture, the alternative drug delivery mechanism for the improvement of CZT@MAR chemotherapeutic effectiveness in prostate cancer chemotherapy modification PLA nanoparticles.

6.
Colloids Surf B Biointerfaces ; 205: 111903, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34144323

RESUMO

A combination of photodynamic therapy (PDT) and histone deacetylase inhibitor (HDACis) could potentiate single-mode anti-tumor activity of HDACis or PDT to inhibit tumor relapse and metastasis. However, poor solubility and heterogeneity in cellular uptake and tissue distribution hamper the dual mode antitumor effect. For a controlled drug release of photosensitizers and HDACis in cytoplasm, photosensitizer pyropheophorbide-a (Pyro) encapsulated in polymer polyethylene glycol-b-poly (asparaginyl-vorinostat) (simplified as Pyro@FPPS) are fabricated to achieve their lysosomal spatiotemporal synchronized release. With HDACis modeling PDT in vitro and in vivo, it seems that polymerized Vorinostat encapsulated photosensitizers significantly inhibited the tumor proliferation and metastasis by spatiotemporal synchronized drugs release, and Pyro@FPPS reported here reveals a promising prospect to exert drugs' synergistic effect in a spatiotemporal synchronized manner and can be an effective strategy to inhibit tumor growth, recurrence and metastasis in clinic.


Assuntos
Antineoplásicos , Fotoquimioterapia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Inibidores de Histona Desacetilases/farmacologia , Lisossomos , Fármacos Fotossensibilizantes/farmacologia , Vorinostat/farmacologia
7.
Environ Sci Pollut Res Int ; 28(39): 54551-54564, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34018103

RESUMO

The current global spirit for sustainable development has led to increased attention to reducing the use of conventional energy sources and managing the issue of climate change. Renewable (or clean) energy consumption is a key element of any country's environmental quality and sustainable economic growth. This study provides a comprehensive analysis of the impacts on clean energy consumption of common factors in pursuing a sustainability strategy, including environmental degradation (measured as carbon dioxide (CO2) emissions), clean energy technology, gross domestic product (GDP) growth, institutional quality, and globalization for a panel of European Union (EU) 28 countries in the period from 1995 to 2017. We employ two estimation techniques, continuous updating-fully modifying (CUP-FM) and continuous updating-bias correcting (CUP-BC). In addition, the study incorporates Driscoll-Kraay regression for a panel model to investigate the validity and reliability of long-term elasticities' results. The findings of long-run analyses indicate that CO2 emissions, clean energy technology, GDP growth, and globalization positively impact clean energy consumption and institutional quality negatively impacts it. Finally, the results of causality testing indicate a unidirectional causal relationship between clean energy technology and clean energy consumption and a bidirectional association between institutional quality and clean energy consumption. The study's outcomes have policy implications, especially regarding designing strategic choices to promote investment in clean energy technology to increase the use of clean energy sources and to overcome the issues of institutional quality in supporting clean energy consumption in the EU-28 countries.


Assuntos
Desenvolvimento Econômico , Políticas , Energia Renovável , União Europeia , Produto Interno Bruto , Reprodutibilidade dos Testes
8.
Drug Deliv ; 28(1): 963-972, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34036867

RESUMO

PD-1/PD-L1 blocking therapy has become one of the most promising methods in the field of tumor treatment. However, it encounters the challenge of immune escape due to the exhaustion of T cells. Studies have shown that the epigenetic regulation drug histone deacetylase inhibitor (HDACi) may be able to reverse exhausted T cells by changing the epigenetic transcription program. Therefore, the combination of epigenetic therapy and PD-1/PD-L1 blockade therapy is expected to reverse the immune escape, whereas the overriding goal should aim at the spontaneous release and synergy of PD-1/PD-L1 blocking siRNA and HDACi. In this study, we develop PDDS{polyethylene glycol-b-asparaginate(diethylenetriamine-vorinostat), (PEG-b-P[Asp(DET-SAHA)n] PPDS)}encapsulating siRNA-PD-L1to provide micelles siRNA-PD-L1-loaded micelles (siRNA@PPDS). Transmission electron microscope (TEM) images demonstrate that siRNA@PPDS micelles presented spherical morphology with a size of about 120 nm; hydrodynamic data analysis indicates pH sensitivity of siRNA@PPDS micelles. The experiments reveal that siRNA@PPDS micelles could be well uptaken by the tumor cells to silence the expression of PD-L1 protein in a dose-dependent manner; compared with the free SAHA, the SAHA-loaded micelles PPDS show higher cytotoxicity to induce tumor cell apoptosis and block cell cycle in G1 phase on melanoma-bearing mice, siRNA@PPDS has shown outstanding inhibition of tumor growth and pulmonary metastasis. By comprehensively activating the immune system, lysosome activable polymeric vorinostat encapsulating PD-L1KD for the combination therapy of PD-L1-KD and HDACIs can be an effective strategy to reverse the unresponsiveness of immune checkpoint inhibitors and a promising treatment to inhibit tumor growth, recurrence, and metastasis in clinic.

9.
Parasitol Res ; 120(5): 1627-1636, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33792812

RESUMO

Paragonimus proliferus, a lung fluke of the genus Paragonimus, was first reported in Yunnan province, China. P. proliferus can infect Sprague-Dawley (SD) rats and cause lung damage, but there is still no direct evidence of human infection. Until now, there has been a lack of studies on P. proliferus parasitism and development in mammalian lung tissue. The aim of this study was to perform transcriptomic profiling of P. proliferus at different developmental stages. SD rats were infected with P. proliferus metacercariae obtained from crabs; worms isolated from the lungs at different time points as well as metacercariae were subjected to whole transcriptome sequencing. Overall, 34,403 transcripts with the total length of 33,223,828 bp, average length of 965 bp, and N50 of 1833 bp were assembled. Comparative analysis indicated that P. proliferus, similar to other Paragonimus spp., expressed genes related to catabolism, whereas P. proliferus-specific transcripts were related to the maintenance of cellular redox homeostasis, sensitivity to bacteria, and immune response. Transcriptional dynamics analysis revealed that genes involved in the regulation of catabolism and apoptosis had stable expression over the P. proliferus life cycle, whereas those involved in development and immune response showed time-dependent changes. High expression of genes associated with immune response corresponded to that of genes regulating the sensitivity to bacteria and immune protection. We constructed a P. proliferus developmental model, including the development of the body, suckers, blood cells, reproductive and tracheal systems, lymph, skin, cartilage, and other tissues and organs, and an immune response model, which mainly involved T cells and macrophages. Our study provides a foundation for further research into the molecular biology and infection mechanism of P. proliferus.


Assuntos
Pulmão/parasitologia , Paragonimíase/patologia , Paragonimus/embriologia , Paragonimus/crescimento & desenvolvimento , Animais , Braquiúros/parasitologia , China , Perfilação da Expressão Gênica , Humanos , Estágios do Ciclo de Vida , Metacercárias/crescimento & desenvolvimento , Paragonimíase/parasitologia , Paragonimus/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Transcriptoma/genética
10.
J Cardiothorac Surg ; 16(1): 28, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741016

RESUMO

OBJECTIVE: To summarize the clinical characteristics of adult cases of paragonimiasis with lung masses as the main manifestation in Xishuangbanna, Yunnan Province, analyze the causes of misdiagnosis, and improve the levels of clinical diagnosis and treatment. METHOD: We conducted a retrospective analysis of the clinical data and diagnosis and treatment of 8 adult cases of paragonimiasis with lung masses as the main manifestation that were diagnosed in the Oncology Department of People's hospital of Xishuangbanna Dai Autonomous Prefecture from July 2014 to July 2019. RESULT: All 8 patients were from epidemic paragonimiasis areas and had a confirmed history of consuming uncooked freshwater crabs. The clinical manifestations were mainly fever, dry cough, and chest pain. The disease durations were long, and peripheral blood eosinophil counts were elevated. The cases had been misdiagnosed as pneumonia or pulmonary tuberculosis. After years of anti-inflammatory or anti-tuberculosis treatment, the symptoms had not improved significantly. Patients eventually sought treatment from the oncology department for hemoptysis. Chest computed tomography showed patchy consolidation in the lungs, with nodules, lung masses, and enlarged mediastinal lymph nodes. CONCLUSION: Paragonimiasis is a food-borne parasitic disease. Early clinical manifestations and auxiliary examination results are nonspecific. The parasite most often invades the lungs, and the resulting disease is often misdiagnosed as pneumonia, pulmonary tuberculosis, or lung cancer (Acta Trop 199: 05074, 2019). To avoid misdiagnosis, clinicians should inquire, in detail, about residence history and history of unclean food and exposure to infected water and make an early diagnosis based on the inquired information and imaging examination results. For patients who have been diagnosed with pneumonia or pulmonary tuberculosis and whose symptoms do not improve significantly after anti-inflammatory or anti-tuberculosis treatments, their epidemiological history should be traced to further conduct differential diagnosis and avoid misdiagnosis.


Assuntos
Pneumopatias Parasitárias/diagnóstico , Pulmão/diagnóstico por imagem , Paragonimíase/diagnóstico , Animais , Anticorpos Anti-Helmínticos/análise , China/epidemiologia , DNA de Helmintos/análise , Diagnóstico Diferencial , Erros de Diagnóstico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Incidência , Pulmão/parasitologia , Pneumopatias Parasitárias/epidemiologia , Pneumopatias Parasitárias/parasitologia , Masculino , Pessoa de Meia-Idade , Paragonimíase/tratamento farmacológico , Paragonimíase/parasitologia , Paragonimus/genética , Paragonimus/imunologia , Estudos Retrospectivos , Tórax/patologia , Tomografia Computadorizada por Raios X
11.
Eur J Med Chem ; 217: 113363, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33744687

RESUMO

The combination of photodynamic therapy (PDT) and chemotherapy is a prospective strategy to improve antitumor efficacy. Herein, a series of novel cytotoxic chlorin-based derivatives as dual photosensitizers (PSs) and histone deacetylase inhibitors (HDACIs) were synthesized and investigated for biological activity. Among them, compound 15e showed definite HDAC2 and 10 inhibitory activities by up-regulating expression of acetyl-H4 and highest phototoxicity and dark-toxicity, which was more phototoxic than Talaporfin as a PS while with stronger dark-toxicity compared to vorinostat (SAHA) as a HDACI. The biological assays demonstrated that 15e was liable to enter A549 cells and localized in mitochondria, lysosomes, golgi and endoplasmic reticulum (ER) etc. multiple organelles, resulting in higher cell apoptosis rate and ROS production compared to Talaporfin. Moreover, it could induce tumor cell autophagy as a dual PS and HDACI. All results suggested that compound 15e could be applied as a potential dual cytotoxic drug for PDT and chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Estrutura Molecular , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfirinas/síntese química , Porfirinas/química , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
12.
Environ Sci Technol ; 55(6): 3568-3581, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33656863

RESUMO

Peroxyacetyl nitrate (PAN) is an important indicator for photochemical pollution, formed similar to ozone in the photochemistry of certain volatile organic compounds (VOCs) in the presence of nitrogen oxides, and has displayed surprisingly high concentrations during wintertime that were better correlated to particulate rather than ozone concentrations, for which the reasons remained unknown. In this study, wintertime observations of PAN, VOCs, PM2.5, HONO, and various trace gases were investigated to find the relationship between aerosols and wintertime PAN formation. Wintertime photochemical pollution was affirmed by the high PAN concentrations (average: 1.2 ± 1.1 ppb, maximum: 7.1 ppb), despite low ozone concentrations. PAN concentrations were determined by its oxygenated VOC (OVOC) precursor concentrations and the NO/NO2 ratios and can be well parameterized based on the understanding of their chemical relationship. Data analysis and box modeling results suggest that PAN formation was mostly contributed by VOC aging processes involving OH oxidation or photolysis rather than ozonolysis pathways. Heterogeneous reactions on aerosols have supplied key photochemical oxidants such as HONO, which produced OH radicals upon photolysis, promoting OVOC formation and thereby enhancing PAN production, explaining the observed PM2.5-OVOC-PAN intercorrelation. In turn, parts of these OVOCs might participate in the formation of secondary organic aerosol, further aggravating haze pollution as a feedback. Low wintertime temperatures enable the long-range transport of PAN to downwind regions, and how that will impact their oxidation capacity and photochemical pollution requires further assessment in future studies.


Assuntos
Poluentes Atmosféricos , Ozônio , Aerossóis , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Ozônio/análise , Ácido Peracético/análogos & derivados
13.
Zhongguo Zhong Yao Za Zhi ; 46(2): 320-332, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645118

RESUMO

With the increasing incidence of hepatobiliary diseases, it is particularly important to understand the role of molecular, cellular and physiological factors in the clinical diagnosis and treatment with traditional Chinese medicine(TCM) in the development of liver disease. Appropriate animal models can help us identify the possible mechanisms of relevant diseases. Danio rerio(zebrafish) model was traditionally used to study embryonic development, and has been gradually used in screening and evaluation of liver diseases and relevant drug in recent years. Zebrafish embryos develop rapidly and the digestive organs of 5-day-old juvenile fish are all mature. At this stage, they may develop hepatobiliary diseases induced by developmental defects or compounds. Zebrafish liver is similar to human liver in cell composition, function, signal transduction, response to injury and cell process mediating liver disease. Furthermore, due to the high conservation of genes and proteins between humans and zebrafish, zebrafish becomes an alternative system for studying basic mechanisms of liver disease. Therefore, genetic screening could be performed to identify new genes involving specific disease processes, and chemical screening could be made for drugs in specific processes. This paper briefly introduced the experimental properties of zebrafish as model system, emphasized the study progress of zebrafish models for pathological mechanism of liver diseases, especially fatty liver, and drug screening and evaluation, so as to provide ideas and techniques for the future liver toxicity assessment of TCM.


Assuntos
Hepatopatias , Peixe-Zebra , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Fígado , Hepatopatias/genética , Medicina Tradicional Chinesa , Peixe-Zebra/genética
14.
World J Surg Oncol ; 19(1): 44, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563277

RESUMO

BACKGROUND: Neoadjuvant chemotherapy is an important part of the comprehensive treatment of advanced gastric cancer (GC). The effect of neoadjuvant chemotherapy plays a key role in the prognosis of GC patients. Pathological response can represent the effect of neoadjuvant chemotherapy. However, evidence focused on pathological response and associated clinicopathological factors in GC patients is quite little. In this retrospective study, the clinicopathological factors affecting the effect of neoadjuvant chemotherapy in GC patients were investigated, and suggestions were proposed to improve the effect of neoadjuvant chemotherapy on GC. METHODS: Retrospective analysis was performed on GC patients who received radical surgery after neoadjuvant chemotherapy from February 2016 to December 2019 at Peking Union Medical College Hospital. Relevant clinicopathological data was collected to analyze the factors influencing the effect of neoadjuvant chemotherapy. Chi-square test was used for univariate analysis. Logistic regression was used for multivariate analysis. Receiver operating characteristic curve (ROC) was used to determine the cutoff value of variables which significantly influenced the effect of neoadjuvant chemotherapy. RESULTS: A total of 203 GC patients were included in the study. Analyses showed that patients < 60 years old (OR = 1.840 [1.016-3.332], P = 0.044), histological type of poor differentiation or signet-ring cell carcinoma (OR = 2.606 [1.321-5.140], P = 0.006), and weight loss during neoadjuvant chemotherapy (OR = 2.110 [1.161-3.834], P = 0.014) were independent risk factors for neoadjuvant chemotherapy effect. In ROC analysis of weight change and neoadjuvant chemotherapy effect, area under the curve (AUC) was 0.593 (P = 0.024) and cutoff value of weight change was - 2.95%. Chi-square test showed that patients without weight loss during neoadjuvant chemotherapy had a higher rate of oral nutritional supplement (ONS) than patients with weight loss (P = 0.039). CONCLUSIONS: Patients <60 years old, histological type of poor differentiation or signet-ring cell carcinoma, and weight loss during neoadjuvant chemotherapy were independent risk factors for neoadjuvant chemotherapy effect in GC patients. Patients with weight loss > 2.95% during neoadjuvant may have a worse chemotherapy effect. Timely nutritional support such as ONS to maintain patients' body weight is crucial for improving the effect of neoadjuvant chemotherapy.


Assuntos
Carcinoma de Células em Anel de Sinete , Neoplasias Gástricas , Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico
15.
Nutrition ; 85: 111135, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33556785

RESUMO

OBJECTIVES: The influence of body composition on clinical outcomes in individuals with gastric cancer (GC) undergoing radical gastrectomy after neoadjuvant treatment (NT) remains unclear. The purpose of this retrospective study was to investigate the association between body composition before NT or after NT and clinical outcomes in individuals with GC receiving multimodal treatments. METHODS: This retrospective study included individuals with GC who received NT followed by radical gastrectomy between January 2016 and December 2018. Skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured by cross-sectional areas at the level of third lumbar vertebra based on single-slice computed tomography scan prior to NT and prior to the surgical operation. Sarcopenia, high VAT, and high SAT were defined using cutoff points of skeletal muscle index, visceral fat area, and subcutaneous fat area. Univariate and multivariate analyses were performed to evaluate risk factors of NT-related adverse events, postoperative complications and predictors of long-term survival. RESULTS: A total of 110 individuals with GC were enrolled in this study. Sarcopenia was present in 62.7% of them before NT and in 56.4% after NT. Sarcopenia before NT was associated with more NT-related adverse events (odds ratio, 2.901; 95% confidence interval [CI], 1.205-6.983; P = 0.018). High VAT after NT (≥106 cm2) was associated with an increasing incidence of postoperative complications (odds ratio, 4.261; 95% CI, 1.332-13.632; P = 0.015). No body-composition parameter was relevant to tumor pathologic response to NT. As for long-term survival, poor overall survival was associated with both low VAT before NT (<120 cm2; hazard ratio [HR], 2.542; 95% CI, 1.111-5.817; P = 0.027) and low SAT after NT (<99.5 cm2; HR, 2.743; 95% CI, 1.248-6.027; P = 0.012). Similarly, shorter disease-free survival was associated with low VAT before NT (<120 cm2; HR, 2.502; 95% CI, 1.222-5.124; P = 0.012) and low VAT after NT (<106 cm2; HR, 2.505; 95% CI, 1.172-5.358; P = 0.018). CONCLUSIONS: Body composition measured by computed tomography could predict NT-related adverse events, postoperative complications, and long-term survival in multimodal treatments for GC. More meaningfully, adipose-tissue status has significant prognostic value for individuals with advanced GC.


Assuntos
Neoplasias Gástricas , Composição Corporal , Gastrectomia/efeitos adversos , Humanos , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
16.
Brief Bioinform ; 22(5)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-33454736

RESUMO

Haploinsufficiency, wherein a single allele is not enough to maintain normal functions, can lead to many diseases including cancers and neurodevelopmental disorders. Recently, computational methods for identifying haploinsufficiency have been developed. However, most of those computational methods suffer from study bias, experimental noise and instability, resulting in unsatisfactory identification of haploinsufficient genes. To address those challenges, we propose a deep forest model, called HaForest, to identify haploinsufficient genes. The multiscale scanning is proposed to extract local contextual representations from input features under Linear Discriminant Analysis. After that, the cascade forest structure is applied to obtain the concatenated features directly by integrating decision-tree-based forests. Meanwhile, to exploit the complex dependency structure among haploinsufficient genes, the LightGBM library is embedded into HaForest to reveal the highly expressive features. To validate the effectiveness of our method, we compared it to several computational methods and four deep learning algorithms on five epigenomic data sets. The results reveal that HaForest achieves superior performance over the other algorithms, demonstrating its unique and complementary performance in identifying haploinsufficient genes. The standalone tool is available at https://github.com/yangyn533/HaForest.

17.
J Ethnopharmacol ; 271: 113818, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33465444

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ranunculus japonicus Thunb. (short for R. japonicus) is a topically applied herb with the activities of removing jaundice, nebula and edema, preventing malaria, stopping asthma, promoting diuresis and relieving pain. It was firstly recorded in Zhouhou Beiji Fang and has been used for the treatment of malaria, ulcers, carbuncle, jaundice, migraine, stomachache, toothache and arthritis for over 1800 years. AIM OF THE STUDY: This study aimed to uncover the potentially effective components of R. japonicus and the pharmacological mechanisms against rheumatoid arthritis (RA) by combing LC-MS and network pharmacology. MATERIALS AND METHODS: Firstly, the chemical constituents of R. japonicus were qualitatively identified by UPLC-ESI-LTQ-Orbitrap MS. Then we performed target prediction by PharmMapper, protein-protein interaction (PPI) analysis via String, GO and KEGG pathway enrichment analysis by DAVID and constructed the compound-target-pathway network using Cytoscape. Thirdly, crucial compounds in the network were quantitatively analyzed to achieve quality control of R. japonicus. Finally, the pharmacological activities of R. japonicus and two potentially bioactive ingredients were validated in RA-FLSs (Rheumatoid Arthritis Fibroblast-like Synoviocytes) in vitro. RESULTS: Overall fifty-four ingredients of R. japonicus were identified and forty-five components were firstly discovered in R. japonicus. Among them, twenty-seven validated compounds were predicted to act on twenty-five RA-related targets and they might exhibit therapeutic effects against RA via positive regulation of cell migration, etc. Nine potentially bioactive components of R. japonicus which played important roles in the compound-target-pathway network were simultaneously quantified by an optimized UPLC-ESI-Triple Quad method. In vitro, compared to control group, R. japonicus extract, berberine and yangonin significantly inhibited the migration capacity of RA-FLSs after 24 h treatment. CONCLUSION: This study clarified that R. japonicus and the bioactive ingredients berberine and yangonin might exert therapeutic actions for RA via suppressing the aggressive phenotypes of RA-FLSs through combined LC-MS technology and network pharmacology tools for the first time. The present research provided deeper understanding into the chemical profiling, pharmacological activities and quality control of R. japonicus and offered reference for further scientific research and clinical use of R. japonicus in treating RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Farmacologia/métodos , Ranunculus/química , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida , Fibroblastos/efeitos dos fármacos , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Mapas de Interação de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sinoviócitos/efeitos dos fármacos , Espectrometria de Massas em Tandem , Cicatrização/efeitos dos fármacos
18.
J Hum Nutr Diet ; 34(3): 585-594, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33491826

RESUMO

BACKGROUND: The influence of body composition changes during neoadjuvant treatment (NT) on long-term survival in patients with gastric cancer (GC) undergoing radical gastrectomy remains unclear. The present study aimed to explore the association between changes in body composition during NT and survival in patients with GC. METHODS: GC patients treated with NT and radical gastrectomy between 2015 and 2018 were included in this retrospective study. Skeletal muscle mass, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by computer tomography before and after NT. Body composition changes during NT were compared with Kaplan-Meier curves. Univariate and multivariate regression analyses were applied to determine the predictors of overall survival (OS) and disease-free survival (DFS). RESULTS: In total, 157 GC patients were studied. A marked loss of adipose tissue was associated with poor nutritional status. The median follow-up time for all patients was 25 months. Patients with marked VAT loss (≥ 35.7%) during NT had significantly shorter OS (p = 0.028) and DFS (p = 0.03). Similarly, poorer OS (p = 0.033) and DFS (p = 0.003) were observed in patients with marked SAT loss (≥ 30.1%) during NT. Changes in skeletal muscle mass and body weight during NT were not associated with survival. Marked VAT loss accompanied by marked SAT loss was an independent predictor of OS (hazards ratio = 2.447; p = 0.045) and DFS (hazards ratio = 2.674; p = 0.018). CONCLUSIONS: Patients with locally advanced GC have a worse survival when they experienced marked loss of adipose tissue during NT.

19.
Angew Chem Int Ed Engl ; 60(10): 5512-5518, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33206427

RESUMO

We describe herein the assembly of the cis-decalin framework through radical cyclization initiated by metal-catalyzed hydrogen atom transfer (MHAT), further applied it in the asymmetric synthesis of dankasterones A and B and periconiastone A. Position-selective C-H oxygenation allowed for installation of the necessary functionality. A radical rearrangement was adopted to create 13(14→8)abeo-8-ergostane skeleton. Interconversion of dankasterone B and periconiastone A was realized through biomimetic intramolecular aldol and retro-aldol reactions. The MHAT-based approach, serves as a new dissection means, is complementary to the conventional ways to establish cis-decalin framework.

20.
Ann Transl Med ; 8(19): 1248, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33178780

RESUMO

Retroperitoneal liposarcoma is a rare malignancy derived from adipocytes. They can grow to large sizes before inducing clinical symptoms. Giant retroperitoneal liposarcoma with a diameter over 30 centimeters is extremely rare. So far, only 13 cases of giant retroperitoneal liposarcoma with a diameter greater than 30 cm have been reported. There is very little experience in the treatment of these bulky tumors. Herein, we report a 65-year-old male patient diagnosed with giant retroperitoneal liposarcoma. The patient underwent successful complete surgical resection. The tumor was found to occupy almost the entire abdominal cavity, measuring 37.0 cm × 32.0 cm × 26.5 cm in size and 21.0 kg in weight. Histopathological analysis indicated a grade I, well-differentiated liposarcoma. The patient was discharged uneventfully, and no sign of recurrence was observed at 12-month follow-up. Moreover, we reviewed 13 literatures in English published on PubMed database regarding retroperitoneal liposarcoma greater than 30 cm in diameter. The analysis suggests that size alone should not be considered as a contraindication to surgical resection. Combined resection of adjacent organs is necessary if local invasion is confirmed. The role of adjuvant radio or chemotherapy remains controversial. Thorough evaluation on the extent of resection should be made to minimize post-surgery decline in quality of life.

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