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Studies of forces driving interlineage variability in the evolutionary rates (both sequence and architecture) of mitochondrial genomes often produce contradictory results. Flatworms (Platyhelminthes) exhibit the fastest-evolving mitogenomic sequences among all bilaterian phyla. To test the effects of multiple factors previously associated with different aspects of mitogenomic evolution, we used mitogenomes of 223 flatworm species, phylogenetic multilevel regression models, and causal inference. Thermic host environment (endothermic vs. ectothermic) had nonsignificant impacts on both sequence evolution and mitogenomic size. Mitogenomic gene order rearrangements (GORR) were mostly positively correlated with mitogenomic size (R2 ≈ 20-30%). Longevity was not (negatively) correlated with sequence evolution in flatworms. The predominantly free-living "turbellaria" exhibited much shorter branches and faster-evolving mitogenomic architecture than parasitic Neodermata. As a result, "parasitism" had a strong explanatory power on the branch length variability (>90%), and there was a negative correlation between GORR and branch length. However, the stem branch of Neodermata comprised 63.6% of the total average branch length. This evolutionary period was also marked by a high rate of gene order rearrangements in the ancestral Neodermata. We discuss how this period of rapid evolution deep in the evolutionary history may have decoupled sequence evolution rates from longevity and GORR, and overestimated the explanatory power of "parasitism". This study shows that impacts of variables often vary across lineages, and stresses the importance accounting for the episodic nature of evolutionary patterns in studies of mitogenomic evolution.
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Objective: Examining the current situation of test anxiety among first year senior high school students in Yanji City and investigating the factors that contribute to exam anxiety. Methods: Using cluster sampling, a survey was conducted on 1,550 first-year high school students from three high schools in Yanji City in April-May 2023. The survey utilized general information questionnaires, the Minnesota Multiphasic Personality Inventory (MMPI), and the Self-Rating Anxiety Scale (SAS). Logistic regression analysis was used to determine the influencing factors of test anxiety. Results: A total of 1,550 first-year high school students were included in the analysis, with a test anxiety occurrence rate of 79.8%. Test anxiety exhibited statistical differences among different genders, ethnicities, family economic levels, frequency of communication with parents, and relationships with parents (with results of 53.44, 10.42, 17.31, 20.42, 31.95, all p < 0.05). Scores of hypochondriasis (Hs), depression (D), psychasthenia (Pt), paranoia (Pa), psychopathic deviate (Pd), schizophrenia (Sc), and hypomania (Ma) in the 10 clinical personality scales were significantly positively correlated. Logistic regression analysis revealed that gender, ethnicity, frequency of communication with parents, and scores of hypochondriasis (Hs), depression (D), psychasthenia (Pt), paranoia (Pa), and hypomania (Ma) in the 10 clinical personality scales were the main influencing factors for test anxiety in first-year high school students (all p < 0.05). Conclusion: The test anxiety level of high school students in Yanji City is relatively high, with variations in test anxiety levels among students of different genders, ethnicities, parental communication styles, and deviant personality traits. It is recommended that schools and teachers should give more consideration to test anxiety among high school students, particularly targeting those with potential risk factors. Parents should also be more attentive to their children's development and advancement, and improve their family education principles.
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BACKGROUND: Insomnia disorder (ID) is one of the most common sleep problems, usually accompanied by anxiety and depression symptoms. Functional magnetic resonance imaging (fMRI) study suggests that both poor sleep quality and negative emotion are linked to the dysregulation of brain network related to emotion processing in ID patients. Acupuncture therapy has been proven effective in improving sleep quality and mood of ID patients, but the involved neurobiological mechanism remains unclear. We aimed to investigate the modulation effect of acupuncture on resting-state functional connectivity (rsFC) of the emotional network (EN) in patients experiencing insomnia. METHODS: A total of 30 healthy controls (HCs) and 60 ID patients were enrolled in this study. Sixty ID patients were randomly assigned to real and sham acupuncture groups and attended resting-state fMRI scans before and after 4 weeks of acupuncture treatment. HCs completed an MRI/fMRI scan at baseline. The rsFC values within EN were calculated, and Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), Hyperarousal Scale (HAS), and actigraphy data were collected for clinical efficacy evaluation. RESULTS: Resting-state FC analysis showed abnormalities in rsFC centered on the thalamus and dorsolateral prefrontal cortex within EN of ID patients compared to HCs. After real acupuncture treatment, rsFC of the anterior cingulate cortex, hippocampus, and amygdala were increased compared with the sham acupuncture group (p < 0.05, FDR corrected). In real acupuncture group, the rsFC value was decreased between left amygdala and left thalamus after 4 weeks of treatment compared with baseline. A trend of correlation was found that the increased rsFC value between the right amygdala and left hippocampus was positively correlated with the decreased HAMA scores across all ID patients, and the decreased left amygdala rsFC value with the left thalamus was negatively correlated with the increased sleep efficiency in the real acupuncture group. CONCLUSION: Our findings showed that real acupuncture could produce a positive effect on modulating rsFC within network related to emotion processing in ID patients, which may illustrate the central mechanism underlying acupuncture for insomnia in improving sleep quality and emotion regulation. TRIAL REGISTRATION: http://www.chictr.org.cn ., ChiCTR1800015282, 20/03/2018.
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Terapia por Acupuntura , Imagen por Resonancia Magnética , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Emociones , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagenRESUMEN
One of the main characteristics of diabetic kidney disease (DKD) is abnormal renal tubular fatty acid metabolism, especially defective fatty acid oxidation (FAO), accelerating tubular injury and tubulointerstitial fibrosis. Thiosulfate sulfurtransferase (TST), a mitochondrial enzyme essential for sulfur transfer, is reduced in metabolic diseases like diabetes and obesity. However, the potential role of TST in regulating fatty acid metabolic abnormalities in DKD remains unclear. Here, our data revealed decreased TST expression in the renal cortex of DKD patients. TST deficiency exacerbated tubular impairment in both diabetic and renal fibrosis mouse models, while sodium thiosulfate treatment or TST overexpression mitigated renal tubular injury with high-glucose exposure. TST downregulation mediated the decrease in S-sulfhydration of very long-chain specific acyl-CoA dehydrogenase, resulting in mitochondrial FAO dysfunction. This sequence of events exacerbates the progression of tubulointerstitial injury in DKD. Together, our findings demonstrate TST as a regulator of renal tubular injury in DKD.
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OBJECTIVES: The aim of the present meta-analysis was to compare the efficacy and safety of the carbon fiber-reinforced polyetheretherketone (CFR-PEEK) and titanium plate for the treatment of proximal humeral fractures (PHFs) from clinical comparative trials. MATERIALS AND METHODS: A comprehensive search of English databases was carried out, such as PubMed, Web of Science, ScienceDirect, Springer and Cochrane Library databases. The RevMan version 5.1 software was applied for statistical analysis, and the mean difference (MD) and risk difference (RD) as the combined variables, and "95%" as the confidence interval (CIs). RESULTS: One randomized-controlled trial and five retrospective controlled studies including 282 PHFs were considered eligible and finally included. Meta-analysis demonstrated that there were significant differences in Constant score (CS) (MD=9.23; 95% CI: 5.02, 13.44; p<0.0001), anterior elevation (MD=18.83; 95% CI: 6.27, 31.38; p=0.003), lateral elevation (MD=18.42; 95% CI: 3.64, 33.19; p=0.01) and adduction (MD=3.53; 95% CI: 0.22, 6.84; p=0.04). No significant differences were observed regarding Constant score compared to the contralateral shoulder, Oxford Shoulder Score, internal rotation, external rotation, screw perforation and cutout, varus/valgus malalignment, humeral head collapse/necrosis, implant removal, and revision surgery between the two groups. CONCLUSION: Compared to titanium plate, CFR-PEEK plate showed better Constant score, anterior elevation, lateral elevation and adduction in treating PHFs. The complications are comparable to those achieved with conventional titanium plates.
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Benzofenonas , Placas Óseas , Fibra de Carbono , Fijación Interna de Fracturas , Cetonas , Polietilenglicoles , Polímeros , Fracturas del Hombro , Titanio , Humanos , Fracturas del Hombro/cirugía , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Resultado del Tratamiento , CarbonoRESUMEN
BACKGROUND: Reduced effective circulating blood volume and impaired peripheral tissue perfusion play an important role in the pathophysiology of shock. However, there have been no studies examining the relationship between Doppler ultrasound of the superior mesenteric artery (SMA) under different shock conditions. METHODS: We evaluated a total of 85 patients, including 63 patients with different types of shock and 22 in the control group. we included patients who were diagnosed with shock upon admission or developed shock during their hospital stay. At the same time, patients with stable hemodynamics, no use of vasoactive drugs and normal lactate levels were used as a control group. We collected SMA Doppler ultrasound parameters, including Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), Resistance Index (RI), pulsatility index (PI), Time-Averaged Mean Velocity (TAMV), and Blood Flow (BF). RESULTS: In the cardiac shock group, SMA PSV, TAMV, and BF were lower compared to the other groups. There was no significant difference in SMA RI and PI between the different types of shock groups, but both were significantly lower than the control group. Cardiac index (CI) is correlated with SMA PSV (râ¯=â¯0.487, Pâ¯=â¯0.000) and TAMV (râ¯=â¯0.538, Pâ¯=â¯0.000), whereas SVRI is not correlated with SMA RI and PI. Lactate levels was correlation with SMA RI (râ¯=â¯-0.307, Pâ¯=â¯0.000) and PI (râ¯=â¯-0.287, Pâ¯=â¯0.000). The area under the ROC curve of SMA RI and PI to predict hyperlactatemia was 0.85[0.78-0.91] and 0.83[0.76-0.90]. CONCLUSIONS: The velocity parameters of SMA Doppler ultrasound such as TAMV and PSV can reflect cardiac function. The measurements of SMA RI and PI are correlated with lactate levels, having a positive predictive value for hyperlactatemia and provide guidance for fluid resuscitation in patients with shock in the future.
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The vast extensional planes of two-dimensional (2D) nanomaterials are recognized as desirable ground for electrocatalytic reactions. However, they tend to exhibit catalytic inertia due to their surface-ordered coordination configurations. Herein, an in situ autoxidation strategy enables high-density grafting of ultrafine CeO2 nanoclusters on 2D Co(OH)2. Affluent active units were activated at the inert interface of Co(OH)2 via the formation of Co-O-Ce units. The optimized catalyst exhibits oxygen evolution reaction activity with an overpotential of 83 mV lower than that of Co(OH)2 at 10 mA cm-2. The cascade orbital coupling between Co (3d) and Ce (4f) in Co-O-Ce units drives electron transfer by unlocking a "d-f electron ladder". Meanwhile, the bond-order theorem analyses and the d-band center show that the occupancy of Co-3d-eg is optimized to balance the adsorption-desorption process of active sites to the key reaction intermediate *OOH, thereby making it easier to release oxygen. This work will drive the development of wider area electron modulation methods and provide guidance for the surface engineering of 2D nanomaterials.
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CONTEXT: The mechanisms for the formation of the first C - C bond and lower olefins on methanol to olefins (MTO) conversion on H-ZSM-5 had been focused in dispute. In this paper, density functional theory has been used to study the reaction mechanisms of methanol to olefins on ZSM-5. The configurations of reactants, intermediates, products and transition state of the numerous reactions involved in such a process have been optimized, as well as the elementary reactions related to these configurations were determined by the calculation of corresponding activation energy barriers and reaction heats. Here, two different kinds of the mechanisms were proposed for the formation of dimethyl ether (DME), one involving an associative interaction of two methanol molecules with the zeolite Brønsted acid sites and the other occurring via a surface methoxy species and a methanol molecule. A critical intermediate of the methoxy methyl cation was theoretically verified by the reaction of the methoxy species and dimethyl ether. Besides, it was found that the first intermediates containing a C - C bond were 1,2-dimethoxyethane and 2-methoxy-ethanolare, in which the former was formed from methoxy species with dimethyl ether and the latter was formed from methanol by onium ions((CH3)2O+CH2CH2OCH3), respectively. For the whole reaction mechanism, the results in this paper indicated that the ethene formation is more favorable than propylene formation due to the low activation energy barrier for ethene formation (123.49 vs. 162.09 kJ.mol-1). From these calculations, it would be concluded that ethene is the first alkene product that induces the occurrence of the hydrocarbon pool mechanism. METHODS: All the periodic density function theory (DFT) calculations were performed by the Vienna Ab Initio Simulation package (VASP). The interaction between nucleus and valence electron was described using the pseudopotentials found in the projector augmented wave (PAW) method. PBE-D3 was used in the whole DFT calculations and CI-NEB was used to locate transition state.
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Bacterial intestinal inflammation frequently occurs in cultured fish. Nevertheless, research on intestinal barrier dysfunction in the process of intestinal inflammation is deficient. In this study, we explored the changes of intestinal inflammation induced by Aeromonas hydrophila (A. hydrophila) in snakehead and the relationship between intestinal barrier and inflammation. Snakehead [(13.05 ± 2.39) g] were infected via anus with A. hydrophila. Specimens were collected for analysis at 0, 1, 3, 7 and 21 d post-injection. The results showed that with the increase of exposure time, the hindgut underwent stages of normal function, damage, damage deterioration, repair and recovery. Relative to 0 d, the levels of IL-1ß and TNF-α in serum, and the expression of nod1, tlr1, tlr5, nf-κb, tnf-α and il-1ß in intestine were significantly increased, and showed an upward then downward pattern over time. However, the expression of tlr2 and il-10 were markedly decreased, and showed the opposite trend. In addition, with the development of intestinal inflammation, the diversity and richness of species, and the levels of phylum and genus in intestine were obviously altered. The levels of trypsin, LPS, AMS, T-SOD, CAT, GPx, AKP, LZM and C3 in intestine were markedly reduced, and displayed a trend of first decreasing and then rebounding. The ultrastructure observation showed that the microvilli and tight junction structure of intestinal epithelial cells experienced normal function initially, then damage, and finally recovery over time. The expression of claudin-3 and zo-1 in intestine were significantly decreased, and showed a trend of first decreasing and then rebounding. Conversely, the expression of mhc-i, igm, igt and pigr in intestine were markedly increased, and displayed a trend of increasing first and then decreasing. The above results revealed the changes in intestinal barrier during the occurrence and development of intestinal inflammation, which provided a theoretical basis for explaining the relationship between the two.
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Aeromonas hydrophila , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Intestinos , Animales , Aeromonas hydrophila/fisiología , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/microbiología , Peces/inmunología , Peces/microbiología , Microbioma Gastrointestinal , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Inflamación/inmunología , Inflamación/veterinaria , Mucosa Intestinal/inmunología , Intestinos/inmunología , Intestinos/patologíaRESUMEN
Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Quimiocina CCL20 , Neoplasias Pulmonares , FN-kappa B , Proteína 2 Ligando de Muerte Celular Programada 1 , Linfocitos T Reguladores , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Humanos , FN-kappa B/metabolismo , Animales , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Proteína 2 Ligando de Muerte Celular Programada 1/metabolismo , Proteína 2 Ligando de Muerte Celular Programada 1/genética , Quimiocina CCL20/metabolismo , Quimiocina CCL20/genética , Ratones , Fumar Tabaco/efectos adversos , Transducción de Señal , Línea Celular Tumoral , Masculino , FemeninoRESUMEN
BACKGROUND: Chemotherapeutic agents including cisplatin, gemcitabine, and pemetrexed, significantly enhance the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) by increasing PD-L1 expression and potentiating T cell cytotoxicity. However, the low response rate and adverse effects limit the application of chemotherapy/ICI combinations in patients. METHODS: We screened for medicinal herbs that could perturb PD-L1 expression and enhance T cell cytotoxicity in the presence of anti-PD-L1 antibody, and investigated the underlying mechanisms. RESULTS: We found that the aqueous extracts of Centipeda minima (CM) significantly enhanced the cancer cell-killing activity and granzyme B expression level of CD8+ T cells, in the presence of anti-PD-L1 antibody. Both CM and its active component 6-O-angeloylplenolin (6-OAP) upregulated PD-L1 expression by suppressing GSK-3ß-ß-TRCP-mediated ubiquitination and degradation. CM and 6-OAP significantly enhanced ICI-induced reduction of tumor burden and prolongation of overall survival of mice bearing NSCLC cells, accompanied by upregulation of PD-L1 and increase of CD8+ T cell infiltration. CM also exhibited anti-NSCLC activity in cells and in a patient-derived xenograft mouse model. CONCLUSIONS: These data demonstrated that the induced expression of PD-L1 and enhancement of CD8+ T cell cytotoxicity underlay the beneficial effects of 6-OAP-rich CM in NSCLCs, providing a clinically available and safe medicinal herb for combined use with ICIs to treat this deadly disease.
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Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Animales , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/farmacología , Antígeno B7-H1/metabolismo , Línea Celular Tumoral , Linfocitos T CD8-positivos/efectos de los fármacos , Ratones , Extractos Vegetales/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , FemeninoRESUMEN
BACKGROUND: Acute lung injury (ALI) can cause multiple organ dysfunction and a high mortality rate. Inflammatory responses, oxidative stress, and immune damage contribute to their pathogenic mechanisms. We studied the role of the newly discovered lncRNA, Lncmir155hg, in ALI. METHODS: The levels of Lncmir155hg and miR-450b-5p from mice with ALI were detected via polymerase chain reaction analysis (qRT-PCR) and Fluorescence in situ hybridization (FISH). Pathological changes of lung were detected by HE (hematoxylin and eosin) staining, and HIF-1α, NOD-like receptor 3 (NLRP3) and caspase-1 protein changes were detected by immunohistochemistry. MLE-12 cells proliferation was detected by Cell-Counting Kit 8 analysis, and reactive oxygen species (ROS) was detected via flow cytometry. NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 were measured via western blotting, and enzyme-linked immunosorbent assays detected the expression of Inflammatory factors. Lncmir155hg, miR-450b-5p, miR-450b-5p, and HIF-1α targets were predicted using LncTar and miRWalk and confirmed in dual-luciferase reporter assays. RESULTS: In mice with ALI and MLE-12 cells induced by lipopolysaccharide (LPS), Lncmir155hg was high-expressed and miR-450b-5p was low-expressed. sh-Lncmir155hg reduced the damage of lung tissue, the production of inflammatory cytokines and oxidative stress reaction induced by LPSï¼miR-450b-5p reverses the effect of Lncmir155hg in mice. sh-Lncmir155hg decreased the protein levels of HIF-1α, NLRP3 and caspase-1 in LPS-induced lung tissues. sh-Lncmir155hg + miR-450b-5p inhibitor transfection reversed the effect of sh-Lncmir155hg on the expression of HIF-1α, NLRP3 and caspase-1. Lncmir155hg knockdown induced proliferation and inhibited NLRP3-inflammasome activation and oxidative stress in MLE-12 cells of ALI. miR-450b-5p was identified to have binding with Lncmir155hg, and inhibition of miR-450b-5p eliminated the effect of si-Lncmir155hg in MLE-12 cells of ALI. More importantly, miR-450b-5p was directly combined with HIF-1α, miR-450b-5p mimic promoted proliferation and inhibited activation of inflammasome associated proteins and reaction of oxidative stress, and HIF-1α overexpression abolished these effects. CONCLUSION: Lncmir155hg aggravated ALI via the miR-450b-5p/HIF-1α axis.
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Lesión Pulmonar Aguda , Subunidad alfa del Factor 1 Inducible por Hipoxia , Inflamasomas , MicroARNs , Proteína con Dominio Pirina 3 de la Familia NLR , Estrés Oxidativo , ARN Largo no Codificante , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , MicroARNs/genética , MicroARNs/metabolismo , Ratones , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Inflamasomas/metabolismo , Inflamasomas/genética , Masculino , Regulación de la Expresión Génica , Lipopolisacáridos/toxicidad , Apoptosis/genética , Ratones Endogámicos C57BL , Proliferación Celular , Especies Reactivas de Oxígeno/metabolismo , Caspasa 1/genética , Caspasa 1/metabolismo , Línea Celular , Modelos Animales de Enfermedad , HumanosRESUMEN
This study aims to investigate the mechanism of Huangqin Qingre Chubi Capsules(HQC) in delaying chondrocyte senescence of osteoarthritic(OA) rats by regulating the p53/p21 signaling pathway. Rheumatic fever paralysis models of OA rats were induced based on monosodiun iodoacetate(MIA) combined with external rheumatic fever environmental stimuli and divided into normal(Con) group, OA model(MIA) group, OA model+rheumatic fever stimulation model(MIA-M) group, MIA-M+HQC low-dose(MIA-M+HQC-L) group, medium-dose(MIA-M+HQC-M) group, and high-dose(MIA-M+HQC-H) group, and MIA-M+glucosamine(MIA-M+GS) group. The models were successfully prepared and administered by gavage for 30 d. The pathological changes of cartilage were observed by hematoxylin-eosin(HE) and Senna O solid green(SO) staining. The expression of interleukin(IL)-1ß and IL-6 was detected by enzyme-linked immunosorbent assay(ELISA). Flow cytometry(FCM) was used to detect apoptosis and cell cycle. The mRNA expression of MMP13, ADAMTS-5, COLâ ¡, and TGF-ß was detected by RT-qPCR. The protein expression of p53/p21, p16, Bax, and Bcl-2 was detected by Western blot. The articular cartilage surface of rats in the Con group was smooth, and the tide line was smooth. The cartilage layer of MIA and MIA-M groups was obviously damaged, and the cartilage matrix was reduced. The above conditions were more severe in the MIA-M group. The cartilage surface of the HQC high-dose group and MIA-M+GS group was basically intact with clear delamination. Compared with the MIA-M+HQC-H group, Mankin's score was higher in the HQC low-dose and medium-dose groups, and the change was not obvious in the MIA-M+GS group. Compared with the Con group, the proportion of chondrocytes G_1 was elevated in the MIA and MIA-M groups, and the proportion of the S phase and G_2 phase was significantly decreased. In addition, the apoptosis rate was increased. Compared with MIA-M, HQC groups inhibited apoptosis and promoted cell proliferation in a concentration-dependent manner. Compared with the MIA-M+HQC-H group, the effect was more significant in the HQC high-dose group than in the HQC medium-low dose, while it was not significant in the MIA-M+GS group. Compared with the Con group, IL-1ß and IL-6 were elevated in the MIA and MIA-M groups, and mRNA levels of MMP13 and ADAMTS-5 were elevated. p53, p21, p16, and Bax protein were elevated, and mRNA levels of COLâ ¡ and TGF-ß were decreased. Compared with the MIA-M group, IL-1ß and IL-6 decreased after drug interventions of HQC and GS, and mRNA levels of MMP13 and ADAMTS-5, as well as protein levels of p53, p21, Bax, and p16 decreased. In addition, Bcl-2 increased. The improvement of these indexes was significantly better in the MIA-M+HQC-H group than in the HQC low-dose and medium-dose groups, and the difference with the MIA-M+GS group was not significant. HQC delayed MIA-induced chondrocyte senescence in OA rats, inhibited inflammatory response and extracellular matrix(ECM) degradation, and its mechanism may be related to the inhibition of the p53/p21 pathway.
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Condrocitos , Medicamentos Herbarios Chinos , Osteoartritis , Ratas Sprague-Dawley , Transducción de Señal , Proteína p53 Supresora de Tumor , Animales , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Osteoartritis/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/genética , Ratas , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Masculino , Senescencia Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Cápsulas , Humanos , Apoptosis/efectos de los fármacosRESUMEN
Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease. Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes. With the development of immunological technology, many studies have shown that diabetic nephropathy is an immune complex disease, and that most patients have immune dysfunction. However, the immune response associated with diabetic nephropathy and autoimmune kidney disease, or caused by ischemia or infection with acute renal injury, is different, and has a com-plicated pathological mechanism. In this review, we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism, to provide guidance and advice for early intervention and treatment of diabetic nephropathy.
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Surgical site infections (SSIs) related to implants have always been a major challenge for clinical doctors and patients. Clinically, doctors may directly apply antibiotics into the wound to prevent SSIs. However, this strategy is strongly associated with experience of doctors on the amount and the location of antibiotics. Herein, an in situ constructable sol-gel system is developed containing antibiotics during surgical process and validated the efficacy against SSIs in beagles. The system involves chitosan (CS), ß-glycerophosphate (ß-GP) and vancomycin (VAN), which can be adsorbed onto porous hydroxyapatite (HA) and form VAN-CS/ß-GP@HA hydrogel in a short time. The VAN concentration from VAN-CS/ß-GP@HA hydrogel is higher than minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) at the 21st day in vitro. In an in vivo canine model for the prevention of SSIs in the femoral condyle, VAN-CS/ß-GP@HA exhibits excellent biocompatibility, antimicrobial properties, and promotion of bone healing. In all, the CS/ß-GP instant sol-gel system is able to in situ encapsulate antibiotics and adhere on artificial bone implants during the surgery, effectively preventing SSIs related to implants.
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BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.
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Neoplasias Colorrectales , Tromboembolia Venosa , Humanos , Femenino , Masculino , Neoplasias Colorrectales/cirugía , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , China , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Factores de Riesgo , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Vías Clínicas , Guías de Práctica Clínica como AsuntoRESUMEN
Dry reforming of methane (DRM) reaction has great potential in reducing the greenhouse effect and solving energy problems. Herein, the DRM reaction mechanism and activity on Ni16/LaZrO2 catalyst under electric fields were comprehensively investigated by combining density functional theory calculations with microkinetic modeling. The results showed that La doping increases the interaction between Ni and ZrO2 by Ni cluster transfer of more electrons. The adsorption strength of species followed the order Ni16/ZrO2 > Ni16/LaZrO2, which is consistent with the results for the d-band center but opposite to the metal-support interaction. The best DRM reaction path on Ni16/LaZrO2 was the CH2-O pathway, which is different from the CH-O pathway on Ni(111) and Ni16/ZrO2. Both positive and negative electric fields of strong and weak metal-support interactions reduced the energy barrier of DRM reaction. Importantly, our results showed that the more dispersed and smaller Ni12/LaZrO2 model by considering the dispersing effect induced by La doping, which displayed very different results from that of Ni16/LaZrO2: reduced the energy barrier for methane decomposition, thereby promoting DRM reaction activity. Microkinetic results showed that the carbon deposition behavior of DRM becomes weaker on Ni16/LaZrO2 due to the suppression of methane decomposition in the presence of La doping compared to Ni16/ZrO2, but the opposite result is obtained on Ni12/LaZrO2. The order of DRM reactivity was Ni16/LaZrO2 < Ni16/ZrO2 < Ni12/LaZrO2, which is consistent with the experiment observations. The conversion of methane and CO2 was higher in positive electric fields than in negative electric fields at low temperatures, but the results were opposite at high temperature. Negative electric fields can improve the carbon deposition resistance of Ni-based catalysts compared to positive electric fields. The degree of rate control analysis showed that CHx* oxidation also plays an important role in the DRM reaction. We envision that this study could provide a deeper understanding for guiding the widespread application of electric field catalysis.
RESUMEN
The incidence and clinical distribution of intracranial haemorrhage (ICH) in neonates at risk of cerebral hypoxia-ischaemia have not been reported in specific studies. Based on conventional magnetic resonance imaging (MRI) versus susceptibility weighted imaging (SWI), this study aimed to analyse the occurrence of asymptomatic ICH in newborns with or without risk of cerebral hypoxia-ischaemia and to accumulate objective data for clinical evaluations of high-risk neonates and corresponding response strategies. 317 newborns were included. MRI revealed that the overall incidence of ICH was 59.31%. The most common subtype was intracranial extracerebral haemorrhage (ICECH) which included subarachnoid haemorrhage (SAH) and subdural haemorrhage (SDH). ICECH accounted for 92.02% of ICH. The positive detection rate of ICECH by SWI was significantly higher than that by T1WI. The incidence of total ICH, ICECH and SAH was greater among children who were delivered vaginally than among those who underwent caesarean delivery. Asymptomatic neonatal ICH may be a common complication of the neonatal birth process, and SWI may improve the detection rate. Transvaginal delivery and a weight greater than 2500 g were associated with a high incidence of ICECH in neonates. The impact of neonatal cerebral hypoxia-ischaemia risk factors on the occurrence of asymptomatic ICH may be negligible.