RESUMO
Pulmonary arterial hypertension (PAH) is a rare but fatal disease characterized by elevated pulmonary vascular resistance and increased pressure in the distal pulmonary arteries. Systematic analysis of the proteins and pathways involved in the progression of PAH is crucial for understanding the underlying molecular mechanism. In this study, we performed tandem mass tags (TMT)-based relative quantitative proteomic profiling of lung tissues from rats treated with monocrotaline (MCT) for 1, 2, 3 and 4 weeks. A total of 6759 proteins were quantified, among which 2660 proteins exhibited significant changes (p-value < 0.05, fold change < 0.83 or >1.2). Notably, these changes included several known PAH-related proteins, such as Retnla (resistin-like alpha) and arginase-1. Furthermore, the expression of potential PAH-related proteins, including Aurora kinase B and Cyclin-A2, was verified via Western blot analysis. In addition, we performed quantitative phosphoproteomic analysis on the lungs from MCT-induced PAH rats and identified 1412 upregulated phosphopeptides and 390 downregulated phosphopeptides. Pathway enrichment analysis revealed significant involvement of pathways such as complement and coagulation cascades and the signaling pathway of vascular smooth muscle contraction. Overall, this comprehensive analysis of proteins and phosphoproteins involved in the development and progression of PAH in lung tissues provides valuable insights for the development of potential diagnostic and treatment targets for PAH.
Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Ratos , Animais , Hipertensão Pulmonar/metabolismo , Fosfopeptídeos , Proteômica , Pulmão/metabolismo , Artéria Pulmonar/metabolismo , Hipertensão Pulmonar Primária Familiar , Modelos Animais de DoençasRESUMO
BACKGROUND: Cancer therapy has evolved from non-specific cytotoxic agents to a selective, mechanism-based approach that includes targeted agents and immunotherapy. Although the response to targeted therapies for unresectable hepatocellular carcinoma (HCC) is acceptable with the improved survival, the high tumor recurrence rate and drug-related side effects continue to be problematic. Given that immune checkpoint inhibitor alone are not robust enough to improve survival in unresectable HCC, growing evidence supports the combination of targeted therapy and immunotherapy with synergistic effect. METHODS: Online databases including PubMed, EMBASE, Cochrane Library, and Web of Science were searched for the studies that compared targeted monotherapy with the combination therapy of targeted drug and checkpoint inhibitors in unresectable HCC patients. Eligibility criteria were the presence of at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (version 1.1) for unresectable HCC patients, an Eastern Cooperative Oncology Group performance status of 0-2, and a Child-Pugh score ≤ 7. Outcome measurements include overall survival (OS), progression-free survival (PFS), and treatment-related adverse event (TRAE). RESULTS: Three phase II/III randomized controlled trials were included in this study. The pooled results showed that combination therapy significantly improved survival than targeted monotherapy, in terms of OS (hazard ratio (HR) = 0.67; 95% confidence interval [CI]: 0.50-0.91) and PFS (HR = 0.58; 95% CI: 0.51-0.67), respectively. In the incidence of grade 3-5 TRAEs, the combination therapy was significantly higher than targeted monotherapy (odds ratio = 1.98; 95% CI: 1.13-3.48). CONCLUSION: For unresectable HCC, combined targeted drug and immunotherapy significantly improved survival compared with targeted monotherapy. However, the incidences of AEs of combinational therapy were higher than targeted monotherapy.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Inibidores de Checkpoint Imunológico , Recidiva Local de Neoplasia/tratamento farmacológico , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Fatores Imunológicos/uso terapêutico , Citotoxinas , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase II como AssuntoRESUMO
Vinyl chloride monomer (VCM) is classified as group 1 carcinogenic to humans by the International Agency for Research for Cancer (IARC). In 2012, USEPA promulgated a new VCM emission standard as part of National Emission Standards for Hazardous Air Pollutants (NESHAP) for polyvinyl chloride (PVC) and copolymer plants. The standard was set by benchmarking of peer plants with maximum achievable control technology (MACT). This study performs an emission assessment of a world-class PVC plant in Taiwan according to the MACT analysis. The emission data obtained were then benchmarked with baseline emission estimates of 15 PVC plants in the USA. Results of this study show seven types of VCM emissions: stripped resin of suspension/dispersion, wastewater, process vent, heat-exchange system, storage tank, equipment leaks, and other sources (gasholder). All the emission factors are complied with their MACT emission limitations (MEL) and ranked either #1 or #2 among the 15 plants. They are also summed and benchmarked against the production capacity of each plant, showing a negative power function with a fair correlation (R2 = 0.73). Among seven types of emissions, stripped resin contributes the highest (51.7%) by average emission factor of the 15 plants plus this study plant.
Assuntos
Poluentes Ocupacionais do Ar , Monitoramento Ambiental , Cloreto de Vinil , Benchmarking , Indústria Química , Humanos , Cloreto de Polivinila , Taiwan , Estados UnidosRESUMO
Intensive care unit (ICU)-acquired weakness is a common neuromuscular complication of critical illness that is considered to be associated with prolonged duration on mechanical ventilation and systemic inflammatory response syndrome. In addition, nutrition and metabolic alternations, which are commonly seen in patients in the ICU, may further accelerate muscle wasting and increase the incidence of ICU-acquired weakness. The clinical features of ICU-acquired weakness include acute generalized muscle weakness that develops after the onset of critical illness. Diaphragmatic dysfunction, post-extubation dysphagia, and functional decline also are common in patients with ICU-acquired weakness. As the recovery of these physical functions is lengthy and difficult, a multidisciplinary team management is recommended. This mini-review was conducted to provide a scientific overview for ICU-acquired weakness, including its definition, etiology, diagnosis/screening, impacts, and potential intervention strategies. We hope that increasing the understanding of frontline staff will promote the timely planning and implementation of related screenings and interventions to enhance the functional recovery of patients receiving care in the ICU.
Assuntos
Cuidados Críticos , Unidades de Terapia Intensiva , Debilidade Muscular/epidemiologia , Estado Terminal , Humanos , Incidência , Respiração ArtificialRESUMO
With the global land use/land cover (LULC) and climate change, the ecological resilience (ER) in typical Karst areas has become the focus of attention. Its future development trend and its spatial response to natural and anthropogenic factors are crucial for understanding the changes of ecologically fragile areas to human behavior. However, there is still a lack of relevant quantitative research. The study systematically analyzed the characteristics of LULC changes in Southwest China with typical Karst over the past 20 years. Drawing on the landscape ecology research paradigm, a potential-elasticity-stability ER assessment model was constructed. Revealing the characteristics and heterogeneity of the spatial distribution, annual evolution, and development trend of ER in the past and under different scenarios of shared socioeconomic pathways and representative concentration pathways (SSP-RCP) in the future. In addition, the spatial econometric model was utilized to reveal the spatial effect response mechanism of ER, and adaptive development strategies were proposed to promote the sustainable development of Southwest China. The study found that : (1) In the past 20 years, the LULC in Southwest China showed an accelerated change trend, the ER decreased declined in general, and there was significant spatial heterogeneity, showing the spatial distribution pattern of "west is larger than east, south is larger than north, and reduction in the west was slower than that in the east." (2) Under the same SSP scenario, with the increase of RCP emission concentration, the area of the lowest-resilience increased significantly, and the area of the highest-resilience decreased. (3) The woodland was the largest contributor to ER per unit area in the Southwest China, and grassland was the main LULC type, which had a prominent impact on the ER of the study area. (4) The average precipitation and the normalized difference vegetation index (NDVI) were significant natural drivers of ER in the study area, and the economic growth, innovation, and optimization of industrial structure contributed to the ER of Southwest China. Overall, the integration of quantitative assessment and multi-scenario-based modeling not only provides new perspectives for understanding the pattern of change and response mechanisms, but also provides valuable references for other typical Karst regions around the world to achieve sustainable development.
RESUMO
Background: Radiation-induced hemorrhagic cystitis (RHC) is a chronic inflammatory disease in patients undergoing radiation therapy that causes a cluster of symptoms which may have a latent period of months to years. The current non-invasive treatments include drug treatment and hyperbaric oxygen therapy (HBOT), which has been widely applied for RHC so far but with limited evidence. Thus, we conducted a systematic review and meta-analysis to clarify the effects and safety of HBOT for RHC. Methods: A systematic review and meta-analysis were utilized, searching in the databases of Embase, Pubmed, and Web of Science. The primary endpoint of the present study was complete remission of hematuria. The meta-analysis was conducted using a random effects model, and a pooled odds ratio with 95% CI was calculated. Results: A total of 317 studies were searched and fourteen articles with 556 patients were collected. The results showed that a total of 500 patients (89.9%) had symptom improvement, and the pooled results demonstrated that 55% of patients with HBOT had complete remission of hematuria (95% CI 51-59%). Conclusions: A significant improvement of symptoms when treated with HBOT was shown in this meta-analysis for patients with RHC.
RESUMO
AIM: This study aims to explore the effects of finite element biomechanical properties of different methods in the treatment of osteoporotic thoracolumbar fractures. METHODS: Based on the ultra-thin computed tomography scan data of a volunteer's thoracolumbar spine, the finite element method was used to simulate the treatment of osteoporotic thoracolumbar fracture. Spiral computed tomography scanning was used to obtain images of the thoracolumbar region, which was then imported into Mimics software to obtain the three-dimensional geometric model. The finite element model of normal T11 - L2 segment was established by finite element software Abaqus and the validity of the model loading was verified. The finite element model of T11 vertebral compression fracture was established based on normal raw data. The clinical overextension reduction manipulation was simulated by different treatment methods and the changes in stress and displacement in different parts of injured vertebrae were analyzed. RESULTS: An effective finite element model of T11-L2 segment was established. The maximum stress, axial compression strength, axial compression stiffness, and transverse shear stiffness were significantly better in the percutaneous kyphoplasty and percutaneous vertebroplasty treatment group than in the conservative treatment group and open treatment group (P < 0.05). Additionally, there was no significant difference between the open treatment group and conservative treatment group, or between the PKP and PVP treatment group. CONCLUSION: Percutaneous vertebroplasty and percutaneous kyphoplasty not only met the requirements of normal functional kinematics of thoracolumbar spine, but also restored the stability of thoracolumbar spine. They had good biomechanical properties and remarkable application effects. The application of finite element analysis can help select a scientific, reasonable, and effective treatment scheme for the clinical diagnosis and treatment of osteoporotic thoracolumbar fractures.
Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Análise de Elementos Finitos , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Vértebras Lombares/diagnóstico por imagem , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/diagnóstico por imagemRESUMO
Previous studies have found that the emotion of anxiety in adults is easily influence by negative stimuli However, few studies have explored the effect of stimulus types on working memory performance and cognitive processing of adults with anxiety. This study aimed to explore the effects of anxiety on affective working memory and the role of stimulus types and valences on affective working memory performance. Forty adults were recruited for the experiment and were divided into two groups according to their anxiety levels. The valence and type of stimulus were manipulated in a memory recognition experiment. The results indicated that individuals with anxiety performed poorer when subjected to positive stimuli than for neutral and negative stimuli, whereas healthy adults exhibited the opposite. Furthermore, participants outperformed on affective pictures than affective words, but the effect size of the words was larger than that of the pictures for the difference between the valence and anxiety groups. This study highlights the differences in affective working performance across stimulus types and valences between healthy adults and adults with anxiety. The findings clarified the effect of positive valence and affective words on the affective working memory processing mechanism in adults with anxiety.
RESUMO
In order to find the compound basis of Phlomis younghusbandii Mukerjee that related to pharmacodynamic action, various chromatographic techniques were used to separate and purify the constituents of this plant, and physicochemical and spectral data were used to identify the structures of obtained compounds. A new furanolabdane diterpene glycoside, named as phlomisoside F, was isolated and identified, which was 15,16-epoxy-8(9),13(16), 14-labdatrien-7-ketone-19-oic acid-beta-D-glucopyranosyl ester.
Assuntos
Diterpenos/isolamento & purificação , Glucosídeos/isolamento & purificação , Glicosídeos/isolamento & purificação , Phlomis/química , Diterpenos/química , Glucosídeos/química , Glicosídeos/química , Estrutura Molecular , Tubérculos/química , Plantas Medicinais/químicaRESUMO
The use of selected Saccharomyces cerevisiae PS7314, Lactobacillus rossiae NOS7307, Lactobacillus brevis NOS7311, and Lactobacillus plantarum NOS7315 as mono-culture or co-culture for production of sourdoughs, their breads showed different physical and organoleptic properties. The pH of breads fermented with sourdoughs incubated with mono-culture or co-culture all decreased. An opposite trend was found for TTA. The use of single lactobacillus for the dough fermentation decreased the specific volume of bread, which was 4.15-19.10% lower than that of control bread (CB). However, the synergetic fermentation helped the improvement of bread quality. Compared to CB, the mixed culture 4 sourdough remarkably decreased the hardness by 52.08%, increased the specific volume by 5.29%, improved porosity of final product by 24.90%, and gave a preferable sensory characteristic to bread. Thus, the MC4 could be recommended for replacing spontaneous sourdough for improving the quality of bread.
Assuntos
Pão/análise , Pão/microbiologia , Fenômenos Físicos , Sensação , Leveduras/metabolismo , Fermentação , Especificidade da EspécieRESUMO
Patrinia villosa (Thunb. ) Juss. is a Chinese folk medicine, in order to find the material basis that were related to anti-inflammation pharmacodynamic action, we investigated for chemical constituents by chemical and spectroscopic analysis. By phytochemical research, 9 compounds were isolated from the acetic acid ethyl ester & N-Butanol of P. villosa and identified 7 compounds (beta-sitosterol, Villosol, Quercetin, Ferulic acid, Ursolic acid, beta-daucosterol, Rutin), and three compounds (Ferulic acid, Ursolic acid and Rutin) are firstly obtained from P. villosa.