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The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.
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Objective To study the effect of morphological characteristics of modular inner branched stent graft (MIBSG) on hemodynamic performance of postoperative aortic arch based on parameterized MIBSG model. Methods The fluid-structure interaction model of blood-MIBSG coupling performance was solved, and the effects of stent branch angles, stent diameters on hemodynamic characteristics were analyzed. Results With the increase of angles between branch stent and aortic arch stent, blood flow within the branch decreased, but the stress and displacement increased. With the decrease of stent diameters, blood flow perfusion decreased significantly, but the stress and displacement increased first, and then decreased. Conclusions The morphological changes of MIBSG not only have an impact on blood perfusion rate of branch stent, but also affect the stress exerted on stent and the corresponding displacement. Before application in clinic treatment of aortic arch diseases, the movement and torsion of MIBSG should been taken into full account in operation plan according to the actual situation.
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The effect of parasitic ions on the results of ultraviolet A (UVA) cross-linking in iontophoresis was still not clear. In this work, the porcine sclera was cross-linked by riboflavin lactate Ringer's solution (group A) and riboflavin normal saline (group B)
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Animales , Colágeno , Reactivos de Enlaces Cruzados , Iones , Iontoforesis , Permeabilidad , Fármacos Fotosensibilizantes/farmacología , Riboflavina , Esclerótica , Porcinos , Rayos UltravioletaRESUMEN
Objective:To propose the application of recognizing bone species by touching blindly (ARBTB) and verify its application effect in human anatomy experimental courses.Methods:The study included experiment 1 and experiment 2, and the research objects were 60 students majoring in clinical medicine in Batch 2019 and 60 students majoring in preventive medicine in Batch 2018, respectively. The research objects in each experiment were randomized into mainstream teaching method group and ARBTB group, with 30 students in each group. In experiment 1, after students studying for the same hours, both of two groups carried out the same test, and then the average scores of the two groups were compared. In experiment 2, the average time spent by the two groups of students in osteology learning was compared.Results:In experiment 1, ARBTB group's average score of the test was significantly higher than that of the mainstream teaching group ( P<0.001). In experiment 2, the ARBTB group took much less time in osteology learning than the mainstream teaching group ( P<0.001). Conclusion:Compared with the mainstream teaching method, ARBTB is more effective in osteology learning, which is worth popularizing.
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Objective To investigate the differences in mechanical properties of the sclera in different regions. Methods The sclera of sus scrofa was divided into 3 regions, namely, anterior, equatorial and posterior area. Local indentation was performed on different areas of the whole sclera. Strip specimens of different regions were circumcised along the equatorial direction, and subjected to uniaxial stretching by INSTRON 5544. Results Within the normal physiological stress range, the stiffness at anterior, equatorial, and posterior area of the sclera measured by local indentation was (0.91±0.21), (0.6±0.16), (0.39±0.13) MPa, respectively. The elastic modulus at anterior, equatorial, and posterior area of the sclera measured by uniaxial stretching was (1-28±0.37), (0.95±0.31), (0.72±0.28) MPa, respectively. Conclusions The local indentation could reflect regional mechanical properties of the sclera. The anterior sclera performed a higher stiffness than the equatorial and posterior areas. The results provide references for further study on the pathogenesis of ocular diseases including myopia.
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Objective To study the changes of transcriptome levels in a Bama minipig model of hypertrophic scar during wound healing and pressure therapy by using RNA sequencing (RNA-seq) technique. Methods The Bama minipig model was established by skin wounds from the back and pressure (3.4 kPa) was initiated at 60 days after skin injury. Total RNA was extracted from scar tissues at 0, 14, 30, 60, and 90 days after skin injury and then sequenced. The resulting sequences were mapped to porcine reference genomes and transcriptomes were reconstructed to search for differentially expressed genes (DEGs). The DEGs were further subjected to GO and KEGG analysis using bioinformatics method, while part of the genes were selected for verification using qRT-PCR. Results After preprocessing, more than 78% reads in each group were accurately aligned to the reference sequence. The DEGs identification result showed that 568 genes were differentially expressed after pressure treatment, with 289 up-regulated and 279 down-regulated. GO enrichment analysis revealed that DEGs in each group were mainly associated with extracellular matrix, tissue development and skin development. KEGG analysis showed that the DEGs in each group during wound healing were mainly enriched in extracellular matrix-receptor interactions, focal adhesion and apoptosis pathways; while the DEGs after pressure treatment were mainly enriched in PI3K-Akt and MAPK signaling pathway except the pathways mentioned. qRT-PCR showed that the expression patterns of 6 DEGs were consistent with RNA-seq analysis, confirming the reliability of RNA-seq result. Conclusions RNA-Seq analysis identified differentially expressed genes in animal model of scars during wound healing and pressure therapy, which provided experimental evidence for clinical scar treatment.
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Objective To study the changes of transcriptome levels in a Bama minipig model of hypertrophic scar during wound healing and pressure therapy by using RNA sequencing (RNA-seq) technique. Methods The Bama minipig model was established by skin wounds from the back and pressure (3.4 kPa) was initiated at 60 days after skin injury. Total RNA was extracted from scar tissues at 0, 14, 30, 60, and 90 days after skin injury and then sequenced. The resulting sequences were mapped to porcine reference genomes and transcriptomes were reconstructed to search for differentially expressed genes (DEGs). The DEGs were further subjected to GO and KEGG analysis using bioinformatics method, while part of the genes were selected for verification using qRT-PCR. Results After preprocessing, more than 78% reads in each group were accurately aligned to the reference sequence. The DEGs identification result showed that 568 genes were differentially expressed after pressure treatment, with 289 up-regulated and 279 down-regulated. GO enrichment analysis revealed that DEGs in each group were mainly associated with extracellular matrix, tissue development and skin development. KEGG analysis showed that the DEGs in each group during wound healing were mainly enriched in extracellular matrix-receptor interactions, focal adhesion and apoptosis pathways; while the DEGs after pressure treatment were mainly enriched in PI3K-Akt and MAPK signaling pathway except the pathways mentioned. qRT-PCR showed that the expression patterns of 6 DEGs were consistent with RNA-seq analysis, confirming the reliability of RNA-seq result. Conclusions RNA-Seq analysis identified differentially expressed genes in animal model of scars during wound healing and pressure therapy, which provided experimental evidence for clinical scar treatment.
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The mechanical properties of the aorta tissue is not only important for maintaining the cardiovascular health, but also is closely related to the development of cardiovascular diseases. There are obvious differences between the ventral and dorsal tissues of the descending aorta. However, the cause of the difference is still unclear. In this study, a biaxial tensile approach was used to determine the parameters of porcine descending aorta by analyzing the stress-strain curves. The strain energy functions Gasser-Ogden-Holzapfel was adopted to characterize the orthotropic parameters of mechanical properties. Elastic Van Gieson (EVG) and Sirius red stain were used to observe the microarchitecture of elastic and collagen fibers, respectively. Our results showed that the tissue of descending aorta had more orthotropic and higher elastic modulus in the dorsal region compared to the ventral region in the circumferential direction. No significant difference was found in hyperelastic constitutive parameters between the dorsal and ventral regions, but the angle of collagen fiber was smaller than 0.785 rad (45°) in both dorsal and ventral regions. The arrangement of fiber was inclined to be circumferential. EVG and Sirius red stain showed that in outer-middle membrane of the descending aorta, the density of elastic fibrous layer of the ventral region was higher than that of the dorsal region; the amount of collagen fibers in dorsal region was more than that of the ventral region. The results suggested that the difference of mechanical properties between the dorsal and ventral tissues in the descending aorta was related to the microstructure of the outer membrane of the aorta. In the relatively small strain range, the difference in mechanical properties between the ventral and dorsal tissues of the descending aorta can be ignored; when the strain is higher, it needs to be treated differently. The results of this study provide data for the etiology of arterial disease (such as arterial dissection) and the design of artificial blood vessel.
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Animales , Aorta Torácica , Fisiología , Fenómenos Biomecánicos , Colágeno , Módulo de Elasticidad , Estrés Mecánico , PorcinosRESUMEN
Objective@#To study the characteristics of lung adenocarcinoma driver gene variants detected by next generation sequencing (NGS) and quantitative fluorescence PCR.@*Methods@#NGS was performed on 372 surgical resections from primary lung adenocarcinoma patients to detect 10 driver gene mutations, single-nucleotide variants(SNV), insertion/deletion and gene fusions; and quantitative fluorescence PCR were performed on 169 surgical resections from primary lung adenocarcinoma patients to detect nine driver gene hotspot mutations. Variants of VAF (variant allele frequency)≥1.0% were classified into 1 of 4 levels according to the guidelines and the precision oncology knowledge base of OncoKB, and the characteristics were investigated.@*Results@#Sixty seven variants(leve1-4) were found by NGS, the positive rate of total mutations was 86.6% (322/372), in which variants at four levels were detected: levelⅠvariant, which was recognized as biomarker predictive of response to an FDA/NMPA approved drug in non-small cell lung cancer (NSCLC), was 71.2% (265/372);level Ⅱ variant, which was recognized as being standard care by the NCCN or other expert panels, was 3.0% (11/372); levelⅢA, a variant with compelling clinical evidence supports the biomarker as being predictive of response to a drug in this indication 3.0% (11/372); levelⅢB, a variant with compelling clinical evidence supports the biomarker as being predictive of response to a drug in another indication, was 4.3% (16/372); and level Ⅳ, a variant with compelling biological evidence supports the biomarker as being predictive of response to a drug, was 8.1% (30/372). The positive rate of unknown clinical significance and/or benign/likely benign variants was 18.8% (70/372). The positive rate of mutations detected by quantitative fluorescence PCR was 81.7% (138/169). Eighteen of the 20 samples showed concordance between NGS and quantitative fluorescence PCR. The two discordant cases could be due to the lack of coverage of two mutation sites in fluorescence PCR: EGFR c. 2571_2573delinsTCG(p. L858R), and HIP1-ALK_H19:A20 fusion.@*Conclusions@#Lung adenocarcinoma driver gene variants occur mainly in hotspot region, and NGS can comprehensively detect the driver gene variants of significant and potential clinical significance. NGS should be recommended when multiple genes need to be tested.
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Gynaecomastia is a kind of benign and hyperplastic disease of male breast tissue. Based on the literature at home and abroad, different classification or standard of gynaecomastia has been expounded respectively from the pathogenesis, age, pathology, degree and iconography, and several common classification has been compared. Summarizing the advantages and disadvantages of these classification standards, evidence can be provided for clinical diagnosis and preoperative assessment of gynaecomastia, improvement direction can be offered for domestic classification criteria.
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Objective To study the mechanical properties of porcine descending aorta. Methods The porcine descending aortas were divided into 5 groups by the distance from the heart, and tissues in each group were subdivided into ventral-quadrant part and lateral-quadrant part. Stress-stretch curves were obtained by using uniaxial tension test. The moduli of elastic and collagen fiber and collagen fiber recruitment parameter of tissues in 5 groups (Position 1-5) were first analyzed by a classical mathematical model. Then the mechanical differences between tissues of ventral quadrant and lateral quadrant were compared. Results The modulus of circumferential collagen fibers increased gradually away from the heart. The modulus of circumferential elastic fibers had the same trend except for tissues at Position 5 (the most distal one). The elastic fibers modulus of tissues decreased at Position 5. At the most distal position, the circumferential and axial elastic fiber modulus of the lateral quadrant was lower than that of ventral quadrant by 19% and 33%, respectively. The axial and the elastic fiber modulus of the ventral quadrant was similar with that of tissues at Position 4 and 5. For the whole descending aorta, the circumferential collagen fiber modulus of the lateral quadrant was higher than that of ventral quadrant by 26% and the circumferential elastic fiber modulus of the lateral quadrant was higher than that of ventral quadrant by 16% at the proximal 4 positions. Conclusions The circumferential mechanical properties of porcine descending aorta were related with regions. The ventral quadrant of the most distal aorta showed abnormally soft trend. The research findings can be used to better understand the mechanism of aorta and improve the spatial accuracy of computer models.
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Objective To contrastively analyze the performance of two kinds of blood cell separators for apheresis platelets . Methods 80 blood donors were selected from 4 234 healthy apheresis platelet donors and their data before and after apheresis platelets were respectively collected by using two kinds of different blood cell separators Trima and Amicus .The product quality during the collection process ,residual WBC and RBC count ,acquisition time ,collection efficiency ,scrapping situation and safety were performed the comparative analysis between the two kinds of blood cell separator .Results In the case of the difference of the basic parameters before apheresis platelet having no statistical significance ,the two kinds of blood cell separator had no differences in the aspects of product quality ,processing blood amount and the use amount of anticoagulants(P>0 .05);but there were statisti‐cal differences in the aspects of acquisition time ,collection efficiency and pipeline residual blood amount (P<0 .05) .Conclusion Two kinds of blood cell separators have their own advantages and disadvantages during the use process ,so the blood cell separator should be selected according to the physical quality and their own characteristics of blood donors .