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Ag-Sn-In-Ni-Te alloy ingots were produced through a heating-cooling combined mold continuous casting technique; they were then drawn into wires. However, during the drawing process, the alloy wires tended to harden, making further diameter reduction challenging. To overcome this, heat treatment was necessary to soften the previously drawn wires. The study investigated how variations in heat treatment temperature and holding time affected the microstructure, microhardness and corrosion resistance of the alloy wires. The results indicate that the alloy wires subjected to heat treatment at 700 °C for 2 h not only exhibited a uniform microstructure distribution, but also demonstrated low microhardness and excellent corrosion resistance.
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Single-cell proteomic analyses are of fundamental importance in order to capture biological heterogeneity within complex cell systems' heterogeneous populations. Mass spectrometry (MS)-based proteomics is a promising alternative for quantitative single-cell proteomics. Various techniques are continually evolving to address the challenges of limited sample material, detection sensitivity, and throughput constraints. In this chapter, we describe a nanoliter-scale glass-oil-air-droplet (gOAD) chip engineered for heat tolerance, which combines droplet-based microfluidics and shotgun proteomic analysis techniques to enable multistep sample pretreatment.
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Verre , Protéomique , Analyse sur cellule unique , Protéomique/méthodes , Analyse sur cellule unique/méthodes , Analyse sur cellule unique/instrumentation , Verre/composition chimique , Humains , Huiles/composition chimique , Spectrométrie de masse/méthodes , Techniques d'analyse microfluidique/instrumentation , Techniques d'analyse microfluidique/méthodes , Laboratoires sur puces , Air , Protéome/analyse , Nanotechnologie/méthodes , Nanotechnologie/instrumentation , Microfluidique/méthodes , Microfluidique/instrumentationRÉSUMÉ
This study aims to optimize the conditions for the formation of neutrophil extracellular traps(NETs) in vitro, so as to establish a relatively stable experimental research platform. Different conditions were compared, including commonly used laboratory animals(rats and mice) and a variety of cell sources(bone marrow neutrophils and peripheral blood neutrophils separated by percoll density gradient centrifugation). Different inducers like lipopolysaccharide(LPS) and phorbol 12-myristate 13-acetate(PMA) were used for induction in vitro. Myeloperoxidase(MPO)/citrullinated histone H3(CitH3)/DAPI immunofluorescence and cell free DNA(cf-DNA) content determination were used for comprehensive evaluation to screen the optimal conditions for the formation of NETs induced in vitro. Furthermore, the stability of the selected conditions for inducing the formation of NETs in vitro was evaluated by tetramethylpyrazine(TMP), an active component in Chinese herbal medicines. The results showed that coated poly-D-lysine(PDL) induced the formation of NETs in bone marrow neutrophils of mice to a certain extent. Both LPS and PMA significantly up-regulated the protein levels of MPO and CitH3 in mouse bone marrow neutrophils and elevated the cfDNA level in the supernatant of rat peripheral blood neutrophils. The cfDNA level in the PMA-induced group increased more significantly than that in the LPS-induced group(P<0.05). The results of immunofluorescence staining showed that the expression of MPO and CitH3 in mouse bone marrow neutrophils, rat bone marrow neutrophils, and rat peripheral blood neutrophils were significantly increased after PMA induction, especially in rat peripheral blood neutrophils. TMP significantly down-regulated the protein levels of MPO, CitH3, and neutrophil elastase(NE) in rat peripheral blood neutrophils induced by PMA. In conclusion, treating the peripheral blood neutrophils of rats with PMA is the optimal condition for inducing the formation of NETs in vitro. This study provides an optimal platform for in vitro studies based on NETs and a basis for studying the effects of traditional Chinese medicines targeting NETs.
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Pièges extracellulaires , Granulocytes neutrophiles , Myeloperoxidase , Pièges extracellulaires/effets des médicaments et des substances chimiques , Pièges extracellulaires/métabolisme , Animaux , Granulocytes neutrophiles/effets des médicaments et des substances chimiques , Granulocytes neutrophiles/cytologie , Souris , Rats , Myeloperoxidase/métabolisme , Myeloperoxidase/génétique , 12-Myristate-13-acétate de phorbol/pharmacologie , Mâle , Lipopolysaccharides/pharmacologie , Rat Sprague-Dawley , Histone/métabolisme , Histone/génétique , HumainsRÉSUMÉ
The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL.
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Marqueurs biologiques tumoraux , ADN tumoral circulant , Lymphome B diffus à grandes cellules , Mutation , Humains , Lymphome B diffus à grandes cellules/liquide cérébrospinal , Lymphome B diffus à grandes cellules/génétique , Lymphome B diffus à grandes cellules/diagnostic , Femelle , Mâle , Adulte d'âge moyen , Marqueurs biologiques tumoraux/liquide cérébrospinal , Marqueurs biologiques tumoraux/génétique , Sujet âgé , Adulte , ADN tumoral circulant/liquide cérébrospinal , ADN tumoral circulant/génétique , ADN tumoral circulant/sang , Pronostic , Sujet âgé de 80 ans ou plus , Jeune adulte , Études prospectivesRÉSUMÉ
A series of Ti41Zr25Be34-xNix (x = 4, 6, 8, 10 at.%) and Ti41Zr25Be34-xCux (x = 4, 6, 8 at.%) bulk metallic glasses were investigated to examine the influence of Ni and Cu content on the viscosity, thermoplastic formability, and nanoindentation of Ti-based bulk metallic glasses. The results demonstrate that Ti41Zr25Be30Ni4 and Ti41Zr25Be26Cu8 amorphous alloys have superior thermoplastic formability among the Ti41Zr25Be34-xNix and Ti41Zr25Be34-xCux amorphous alloys due to their low viscosity in the supercooled liquid region and wider supercooled liquid region. The hardness and modulus exhibit obvious variations with increasing Ni and Cu content in Ti-based bulk metallic glasses, which can be attributed to alterations in atomic density. Optimal amounts of Ni and Cu in Ti-based bulk metallic glasses enhance thermoplastic formability and mechanical properties. The influence of Ni and Cu content on the hardness of Ti-based bulk metallic glasses is discussed from the perspective of the mean atomic distance.
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Design the electrocatalysts without noble metal is still a challenge for oxygen evolution reaction (OER) in acid media. Herein, we reported the manganese (Mn) doping method to decrease the concentration of oxygen vacancy (VO) and form the Mn-O structure adjacent octahedral sites in spinel NiCo2O4-δ (NiMn1.5Co3O4-δ), which highly enhanced the activity and stability of spinel NiCo2O4-δ with a low overpotential (η) of 280â mV at j=10â mA cm-2 and long-term stability of 80â h in acid media. The isotopic labelling experiment based on differential electrochemical mass spectrometry (DEMS) clearly demonstrated the lattice oxygen in NiMn1.5Co3O4-δ is more stable due to strong Mn-O bond and shows synergetic adsorbate evolution mechanism (SAEM) for acid OER. Density functional theory (DFT) calculations reveal highly increased oxygen vacancy formation energy (EVO) of NiCo2O4-δ after Mn doping. More importantly, the highly hydrogen bonding between Mn-O and *OOH adsorbed on adjacent Co octahedral sites promote the formation of *OO from *OOH due to the greatly enhanced charge density of O in Mn substituted sites.
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A large proportion of patients with chronic pain experience co-morbid anxiety. The medial prefrontal cortex (mPFC) is proposed to underlie this comorbidity, but the molecular and neuronal mechanisms are not fully understood. Here, we reported that impaired neuronal macroautophagy in the prelimbic cortical (PrL) subregion of the mPFC paralleled the occurrence of anxiety-like behaviors in rats with chronic spared nerve injury (SNI). Intriguingly, such macroautophagy impairment was mainly observed in a FOS/c-Fos+ neuronal subpopulation in the PrL. Chemogenetic inactivation of this comorbid anxiety-related neuronal ensemble relieved pain-induced anxiety-like behaviors. Rescuing macroautophagy impairment in this neuronal ensemble relieved chronic pain-associated anxiety and mechanical allodynia and restored synaptic homeostasis at the molecular level. By contrast, artificial disruption of macroautophagy induced early-onset co-morbid anxiety in neuropathic rats, but not general anxiety in normal rats. Taken together, our work identifies causal linkage between PrL neuronal macroautophagy dysfunction and comorbid anxiety in neuropathic pain and provides novel insights into the role of PrL by differentiating its contribution in pain-induced comorbid anxiety from its modulation over general anxiety-like behaviors.Abbreviation: AAV: adeno-associated viruses; ACC: anterior cingulate cortex; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG12: autophagy related 12; CAMK2/CaMKII: calcium/calmodulin-dependent protein kinase II; CNO: clozapine-N-oxide; CQ: chloroquine; DIA: data independent acquisition; DIO: double floxed inverse orf; DLG4/PSD-95: discs large MAGUK scaffold protein 4; Dox: doxycycline; GABA: γ-aminobutyric acid; GFP: green fluorescent protein; GO: gene ontology; Gi: inhibitory guanine nucleotide-binding proteins; HsCHRM4/M4D: human cholinergic receptor muscarinic 4; HsSYN: human synapsin; KEGG: Kyoto encyclopedia of genes and genomes; LAMP1: lysosomal-associated membrane protein 1; LC3-II: PE conjugated microtubule-associated protein 1 light chain3; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; mPFC: medial prefrontal cortex; P2A: 2A self-cleaving peptide; PPI: protein-protein interaction networks; PrL: prelimbic cortex; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; rtTA: reverse tetracycline-transactivator; SDS-PAGE: sodium dodecylsulfate-polyacrylamide gel electrophoresis; SHANK3: SH3 and multiple ankyrin repeat domains 3; SLC1A1/EAAC1: solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, systemXag), member 1; SNAP23: synaptosomal-associated protein 23; SNI:spared nerve injury; SQSTM1/p62: sequestosome 1; SYT3: synaptotagmin 3; TRE: tetracycline-responsive element; TRE3G: third-generation tetracycline-responsive element.
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Anxiété , Macroautophagie , Névralgie , Neurones , Cortex préfrontal , Animaux , Névralgie/métabolisme , Cortex préfrontal/métabolisme , Rats , Neurones/métabolisme , Mâle , Macroautophagie/physiologie , Rat Sprague-Dawley , Comportement animal , Douleur chronique/métabolisme , Autophagie/physiologie , Calcium-Calmodulin-Dependent Protein Kinase Type 2/métabolisme , HyperalgésieRÉSUMÉ
Objective: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with a high incidence of complications in the mid and late stages of gestation. This study investigates differences in the composition of intestinal flora among pregnant women diagnosed with ICP, employing Illumina MiSeq high-throughput sequencing technology. Methods: This case-control study obtained patient data from the hospital information system (HIS) and the laboratory information system (LIS). Fecal samples were collected from 25 pregnant women who did not undergo intestinal preparation before delivery between December 2020 and March 2021. Whole-genome analysis was performed. PCR was used to amplify the 16S rRNA V3-V4 variable region, which was then sequenced. Alpha and beta diversity were computed, and the maternal intestinal flora's abundance and composition characteristics were analyzed. Differences in intestinal flora between the two sample groups were examined. Results: Bacteroides and Proteobacteria exhibited positive correlations with TBIL and IBIL. Betaproteobacteria, Gammaproteobacteria, and Erysipeiotrichi showed positive correlations with TBIL, IBIL, and DBIL, while Lactobacillus, Delftia, and Odoribacter demonstrated positive correlations with ALT. Conclusion: The ICP group displayed significantly higher levels of total bile acid and ALT compared to the control group. The intestinal flora composition comprised four primary phyla: Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria. ICP patients exhibited a lower relative abundance of intestinal flora across different levels of community composition when compared to the control group. Specific correlations between certain intestinal flora and clinical liver parameters were identified.
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Reflux esophagitis is an inflammatory disease of esophageal mucosa damage caused by the reflux of gastric contents into the esophagus. Its incidence is on the rise, and it has become an important precancerous disease of esophageal cancer. Studies have shown that the continuous inflammatory response stimulates the esophageal mucosa, causing abnormal proliferation of esophageal epithelial cells and damage to esophageal mucosal tissue, which eventually leads to the occurrence of heterogeneous hyperplasia and even carcinogenesis. The nuclear transcription factor-kappa B (NF-κB) signaling pathway is one of the most classical inflammatory and cancer signaling pathways. It has been found that abnormal activation of the NF-κB signaling pathway is crucial to the development and prognosis of reflux esophagitis and esophageal cancer. It is widely involved in the proliferation, autophagy, apoptosis, and inflammatory response of esophageal epithelial cells and tumor cells, accelerating the transformation of reflux esophagitis to esophageal cancer and making it a potential target for the treatment of reflux esophagitis and esophageal cancer. Currently, there is no specific treatment for reflux esophagitis and esophageal cancer, and large side effects often appear. Therefore, finding a promising and safe drug remains a top priority. In recent years, traditional Chinese medicine scholars have conducted a lot of research on NF-κB signaling pathway, and the results indicate that NF-κB signaling pathway is an important potential target for traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer, but there is a lack of comprehensive and systematic elaboration. Therefore, this paper summarized the relevant studies in recent years, analyzed the relationship among NF-κB signaling pathway, reflux esophagitis, esophageal cancer, and transformation from inflammation to cancer, and reviewed the research literature on the regulation of the NF-κB signaling pathway in traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer, so as to provide new ideas for the prevention and treatment of reflux esophagitis and esophageal cancer.
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Objectiveï¼ To analyze the efficacy of microwave ablation (MWA) guided by computed tomography (CT) and 1.5T magnetic resonance (MR) in the treatment of VX2 para-vascular liver tumor model in rabbits. Materials and Methods Sixty para-vascular VX2 liver tumor models in rabbits were randomly divided into CT-guided microwave ablation group (CT group, n=35) and MR-guided microwave ablation group (MR group, n=35). The complete ablation rate, mean operation time, postoperative complication rate and mean survival time were compared between the two groups. Results In the CT group, the rate of complete ablation was 68.6% (24/35), and the mean operation time was 42.1 ± 9.7 minutes. Three cases had ascites and one case had abdominal wall injury. In the MR group, the rate of complete ablation was 94.2% (33/35), and the mean operation time was 53.4 ± 10.9 minutes. One case was complicated with ascites. No serious complications such as pneumothorax, liver abscess, pleural effusion and diaphragm perforation were found in both groups. Between the two groups, the difference in complete ablation rate was statistically significant (P=0.006 ï¼ 0.05). A statistically significant difference can also be found in mean operation time (P ï¼ 0.01). The follow-up time was 21 days after the operation. As for the postoperative complication rate (11.4% in the CT group and 2.9% in the MR group, P=0.353) and mean survival time (16.9 ± 1.8 days in CT group, 18.3 ± 2.3 days in the MR group, P=0.925), the differences were not statistically significant. Conclusion Compared with CT guidance, although the microwave ablation time under MR guidance was longer, the complete ablation rate under MR guidance was high, which proved that MR guidance was a more effective way of microwave ablation guidance and was worth promoting in the clinic. In this experiment, the postoperative complication rate was lower in the MR group, although the difference was not statistically significant, which may be related to the small sample size, and the subsequent study on the postoperative complication rate can increase the sample content.
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Copper-coated graphite and copper mixture powders were deposited on AZ31B magnesium alloy and 6061 T6 aluminum alloy substrates under different process parameters by a solid-state cold spray technique. The microstructure of the copper-coated graphite and copper composite coatings was visually examined using photographs taken with an optical microscope and a scanning electron microscope. The surface roughness of the coatings was investigated with a 3D profilometer. The thickness of the coatings was determined through the analysis of the microstructure images, while the adhesion of the coatings was characterized using the scratch test method. The results indicate that the surface roughness of the coatings sprayed on the two different substrates gradually decreases as gas temperature and gas pressure increase. Additionally, the thickness and adhesion of the coatings deposited on the two different substrates both increase with an increase in gas temperature and gas pressure. Comparing the surface roughness, thickness, and adhesion of the coatings deposited on the two different substrates, the surface roughness and adhesion of the coatings on the soft substrate are greater than those of the coatings on the hard substrate, while the thickness of the coatings is not obviously affected by the hardness of the substrate. Furthermore, it is noteworthy that the surface roughness, thickness, and adhesion of the copper-coated graphite and copper composite coatings sprayed on the two different substrates exhibit a distinct linear relationship with particle velocity.
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Sperm-induced Ca2+ rise is critical for driving oocyte activation and subsequent embryonic development, but little is known about how lasting Ca2+ oscillations are regulated. Here it is shown that NLRP14, a maternal effect factor, is essential for keeping Ca2+ oscillations and early embryonic development. Few embryos lacking maternal NLRP14 can develop beyond the 2-cell stage. The impaired developmental potential of Nlrp14-deficient oocytes is mainly caused by disrupted cytoplasmic function and calcium homeostasis due to altered mitochondrial distribution, morphology, and activity since the calcium oscillations and development of Nlrp14-deficient oocytes can be rescued by substitution of whole cytoplasm by spindle transfer. Proteomics analysis reveal that cytoplasmic UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is significantly decreased in Nlrp14-deficient oocytes, and Uhrf1-deficient oocytes also show disrupted calcium homeostasis and developmental arrest. Strikingly, it is found that the mitochondrial Na+ /Ca2+ exchanger (NCLX) encoded by Slc8b1 is significantly decreased in the Nlrp14mNull oocyte. Mechanistically, NLRP14 interacts with the NCLX intrinsically disordered regions (IDRs) domain and maintain its stability by regulating the K27-linked ubiquitination. Thus, the study reveals NLRP14 as a crucial player in calcium homeostasis that is important for early embryonic development.
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Calcium , Nucleoside-triphosphatase , Sperme , Humains , Mâle , Calcium/métabolisme , Homéostasie/physiologie , Ovocytes/métabolisme , Sperme/métabolisme , Échangeur sodium-calcium/génétique , Échangeur sodium-calcium/métabolisme , Ubiquitination , Animaux , Souris , Nucleoside-triphosphatase/métabolismeRÉSUMÉ
Dynamic reconstruction of metal sulphides during electrocatalytic oxygen evolution reaction (OER) has hampered the acquisition of legible evidence for comprehensively understanding the phase-transition mechanism and electrocatalytic activity origin. Herein, modelling on a series of cobalt-nickel bimetallic sulphides, we for the first time establish an explicit and comprehensive picture of their dynamic phase evaluation pathway at the pre-catalytic stage before OER process. By utilizing the in-situ electrochemical transmission electron microscopy and electron energy loss spectroscopy, the lattice sulphur atoms of (NiCo)S1.33 particles are revealed to be partially substituted by oxygen from electrolyte to form a lattice oxygen-sulphur coexisting shell surface before the generation of reconstituted active species. Such S-O exchange process is benefitted from the subtle modulation of metal-sulphur coordination form caused by the specific Ni and Co occupation. This unique oxygen-substitution behaviour produces an (NiCo)OxS1.33-x surface to reduce the energy barrier of surface reconstruction for converting sulphides into active oxy/hydroxide derivative, therefore significantly increasing the proportion of lattice oxygen-mediated mechanism compared to the pure sulphide surface. We anticipate this direct observation can provide an explicit picture of catalysts' structural and compositional evolution during the electrocatalytic process.
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The complete mitogenome sequence of Eothenomys eleusis Thomas 1911 was determined using PCR. A circular double-stranded structure makes up the mitochondrial genome of E. eleusis. The complete length of the mitochondrial genome is 16,419 bp. The mitochondrial genome of E. eleusis included 13 protein-coding genes, 1 control region, 22 tRNA genes, 2 rRNA genes and 1 origin of L strand replication. The total base composition of E. eleusis mitochondrial genome was A (32.6%), T (26.3%), G (13.6%) and C (27.5%). We found significant A-T skew in base composition, especially in control regions and protein-coding genes. E. eleusis was supported by bootstrap values of 100%. This study verifies the evolutionary status of E. eleusis in Myodini tribe of Cricetidae at the molecular level. The mitochondrial genome would be a significant supplement for the E. eleusis genetic background.
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Nanostructured metal-nitrides have attracted tremendous interest as a new generation of catalysts for electroreduction of CO2, but these structures have limited activity and stability in the reduction condition. Herein, we report a method of fabricating FeN/Fe3N nanoparticles with FeN/Fe3N interface exposed on the NP surface for efficient electrochemical CO2 reduction reaction (CO2RR). The FeN/Fe3N interface is populated with Fe-N4 and Fe-N2 coordination sites respectively that show the desired catalysis synergy to enhance the reduction of CO2 to CO. The CO Faraday efficiency reaches 98% at -0.4 V vs. reversible hydrogen electrode, and the FE stays stable from -0.4 to -0.9 V during the 100 h electrolysis time period. This FeN/Fe3N synergy arises from electron transfer from Fe3N to FeN and the preferred CO2 adsorption and reduction to *COOH on FeN. Our study demonstrates a reliable interface control strategy to improve catalytic efficiency of the Fe-N structure for CO2RR.
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Typical wide-band gap cathode interlayer materials are difficulty in reducing interface recombination without limiting charge transport in perovskite solar cells (PSCs). Here, a lead-doped titanium-oxo cluster protected by S-containing ligands is introduced at the interface of perovskite and SnO2 . By in situ heating, the cluster is transformed into PbSO4 -PbTi3 O7 heterostructure. The oxygen atoms from sulfate ion in heterostructure connect with iodine from perovskite to boost interfacial electron extraction and reduce charge recombination. While the yielded metallic interface between PbSO4 and PbTi3 O7 promotes the electron transport across the interface. Finally, an efficiency as high as 24.2 % for the modified PSC is obtained. The heterostructure well-stabilize the interface of perovskite and SnO2 , to greatly improve the device stability. This work provides a novel strategy to prepare wide-band gap cathode interlayer by directional transformation of heterometallic oxo clusters.
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ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a common systemic autoimmune disease with high morbidity and disability rate. Currently, there is no effective allopathic treatment for RA, and most of the drugs provoke many adverse effects. Simiao Yong'an decoction (SMYAD) is a traditional Chinese prescription for the treatment of sore and gangrene caused by hot poison. With the development of pharmacology and clinical research, SMYAD has remarkable anti-inflammatory properties and has been used for RA treatments for years. AIM OF THE STUDY: This study aimed to investigate the anti-arthritic effect of SMYAD and further explore the immunopharmacological mechanisms. MATERIALS AND METHODS: Arthritis was induced in DBA/1 mice by two-time immunizations. Collagen-induced rheumatoid arthritis (CIA) mice were divided into 4 groups: control, model, methotrexate (MTX), and SMYAD group (n = 6). The administration groups were given MTX (0.5 mg/kg/3 d) and SMYAD (4.5 g/kg/d) by gavage from day 14. The arthritis index (AI) score was evaluated every 3 days after the second immunization. Hematoxylin and eosin (H&E) staining, Safranin-O fast green staining, Trap staining, and Micro-CT were used to measure the histopathology injuries and bone destruction of joints. Granulocyte changes in the spleen, bone marrow, and period blood were analyzed by flow cytometry. The expression of inflammatory cytokines and chemokines in joints were detected by qRT-PCR. SMYAD-containing serum was obtained from SD rats gavaged with SMYAD. Neutrophils were isolated from peripheral blood and bone marrow for the in vitro experiments of transwell cell assay, apoptosis assay, reactive oxygen species (ROS) generation and neutrophil extracellular traps (NETs) formation. RESULTS: SMYAD significantly relieved arthritis severity in CIA mice. The AI score was significantly decreased in the SMYAD group compared with the model group. Additionally, SMYAD alleviated inflammatory infiltration, cartilage damage, osteoclast formation, and bone damage in the ankle joints. In the flow cytometry assay, SMYAD significantly reduced granulocytes number in the spleen and bone marrow, while increased in peripheral blood. Furthermore, compared with the CIA group, SMYAD suppressed the mRNA levels of inflammatory factors including TNF-α, IL-1ß, IL-6 and chemokines CXCL1, CXCL2, and IL-8 in the inflamed joints. In the in vitro studies, 20% SMYAD-containing serum effectively inhibited the migration of neutrophils, promoted neutrophils apoptosis, reduced ROS production and NETs formation. CONCLUSION: Collectively, our results demonstrated that SMYAD effectively restrained arthritis in CIA mice by modulating neutrophil activities.
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Arthrite expérimentale , Polyarthrite rhumatoïde , Souris , Rats , Animaux , Arthrite expérimentale/anatomopathologie , Granulocytes neutrophiles/métabolisme , Espèces réactives de l'oxygène , Rat Sprague-Dawley , Souris de lignée DBA , Polyarthrite rhumatoïde/traitement médicamenteux , Cytokines/métabolisme , MéthotrexateRÉSUMÉ
Pancreatic cancer is one of the most destructive malignant tumors; the pathogenesis of this disease is complex and is closely related to genetic susceptibility, chronic pancreatitis, and gene mutations in signaling pathways. The phosphoinositide 3- kinase (PI3K)/protein kinase B (Akt) signaling pathway is a classical cancer signaling pathway that is aberrantly activated in pancreatic cancer cells. In recent years, it has been found that traditional Chinese medicine (TCM) monomers show special activity in the treatment of pancreatic cancer and can be potential drug for the treatment of pancreatic cancer. Based on PI3K/Akt signaling pathway, this paper summarizes the mechanism of TCM monomer intervening in pancreatic cancer and finds that TCM monomer of alkaloids (sinomenine, dictamnine, dauricine, etc.), terpenoids (saikosaponin A, linderalactone, isoalantolactone, etc.), phenols (6-gingerol, curcumin, pterostilbene, etc.), flavonoids (fisetin, kaempferol, quercetin, etc.) and quinones (β-hydroxyisovaleryl shikonin, rhein, lucidone, etc.) can inhibit the proliferation, invasion and migration of pancreatic cancer cells, regulate autophagy and apoptosis, and then inhibit the pathological process of pancreatic cancer by inhibiting PI3K/Akt signaling pathway.
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Objective:To assess the prognostic accuracy of five scoring systems for mortality in elderly patients (≥80 years old) with sepsis.Methods:A retrospective study was conducted on elderly patients with sepsis (≥80 years old, meeting Sepsis 3.0 diagnostic criteria) in Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ). The participants were divided into survival and death group according to the 28-day mortality. The baseline data of patients was collected based on the peak of vital signs and laboratory test results within 24 hours after admission to intensive care unit (ICU). Systemic Inflammatory Response Syndrome (SIRS) score, quick Sequential Organ Failure Assessment (qSOFA), Sequential Organ Failure Assessment (SOFA), National Early Warning Score (NEWS) and Oxford Acute Severity of Illness Score (OASIS) were calculated and prognosis was recorded. The accuracy of the above scoring systems in predicting 28-day mortality was calculated, the receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUC) was calculated and compared.Results:A total of 42 037 hospital records were screened, and 956 sepsis patients (456 males, 47.70%) who were aged ≥80 years and met the Sepsis 3.0 diagnostic criteria within 24 hours of admission to ICU were included. There were 696 patients (72.8%) in the survival group and 260 patients (27.2%) in the death group. There were no significant difference in age, gender, Charlson Comorbidity Index, length of stay before admission to ICU and length of stay in ICU between 2 groups (all P>0.05). The proportion of patients receiving mechanical ventilation and septic shock in the death group were higher comparing with those in the survival group (both P<0.001), and the total length of hospital stay in the survival group was longer than that in the death group ( P<0.001). The proportion of SOFA score≥7, qSOFA score≥2, SIRS score≥2, NEWS score≥8, OASIS score≥42 in the death group was higher than that in the survival group (all P<0.05). The AUC of qSOFA, SOFA, SIRS, NEWS and OASIS in predicting the mortality of elderly sepsis patients were 0.587 (95% CI: 0.556-0.617), 0.694 (95% CI: 0.655-0.732), 0.591 (95% CI: 0.555-0.627), 0.684 (95% CI: 0.646-0.721) and 0.718 (95% CI: 0.681-0.755), respectively. Conclusions:OASIS was superior than qSOFA, SOFA, SIRS and NEWS scores in predicting the mortality of elderly patients with sepsis, but the prognostic accuracy of all above scoring systems for elderly patients with sepsis was insufficient.