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BACKGROUND: CC chemokine receptor 5 (CCR5) has been demonstrated to be correlated to activation of pro-inflammatory immune cells and tissue injury. This study focused on the role of CCR5 in myocardial injury in rats with diabetic cardiomyopathy (DCM) and the mechanism of action. METHODS: A rat model of DCM was induced by streptozotocin (STZ). CCR5 was knocked down in rats to determine its role in myocardial injury and immune cell infiltration. The upstream regulators of CCR5 were bioinformatically predicted and the binding between nuclear receptor subfamily 4 group A member 2 (NR4A2) and CCR5 was validated. The portion of M1 and M2 macrophages in tissues was determined by flow cytometry or double-labeling immunofluorescence. Rat bone marrow mononuclear cells (BMMCs) were treated with granulocyte/macrophage colony stimulating factor (GM-CSF/M-CSF) and co-cultured with H9C2 cells for in vitro experiments. RESULTS: STZ-treated rats had impaired cardiac function and increased levels of creatine kinase-MB, cardiac troponin I and lactate dehydrogenase. CCR5 inhibition significantly alleviated myocardial injury in rats and reduced the portion of M1 macrophages in rat cardiac tissues. NR4A2, which could suppress CCR5 transcription, was poorly expressed in rats with DCM. NR4A2 overexpression played a similar myocardium-protective role in rats. In vitro, overexpression of NR4A2 induced M2 polarization of macrophages, which protected the co-cultured H9C2 cells from high glucose-induced damage, but the protective role was blocked after CCR5 overexpression. CONCLUSION: This study demonstrated that NR4A2 suppresses CCR5 expression and promotes M2 polarization of macrophages to alleviate cardiomyocyte loss and myocardial injury.
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Cardiomiopatias Diabéticas , Macrófagos , Miócitos Cardíacos , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares , Receptores CCR5 , Transcrição Gênica , Animais , Masculino , Linhagem Celular , Técnicas de Cocultura , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/imunologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Modelos Animais de Doenças , Regulação para Baixo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Miócitos Cardíacos/imunologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Fenótipo , Ratos Sprague-Dawley , Receptores CCR5/genética , Receptores CCR5/metabolismo , Transdução de SinaisRESUMO
Recent findings indicate that air pollution contributes to the onset and advancement of chronic obstructive pulmonary disease (COPD). Nevertheless, there is insufficient research indicating that air pollution is linked to COPD in the region of inland northwest China. Daily hospital admission records for COPD, air pollutant levels, and meteorological factor information were collected in Jiuquan for this study between 1 January 2018 and 31 December 2019. We employed a distributed lag non-linear model (DLNM) integrated with the generalized additive model (GAM) to assess the association between air pollution and hospital admissions for COPD with single lag days from lag0 to lag7 and multiday moving average lag days from lag01 to lag07. For example, the pollutant concentration on the current day was lag0, and on the prior 7th day was lag7. The present and previous 7-day moving average pollutant concentration was lag07. Gender, age, and season-specific stratified analyses were also carried out. It is noteworthy that the delayed days exhibited a different pattern, and the magnitude of associations varied. For NO2 and CO, obvious associations with hospitalizations for COPD were found at lag1, lag01-lag07, and lag03-lag07, with the biggest associations at lag05 and lag06 [RR = 1.015 (95%CI: 1.008, 1.023) for NO2, RR = 2.049 (95%CI: 1.416, 2.966) for CO], while only SO2 at lag02 was appreciably linked to hospitalizations for COPD [1.167 (95%CI: 1.009, 1.348)]. In contrast, short-term encounters with PM2.5, PM10, and O3 were found to have no significant effects on COPD morbidity. The lag effects of NO2 and CO were stronger than those of PM2.5 and PM10. Males and those aged 65 years or older were more vulnerable to air pollution. When it came to the seasons, the impacts appeared to be more pronounced in the cold season. In conclusion, short-term encounters with NO2 and CO were significantly correlated with COPD hospitalization in males and the elderly (≥65).
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Optimizing the wind farm layout requires accurately quantifying the wind-turbine wake distribution to minimize interference between wakes. Thus, the accuracy of wind turbine wake superposition models is critical. The sum of squares (SS) model is currently touted as the most accurate, but its application in engineering is hampered by its overestimation of the velocity deficit of the mixed wake. Therefore, previous work relied on approximate power calculations for performing optimization. The physical meaning of the SS model is unclear, which makes optimization difficult. In this study, a univariate linear correction idea is proposed based on the linear increase phenomenon of the SS method error. The unknown coefficients are obtained by fitting experimental data. The results demonstrate that the proposed method can accurately quantify the full-wake two-dimensional distribution of the mixed wake.
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Introduction: Lyophyllum decastes (Fr.) Singer polysaccharides (LDSPs) have been verified to possess strong biological properties. However, the effects of LDSPs on intestinal microbes and their metabolites have rarely been addressed. Methods: The in vitro-simulated saliva-gastrointestinal digestion and human fecal fermentation were used to evaluate the effects of LDSPs on non-digestibility and intestinal microflora regulation in the present study. Results: The results showed a slight increase in the content of the reducing end of the polysaccharide chain and no obvious change in the molecular weight during in vitro digestion. After 24 h in vitro fermentation, LDSPs were degraded and utilized by human gut microbiota, and LDSPs could be transformed into short-chain fatty acids leading to significant (p < 0.05) decrease in the pH of the fermentation solution. The digestion did not remarkably affect the overall structure of LDSPs and 16S rRNA analysis revealed distinct shifts in the gut microbial composition and community diversity of the LDSPs-treated cultures, compared with the control group. Notably, the LDSPs group directed a targeted promotion of the abundance of butyrogenic bacteria, including Blautia, Roseburia, and Bacteroides, and an increase in the n-butyrate level. Discussion: These findings suggest that LDSPs might be a potential prebiotic to provide a health benefit.
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Xixin-Ganjiang Herb Pair (XGHP), a classic combination treatment to warm the lungs and dissolve phlegm, is widely used in the treatment of various pulmonary diseases. Chronic obstructive pulmonary disease (COPD) refers to a group of chronic obstructive airway diseases that can seriously harm human health. However, the effective components, targets, and pathways that underlie XGHP in the treatment of COPD remain unclear. Therefore, this study initially identified the effective components of XGHP through the use of UPLC-MS/MS and pharmacologic methods of traditional Chinese medicine. Secondly, transcriptomic analysis of the lung tissues of rats revealed the pharmacodynamic transcripts of each group, and metabolomics analysis revealed the differential metabolites associated with XGHP treatment. Finally, molecular docking of effective components with transcriptome genes was performed and western blotting was performed in order to determine the expression of related proteins in rat lung tissue. Overall, 30 effective components of XGHP were identified, including L-asarinin, 6-gingerol, sesamin, kaempferol, and quercetin. Transcriptomic studies demonstrated that expression of 386 genes recovered after XGHP treatment, and that they were mainly enriched in the oxidative phosphorylation and AMPK signaling pathways. According to the metabolomics studies, expression of eight metabolites differed between the COPD and the XGHP groups. These metabolites were mainly involved the biosynthesis of unsaturated fatty acids. Finally, the transcriptomic and metabolomics data were integrated. FASN and SCD in AMPK signaling pathway were directly linked to certain metabolites, including linoleic acid, palmitic acid, and oleic acid. These results indicate that XGHP can inhibit pAMPK expression and negatively regulate FASN and SCD expression during treatment of COPD in order to enhance the biosynthesis of unsaturated fatty acids and maintain energy homeostasis.
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Medicamentos de Ervas Chinesas , Doença Pulmonar Obstrutiva Crônica , Ratos , Humanos , Animais , Transcriptoma , Proteínas Quinases Ativadas por AMP/metabolismo , Cromatografia Líquida , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , Pulmão/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Metabolômica/métodos , Medicamentos de Ervas Chinesas/metabolismoRESUMO
The cell wall polysaccharides were extracted from Sparassis latifolia fruit bodies by acid-alkali and superfine-grinding assisted methods, and the chemical characterization and in vitro immunity activities of these polysaccharide fractions were studied and compared. Results showed that superfine-grinding assisted extraction exhibited the highest yield of polysaccharides (SP, 20.80%) and low ß-glucan content (19.35%) compared with alkaline extracts. The results revealed that the 20% ethanol precipitated fraction (20E) from SP was mainly composed of ß-(1â3)-glucan and α-(1â4)-glucan. With the increase of ethanol precipitation, the fractions (30E, 40E, 50E) were identified as α-(1â4)-glucan with different molecular weights and conformations. Cell wall polysaccharides extracted through NaOH (NSP) and KOH (KSP) extraction had similar yields with 8.90% and 8.83%, respectively. Structural analysis indicated that the purified fraction from KSP (KSP-30E) was a ß-(1â3)-glucan backbone branched with ß-(1â6)-Glcp, while the purified fraction from NSP (NSP-30E) mainly contained ß-(1â3)-glucan with a small number of α-linked-Glcp. The two fractions both exhibited rigid chain conformation in aqueous solutions. All polysaccharide fractions exerted the activity of activating Dectin-1 receptor in vitro, and the KSP-30E mainly identified as ß-(1â3)-glucan with the terminal group via 1â6-linkage attached at every third residue exhibited a stronger enhancing effect than other fractions. Results suggested that KOH extraction could be efficient for the preparation of bioactive ß-(1â3, 1â6)-glucan as a food ingredient.
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In this study, two acidic Biluochun Tea polysaccharides (BTP-A11 and BTP-A12) were investigated comparatively, which mainly consisted of Rha, Ara, Gal and GalA, possibly suggesting their pectic nature. Structurally, their galacturonan backbones composed of â4)-α-D-GalpA-(1â and â2)-α-L-Rhap-(1â were revealed similar, while Ara- and Gal-based branches attached to the O-2 of â2)-α-L-Rhap-(1â were in distinctive types, proportions, extensibilities and branching degrees. This could lead to their different macromolecular characteristics, where BTP-A11 with higher Mw presented a more hyper-branched chain conformation and relatively higher structural flexibility/compactness, thereby resulting in a lower exclusion effect and an insufficient hydrodynamic volume. Besides, better radical scavenging activities in vitro were also determined for Gal-enriched BTP-A11, where a larger surface area containing more H-donating groups were related to its higher Mw, more hyper-branched conformation, lower DM and higher DA. Therefore, the understanding of structure-property-activity relationships was improved to some degrees for acidic Biluochun Tea polysaccharides, which could be potentially required for more applications in food, medical and cosmetic fields.
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Polissacarídeos/química , Polissacarídeos/farmacologia , Chá/química , Fracionamento Químico , Fenômenos Químicos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Substâncias Macromoleculares/química , Substâncias Macromoleculares/isolamento & purificação , Substâncias Macromoleculares/farmacologia , Metilação , Estrutura Molecular , Polissacarídeos/isolamento & purificação , Análise Espectral , Relação Estrutura-AtividadeRESUMO
The role of molecular aggregation was investigated on physicochemical and macromolecular properties of tamarind kernel polysaccharides via partial degalactosylation (TKPs vs. CTKPs). From the results, their main structural characteristics remained when partially degalactosylated, while primary aggregates as fundamental solution behavior were dynamically converted into higher aggregated forms. Micromorphologically, their conformational changes in different forms of crimping and aggregation could be further promoted by partial Gal removal to assemble on larger scales via hydrophobic interactions. Obviously, the aggregation role was unignorable, especially after partial degalactosylation, which affected TKPs and CTKPs differently concerning viscous behaviors, macromolecular characteristics, amorphous-crystalline transition and thermal stability, probably related to distinctiveness in polymerization degree, chemical structure, conformational entropy, solvent-solute interactions, specific intermolecular associations, etc. Therefore, molecular aggregation in tamarind kernel polysaccharides via specific Gal tailoring could be potential in applicable fields, such as postsurgical adhesion, packaging material design and plasma lipid metabolism.
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The molecular aggregation of a galactomannan (NSAP-25) from Sophora alopecuroides L. seeds was investigated, where three polydisperse systems were confirmed during particle size analysis, indicating existence of different aggregates composed of random coil chains revealed by circular dichroism. Morphologically, NSAP-25 aggregate of various sizes (200-1200 nm) was possibly multi-stranded and formed by ellipsoid-like particles (20-60 nm) composed of compact coil chain, exhibiting extended amorphous structure with chain-like branches intertwined. Hence, NSAP-25 aggregation was inevitable, which exerted an unignorable effect on augmenting flexibility (ß↓, γ↓, α↓ and Lp/ML↓) and compactness (ρ↓, df↑ and C∞↓) of branched random coil chain based on macromolecular analysis, especially when concentration increased. Moreover, it could be relevant to thermokinetic behavior of random nucleation and subsequent growth (A2 model and negative ΔS*) as well as good thermal stability (IPDT, ITS, t0.05, Tm and Tp), thus conferring potential applications for NSAP-25 in food and pharmaceutical industries.
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Mananas/química , Sementes/química , Sophora/química , Configuração de Carboidratos , Dicroísmo Circular/métodos , Galactose/análogos & derivados , Cinética , Substâncias Macromoleculares , Microscopia Eletrônica de Transmissão/métodos , Tamanho da Partícula , Temperatura , Termogravimetria/métodosRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by high morbidity, disability, and mortality, which seriously threatens human life and health. Xixin and Ganjiang are classic herb pairs of Zhongjing Zhang, which are often used to treat COPD in China. However, the substance basis and mechanism of action of Xixin-Ganjiang herb pair (XGHP) in the treatment of COPD remain unclear. METHODS: On the website of TCMSP and the DrugBank, effective compounds and targets of XGHP were found. COPD targets were obtained from GeneCards, DisGeNET, and GEO gene chips. Intersecting these databases resulted in a library of drug targets for COPD. Then, intersection targets were used for protein-protein interaction (PPI) and pathway enrichment analysis. Finally, the binding activity between compounds and core genes was evaluated by molecular docking to verify the expression level of PTGS2 and PPARG in rats. RESULTS: Twelve effective compounds and 104 core genes were found in the intersection library, and kaempferol, sesamin, ß-sitosterol, PTGS2, and PPARG were particularly prominent in the network analysis. A total of 113 pathways were obtained and enrichment of the TNF signaling pathway, IL-17 signaling pathway, and C-type lectin receptor signaling pathway was particularly obvious. Molecular docking indicated that kaempferol, sesamin, and ß-sitosterol were closely related to PTGS2 and PPARG and were superior to aminophylline. Key compounds in XGHP could restrict the expression of PTGS2 in the lung tissues of COPD rats and promote the expression of PPARG. CONCLUSION: Inhibition of the expression of inflammatory factor PTGS2 and promotion of the expression of PPARG may be an effective target of XGHP in the treatment of COPD.
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Purposes: To establish a relation between pendular low amplitude high frequency (PLAHF) components and congenital retinal disorders.Methods: Patients who showed PLAHF components in their eye-movement recording between January 2016 to January 2019 were included. Best corrected visual acuity (BCVA), refraction, strabismus assessment, fundus photograph, spectral domain-optical coherence tomography (SD-OCT), full-field electroretinography (f-ERG), clinical ophthalmological examination, and gene tests were used to determine their clinical conditions, especially their retina conditions in all patients.Results: Among 136 patients there were 76 males and 60 females with mean age of 11.4.5 ± 4.5 years. Pure PLAHF waveforms were found in 38 patients (28%), the amplitude of the PLAHF was 2°±1.6° and frequency was 5-10 Hz. Superimposed PLAHF waveforms were found in 98 patients (72%). BCVA was worse than Log MAR1.0 in 94 patients (69%), between LogMar 0.5-1.0 (20/63-20/200) in 30 cases (22%); higher than LogMar 0.5 (20/63) in 12 cases (9%). Fifty-eight patients were diagnosed with exotropia and six patients with esotropia. Abnormal Fundus were found in 71 cases (52%), fovea hypoplasia was identified with OCT in 95 cases (70%) and retinal thinning in 92 cases (68%). Abnormal on-off VEP were found in 116 cases (85%). The f-ERG responses were reduced in all patients. In 46 patients, gene mutations were found to related to retinal disease, including 3 congenital stationary night blindness (CSNB), 14 achromatopsia (ACHM), 5 Aland Island eye disease (AIED), 7 Alstrom syndrome (AS), 11 Leber congenital amaurosis (LCA), 6 cone-rod dystrophy (CRD).Conclusions: Patients presenting with PLAHF usually had retinal disorders.
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Nistagmo Patológico/diagnóstico , Distrofias Retinianas/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Eletronistagmografia , Eletrorretinografia , Feminino , Humanos , Lactente , Masculino , Nistagmo Patológico/fisiopatologia , Distrofias Retinianas/fisiopatologia , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Adulto JovemRESUMO
A polysaccharide (PFPP) from purple passion fruit peel was optimally extracted, with the highest yield (10.05%, w/w) obtained under 35⯰C extraction temperature, 240â¯W ultrasonic power, 65:1â¯mL/g liquid-to-solid ratio, 0.6% (w/v) ammonium oxalate, 30â¯min extraction time and pH 2.0. According to composition analyses, pectic PFPP and its fractions (PFPP-10, -15 and -20) were revealed as linear homogalacturonans interrupted by rhamnogalacturonan I in different lengths and extensities, where low esterification degrees (35.35-39.66%) were indicated via FT-IR. Furthermore, based on macromolecular models, comprehensive analyses on macromolecular and conformational characterizations of PFPP fractions were conducted quantitatively through, e.g., shape factor (1.42-1.79), Mark-Houwink-Sakurada exponent (0.55-0.74), conformational power-law exponent (0.52-0.58), fractal dimension (1.72-1.94) and persistence length (6.73-13.47â¯nm). Therefore, different semi-flexible coil conformations were proposed schematically, where lower molecular-weight PFPP fractions were less flexible. This could provide a molecular basis for precise re-utilizations of PFPP in food and pharmaceutical industries.
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In this study, an ultrasonic-extracted polysaccharide (nCPTP-55) was obtained with the highest yield (61.08%, w/w) from tamarind pulp, which consisted chiefly of total sugar (85.98%, w/w) with few protein (2.10%, w/w). Monosaccharide analysis showed nCPTP-55 was mainly composed of arabinose (39.19 mol%) and glucose (50.48 mol%) with negligible GlcA (2.05 mol%), indicating the neutral nature of nCPTP-55, which was further elucidated structurally via GC-MS and NMR, i.e., an arabinoglucan composed of â3)-ß-D-Glcp-(1â backbone with only T-α-L-Araf-(1â branched at O-4 (27.82%) and O-6 (39.99%), resulting in relatively high A/G ratio (0.68-0.70). Based on MM2 minimized energy, the 3D schematic structures of nCPTP-55 could be considered as structural basis for its conformational behavior, which was preliminarily estimated via HPSEC-MALLS as between compact sphere and loosely hyper-branched chain (ρ = 0.84). Therefore, the relationship between molecular structure and conformational behavior was basically established for nCPTP-55, which was in a bid to have a better knowledge of its structure-property and structure-bioactivity relationships potentially required for more applications in food, cosmetic and pharmaceutical fields.
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Mucoproteínas/química , Polissacarídeos/química , Relação Estrutura-Atividade , Tamarindus/química , Arabinose/química , Estrutura Molecular , Monossacarídeos/química , Mucoproteínas/isolamento & purificação , Mucoproteínas/ultraestrutura , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/ultraestrutura , Polissacarídeos/isolamento & purificação , Polissacarídeos/ultraestrutura , Açúcares/química , Tamarindus/efeitos da radiação , UltrassomRESUMO
OBJECTIVE: The aim of this study was to investigate the changes in early and late washout rates of 99mTc-methoxyisobutylisonitrile (MIBI) in hypertrophic cardiomyopathy (HCM), and to analyze the relationships between early and late washout rates and the hypertrophic thickness of left ventricular (LV) wall. METHODS: The patients who were clinically diagnosed as positive for HCM underwent 99mTc-MIBI static planar and gated single-photon emission computed tomography (SPECT) imaging. Early (90 min after the intravenous injection) and late (4 h after the intravenous injection) washout rates of 99mTc-MIBI between HCM group and normal control group were compared. Linear correlation analysis was made between early and late washout rates and the hypertrophic thickness of LV wall measured by gated SPECT. RESULTS: The early and late washout rates of 99mTc-MIBI in normal control group were (18.90+/-3.70) and (31.27+/-4.04)%, respectively; and the washout rates in HCM group were (27.77+/-2.60) and (42.66+/-3.30)%, respectively. Significant statistical differences were observed in the early and late washout rates of 99mTc-MIBI between HCM group and normal control group (t=-7.320 and t=-8.069, both P<0.01). Correlations between early and late washout rates and the maximal hypertrophic thickness of LV wall obtained by gated SPECT were excellent (r=0.611, P<0.05; r=0.873, P<0.01, respectively). CONCLUSION: The early and late washout rates of 99mTc-MIBI in HCM group were significantly higher than those in normal control group, and both the early and late washout rates correlated well with the hypertrophic thickness of LV wall.
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Cardiomiopatia Hipertrófica/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Sestamibi , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Tecnécio Tc 99m Sestamibi/farmacocinética , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Biomass gasification stations are facing many hazard factors, therefore, it is necessary to make hazard assessment for them. In this study, a novel hazard assessment method called extended set pair analysis (ESPA) is proposed based on set pair analysis (SPA). However, the calculation of the connection degree (CD) requires the classification of hazard grades and their corresponding thresholds using SPA for the hazard assessment. In regard to the hazard assessment using ESPA, a novel calculation algorithm of the CD is worked out when hazard grades and their corresponding thresholds are unknown. Then the CD can be converted into Euclidean distance (ED) by a simple and concise calculation, and the hazard of each sample will be ranked based on the value of ED. In this paper, six biomass gasification stations are introduced to make hazard assessment using ESPA and general set pair analysis (GSPA), respectively. By the comparison of hazard assessment results obtained from ESPA and GSPA, the availability and validity of ESPA can be proved in the hazard assessment for biomass gasification stations. Meanwhile, the reasonability of ESPA is also justified by the sensitivity analysis of hazard assessment results obtained by ESPA and GSPA.