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PURPOSE: To develop a PRO assessment of multidimensional cancer-related fatigue based on the PROMIS fatigue assessments. METHOD: Cancer patients reporting fatigue were recruited from a comprehensive cancer care center and completed a survey including 39 items from the PROMIS Cancer Item Bank-Fatigue. Component and factor structures of the fatigue items were explored with Monte Carlo parallel factor and Mokken analyses, respectively. Psychometric properties were determined using item response theory, ensuring unidimensionality, scalability, and item independence. RESULTS: Fatigue scores from a sample of 333 fatigued cancer patients (mean age = 59.50, SD = 11.62, 67% women) were used in all scale development analyses. Psychometric analyses yielded 3 dimensions: motivational fatigue (15 items), cognitive fatigue (9 items), and physical fatigue (9 items). The subscales showed strong unidimensionality, were scalable, and were free of differential item function. Confirmatory factor analyses in a new sample of 182 patients confirmed the findings. CONCLUSION: The resulting 33-item PROMIS multidimensional cancer-related fatigue (mCRF) form provides a novel measure for the assessment of the different dimensions of cancer-related fatigue. It is the only multidimensional scale specific for cancer patients that has been developed using modern psychometric approaches. With its 3 dimensions (motivational, cognitive, and physical fatigue), this scale accurately captures the fatigue experienced by cancer patients, allowing clinicians to optimize fatigue management and improve patient care. The scale could also advance research on the nature and experience of cancer-related fatigue.
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High-speed 3D measurement is receiving increasing attention. However, simultaneously achieving high computational efficiency, algorithmic robustness, and reconstructing ratio is challenging. Therefore, a dynamic phase-differencing profilometry (DPDP) is proposed. By capturing the minimum three phase-shifting sinusoidal deformed patterns and establishing a brand-new model, the phase difference between the object on the reference plane and the reference plane is directly resolved to effectively improve computational efficiency. Although it is wrapped, by using only two auxiliary complementary gratings with a purposely designed lower frequency, a DPDP-based number-theoretical temporal phase unwrapping (NT-TPU) algorithm is also proposed to unwrap the wrapped phase difference rather than the phase itself with high robustness. Furthermore, compared to existing PSP-based NT-TPU, the proposed NT-TPU can normally work under more relaxed restrictions. In order to accomplish a high reconstructing ratio, a pentabasic interleaved projection (PIP) strategy based on time division multiplexing is proposed. It can improve the reconstructing ratio from one reconstruction per every five patterns to an equivalent of one reconstruction per every 1.67 patterns. Experimental results demonstrate that the proposed method achieves high computational efficiency, high algorithmic robustness, and high reconstructing ratio simultaneously and has prospective application in high-speed 3D measurement.
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Numerous studies have established a correlation between social anxiety and poor cognitive control. However, little is known about the cognitive control pattern of individuals with high social anxiety (HSAs) and the underlying mechanisms. Based on the Dual Mechanisms of Control framework and the Expected Value of Control theory, this study explored whether HSAs have an impaired cognitive control pattern (Experiment 1) and whether motivational deficiencies underlie the impaired control pattern (Experiment 2). In Experiment 1, 21 individuals with low social anxiety (LSAs) and 21 HSAs completed an AX-Continuous Performance Task. Results showed that HSAs had a smaller P3b amplitude than LSAs, indicating their weakened proactive control in the cue processing stage, but a larger contingent negative variation (CNV) on cue B as compensation for the negative effects of anxiety in the response preparation stage. No group difference was found in N2 and P3a amplitude on probes, suggesting that reactive control in HSAs was not affected compared to LSAs. In Experiment 2, 21 LSAs and 21 HSAs completed a cued-flanker task, where the likelihood of proactive control engagement was manipulated. The results revealed that HSAs exhibited motivation deficiencies in engaging in proactive control, as evidenced by P3b, CNV amplitude, and response times. These findings shed light on the impaired cognitive control pattern of HSAs and suggest that motivational deficiencies may be the crucial underlying factor.
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Ansiedad , Electroencefalografía , Potenciales Evocados , Función Ejecutiva , Motivación , Humanos , Masculino , Femenino , Motivación/fisiología , Adulto Joven , Potenciales Evocados/fisiología , Adulto , Función Ejecutiva/fisiología , Ansiedad/fisiopatología , Desempeño Psicomotor/fisiología , Variación Contingente Negativa/fisiología , Adolescente , Fobia Social/fisiopatologíaRESUMEN
This study aims to conduct a cost-effectiveness analysis of three different anesthesia strategies, namely chatting while under local anesthesia (Chat-LA), total intravenous anesthesia (TIVA), and general anesthesia with laryngeal mask airway (GA-LMA), employed in transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy (TP-MUF-PB). A retrospective study was conducted involving 1202 patients who underwent TP-MUF-PB from June 2016 to April 2023 at The First Affiliated Hospital of Soochow University (Suzhou, China). Clinical data and outcomes, including total costs, complications, and quality-adjusted life years (QALYs), were compared. Probability sensitivity and subgroup analyses were also performed. Chat-LA was found to be the most cost-effective option, outperforming both TIVA and GA-LMA. However, subgroup analyses revealed that in younger patients (under 65 years old) and those with smaller prostate volumes (<40 ml), TIVA emerged as a more cost-effective strategy. While Chat-LA may generally be the most cost-effective and safer anesthesia method for TP-MUF-PB, personalization of anesthesia strategies is crucial, considering specific patient demographics such as age and prostate volume.
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Análisis Costo-Beneficio , Biopsia Guiada por Imagen , Próstata , Neoplasias de la Próstata , Humanos , Masculino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Próstata/patología , Próstata/diagnóstico por imagen , Biopsia Guiada por Imagen/métodos , Biopsia Guiada por Imagen/economía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Imagen por Resonancia Magnética/economía , Imagen por Resonancia Magnética/métodos , Anestesia Local/economía , Anestesia Local/métodos , Años de Vida Ajustados por Calidad de Vida , Anestesia General/economía , Análisis de Costo-EfectividadRESUMEN
BACKGROUND: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC). METHODS: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end point was immune-related PFS (irPFS). RESULTS: Sixty-one subjects were randomized to sequential (n = 38) or combination therapy (n = 23). Thirteen patients (34.2%) in the sequential arm received durvalumab. There was no difference in PFS in the sequential arm (1.84 months; 95% CI, 1.77-2.17 months) compared with the combination arm (1.87 months; 95% CI, 1.77-2.43 months) (p = .402). In the sequential arm, no responses were observed, although 12 patients (31.6%) demonstrated stable disease. In the combination arm, two patients (8.7%) had partial response, whereas one patient (4.4%) had stable disease. Adverse events were consistent with those previously reported for ICIs. Patient-reported outcomes were similar in both arms. CONCLUSIONS: There was no difference in irPFS for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum-resistant HGSOC. Response rates were comparable to prior reports, although the combination regimen did not add significant benefit, as has been previously described.
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Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ováricas , Humanos , Femenino , Teorema de Bayes , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Ováricas/tratamiento farmacológicoRESUMEN
OBJECTIVE: This study aimed to develop a preoperative nomogram based on clinical and pathological characteristics to provide a more individualized and accurate estimation of lymph node metastasis (LNM) in patients with early-stage cervical cancer. METHODS: A total of 7,349 early-stage cervical cancer patients with pathologically confirmed between 1988 and 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. All the patients were divided into training (n = 5,500) and validation (n = 1,849) cohorts randomly. A cohort of 455 patients from multicenter was used for the external validation. We established a multivariate logistic regression model based on preoperative clinicopathological data, from which a nomogram was developed and validated. A predicted probability of LNM < 5% was defined as low risk. RESULTS: From multivariate logistic regression analysis, age at diagnosis, histologic subtype, tumor grade, tumor size and FIGO stage were identified as preoperative independent risk factors of LNM. The nomogram incorporating these factors demonstrated good discrimination and calibration (concordance index = 0.723; 95% confidence interval (CI), 0.707-0.738). In the validation cohort, the discrimination accuracy was 0.745 (95% CI, 0.720-0.770) and 0.747 (95% CI, 0.690-0.804), respectively. The nomogram was well calibrated with a high concordance probability. We also established an R-enabled Internet browser for LNM risk assessment, which tool may be convenient for physicians. CONCLUSIONS: We developed an effective preoperative nomogram based on clinical and pathological characteristics to predict LNM for early-stage cervical cancer. This model could improve clinical trial design and help physicians to decide whether to perform lymphadenectomy or not.
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Nomogramas , Neoplasias del Cuello Uterino , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/patología , Estudios Multicéntricos como AsuntoRESUMEN
Chinese herbal medicines (CHMs) derived from nature have received increasing attention and become more popular. Due to their diverse production processes, complex ingredients, and different storage conditions, it is highly desirable to develop simple, rapid, efficient and trace detection methods to ensure the drug quality. Surface-enhanced Raman spectroscopy has the advantages of being time-saving, non-destructive, usable in aqueous environments, and highly compatible with various biomolecular samples, providing a promising analytical method for CHM. In this review, we outline the major advances in the application of SERS to the identification of raw materials, detection of bioactive constituents, characterization of adulterants, and detection of contaminants. This clearly shows that SERS has strong potential in the quality control of CHM, which greatly promotes the modernization of CHM.
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Medicamentos Herbarios Chinos , Medicamentos Herbarios Chinos/química , Espectrometría Raman/métodos , Control de Calidad , AguaRESUMEN
It is crucial to clarify the impact of land use change on ecosystem carbon sequestration service for exploring natural-based carbon neutral solutions. We used InVEST and FLUS models to analyze land use change and its impacts on ecosystem carbon sequestration service in Zhejiang Province from 2000 to 2021, and predict ecosystem carbon sequestration service potential and its economic value of land use pattern in 2035 and 2050 under three scenarios of natural development, ecological protection, and cultivated land protection. The results showed that the area of cultivated land, forest, grassland, and water was continuously reducing and the area of construction land was continuously increasing from 2000 to 2021 in Zhejiang Province. The total amount of ecosystem carbon sequestration service decreased by 29.9658 million t, and the net income of carbon sequestrqtion service was -170.7184 million dollars. The distribution of ecosystem carbon sequestration services showed a spatial pattern of high in the southwest and low in the northeast. In the future, the total amount of ecosystem carbon sequestration services in Zhejiang Province would be the highest under the ecological protection scenario, followed by the cultivated land protection scenario, and the lowest under the natural development scenario. From 2021 to 2035 and 2050, ecosystem carbon sequestration services in Zhejiang Province would increase by 3.2326 million and 4.73 million t respectively under the ecological protection scenario, generating carbon sequestration service benefits of 77.0786 million and 111.8391 million dollars, respectively. Under the cultivated land protection scenario, it would be reduced by 10.1318 million and 16.1611 million t, and the net loss of carbon sequestration service value would be 241.3849 million and 381.9109 million dollars, respectively. Under the natural development scenario, it would be reduced by 11.6490 million and 16.1651 million t, resulting in a net loss of carbon sequestration service value of 277.5393 million and 382.0063 million dollars, respectively. In the context of actively addressing climate change and striving to achieve the goal of carbon neutrality, Zhejiang Province should focus on protecting ecological land such as woodlands, grasslands, and water, expand the scale of ecological land, optimize the spatial structure of ecological land, and continuously enhance carbon sequestration and sink enhancement functions of ecological land.
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Secuestro de Carbono , Ecosistema , China , Carbono , AguaRESUMEN
Archaeal ribosomes have many domain-specific features; however, our understanding of these structures is limited. We present 10 cryo-electron microscopy (cryo-EM) structures of the archaeal ribosome from crenarchaeota Sulfolobus acidocaldarius (Sac) at 2.7-5.7 Å resolution. We observed unstable conformations of H68 and h44 of ribosomal RNA (rRNA) in the subunit structures, which may interfere with subunit association. These subunit structures provided models for 12 rRNA expansion segments and 3 novel r-proteins. Furthermore, the 50S-aRF1 complex structure showed the unique domain orientation of aRF1, possibly explaining P-site transfer RNA (tRNA) release after translation termination. Sac 70S complexes were captured in seven distinct steps of the tRNA translocation reaction, confirming conserved structural features during archaeal ribosome translocation. In aEF2-engaged 70S ribosome complexes, 3D classification of cryo-EM data based on 30S head domain identified two new translocation intermediates with 30S head domain tilted 5-6° enabling its disengagement from the translocated tRNA and its release post-translocation. Additionally, we observed conformational changes to aEF2 during ribosome binding and switching from three different states. Our structural and biochemical data provide new insights into archaeal translation and ribosome translocation.
Archaeal ribosomes display variations in their ribosomal proteins and ribosomal RNA (rRNA) expansion segments (ESs). Protein translation in archaea combines features in both bacterial and eukaryotic translation. In this study, we present 10 cryo-electron microscopy structures of the archaeal ribosome from crenarchaeota Sulfolobus acidocaldarius (Sac). The 50S and 30S subunit structures present 3 novel ribosomal proteins and 12 rRNA ESs. The 70S Sac ribosome structures were captured in seven distinct functional states, including pre-, intermediate- and post-translocation states. Specifically, we identified two novel translocation intermediates, in which the 30S subunit head domain tilts outward to release the translocated P-site transfer RNA. The structures of archaeal ribosomes provide insights into the archaeal translation and ribosome translocation.
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Ribosomas , Sulfolobus acidocaldarius , Microscopía por Crioelectrón , Proteínas Ribosómicas/metabolismo , Ribosomas/metabolismo , ARN Ribosómico/metabolismo , ARN de Transferencia/metabolismo , Sulfolobus acidocaldarius/citología , Sulfolobus acidocaldarius/metabolismoRESUMEN
The energy band structure, density of states, and optical properties of monolayers of MoS2 doped with alkaline earth metals (Be/Mg/Ca/Sr/Ba) are systematically studied based on first principles. The results indicate that all the doped systems have a great potential to be formed and structurally stable. In comparison to monolayer MoS2, doping alkaline earth metals results in lattice distortions in the doped system. Therefore, the recombination of photogenerated hole-electron pairs is suppressed effectively. Simultaneously, the introduction of dopants reduces the band gap of the systems while creating impurity levels. Hence, the likelihood of electron transfer from the valence to the conduction band is enhanced, which means a reduction in the energy required for such a transfer. Moreover, doping monolayer MoS2 with alkaline earth metals increases the static dielectric constant and enhances its polarizability. Notably, the Sr-MoS2 system exhibits the highest value of static permittivity, demonstrating the strongest polarization capability. The doped systems exhibit a red-shifted absorption spectrum in the low-energy region. Consequently, the Be/Mg/Ca-MoS2 systems demonstrate superior visible absorption properties and a favorable band gap, indicating their potential as photo-catalysts for water splitting.
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Objective: This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline (BR) and the conventional treatment regimen (CR, not containing Bedaquiline) for the treatment of adults with multidrug-resistant tuberculosis (MDR-TB) in China. Methods: A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years. The model parameter data were synthesized from the literature, the national TB surveillance information system, and consultation with experts. The incremental cost-effectiveness ratio (ICER) of BR vs. CR was determined. Results: BR ( vs. CR) had a higher sputum culture conversion rate and cure rate and prevented many premature deaths (decreased by 12.8%), thereby obtaining more quality-adjusted life years (QALYs) (increased by 2.31 years). The per capita cost in BR was as high as 138,000 yuan, roughly double that of CR. The ICER for BR was 33,700 yuan/QALY, which was lower than China's 1× per capita Gross Domestic Product (GDP) in 2020 (72,400 yuan). Conclusion: BR is shown to be cost effective. When the unit price of Bedaquiline reaches or falls below 57.21 yuan per unit, BR is expected to be the dominant strategy in China over CR.
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Antituberculosos , Tuberculosis Resistente a Múltiples Medicamentos , Adulto , Humanos , Antituberculosos/uso terapéutico , Análisis de Costo-Efectividad , Análisis Costo-Beneficio , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , China/epidemiologíaRESUMEN
Glutamine:fructose-6-phosphate aminotransferases (GFATs) and phosphofructokinase (PFKs) are the principal rate-limiting enzymes involved in hexosamine biosynthesis pathway (HBP) and glycolysis pathway, respectively. In this study, the NlGFAT and NlPFK were knocked down through RNA interference (RNAi) in Nilaparvata lugens, the notorious brown planthopper (BPH), and the changes in energy metabolism were determined. Knockdown of either NlGFAT or NlPFK substantially reduced gene expression related to trehalose, glucose, and glycogen metabolism pathways. Moreover, trehalose content rose significantly at 72 h after dsGFAT injection, and glycogen content increased significantly at 48 h after injection. Glucose content remained unchanged throughout the experiment. Conversely, dsPFK injection did not significantly alter trehalose, but caused an extreme increase in glucose and glycogen content at 72 h after injection. The Knockdown of NlGFAT or NlPFK significantly downregulated the genes in the glycolytic pathway, as well as caused a considerable and significant decrease in pyruvate kinase (PK) activity after 48 h and 72 h of inhibition. After dsGFAT injection, most of genes in TCA cycle pathway were upregulated, but after dsNlPFK injection, they were downregulated. Correspondingly, ATP content substantially increased at 48 h after NlGFAT knockdown but decreased to an extreme extent by 72 h. In contrast, ATP content decreased significantly after NlPFK was knocked down and returned. The results have suggested the knockdown of either NlGFAT or NlPFK resulted in metabolism disorders in BPHs, highlighting the difference in the impact of those two enzyme genes on energy metabolism. Given their influence on BPHs energy metabolism, developing enzyme inhibitors or activators may provide a biological control for BPHs.
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OBJECTIVES: We sought to identify trajectories of patient-reported outcomes, specifically physical well-being of the chest (PWBC), in patients who underwent postmastectomy breast reconstruction, and further assessed its significant predictors, and its relationship with health-related quality of life (HRQOL). METHODS: We used data collected as part of the Mastectomy Reconstruction Outcomes Consortium study within a 2-year follow-up in 2012-2017, with 1422, 1218,1199, and 1417 repeated measures at assessment timepoints of 0,3,12, and 24 months, respectively. We performed latent class growth analysis (LCGA) in the implant group (IMPG) and autologous group (AUTOG) to identify longitudinal change trajectories, and then assessed its significant predictors, and its relationship with HRQOL by conducting multinomial logistic regression. RESULTS: Of the included 1424 patients, 843 were in IMPG, and 581 were in AUTOG. Both groups experienced reduced PWBC at follow-up. LCGA identified four distinct PWBC trajectories (χ2 = 1019.91, p<0.001): low vs medium high vs medium low vs high baseline PWBC that was restored vs. not-restored after 2 years. In 76.63%(n = 646) of patients in IMPG and 62.99% (n = 366) in AUTOG, PWBC was restored after two years. Patients in IMPG exhibited worse PWBC at 3 months post-surgery than that in AUTOG. Patients with low baseline PWBC that did not improve at 2-year follow up (n = 28, 4.82% for AUTOG) were characterized by radiation following reconstruction and non-white ethnicity. In IMPG, patients with medium low-restored trajectory were more likely to experience improved breast satisfaction, while patients developing high-restored trajectories were less likely to have worsened psychosocial well-being. CONCLUSION: Although more women in IMPG experienced restored PWBC after 2 years, those in AUTOG exhibited a more favorable postoperative trajectory of change in PWBC. This finding can inform clinical treatment decisions, help manage patient expectations for recovery, and develop rehabilitation interventions contributing to enhancing the postoperative quality of life for breast cancer patients.
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Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Mastectomía/psicología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/psicología , Calidad de Vida , Satisfacción del Paciente , Estudios ProspectivosRESUMEN
BACKGROUND: We sought to predict clinically meaningful changes in physical, sexual, and psychosocial well-being for women undergoing cancer-related mastectomy and breast reconstruction 2 years after surgery using machine learning (ML) algorithms trained on clinical and patient-reported outcomes data. PATIENTS AND METHODS: We used data from women undergoing mastectomy and reconstruction at 11 study sites in North America to develop three distinct ML models. We used data of ten sites to predict clinically meaningful improvement or worsening by comparing pre-surgical scores with 2 year follow-up data measured by validated Breast-Q domains. We employed ten-fold cross-validation to train and test the algorithms, and then externally validated them using the 11th site's data. We considered area-under-the-receiver-operating-characteristics-curve (AUC) as the primary metric to evaluate performance. RESULTS: Overall, between 1454 and 1538 patients completed 2 year follow-up with data for physical, sexual, and psychosocial well-being. In the hold-out validation set, our ML algorithms were able to predict clinically significant changes in physical well-being (chest and upper body) (worsened: AUC range 0.69-0.70; improved: AUC range 0.81-0.82), sexual well-being (worsened: AUC range 0.76-0.77; improved: AUC range 0.74-0.76), and psychosocial well-being (worsened: AUC range 0.64-0.66; improved: AUC range 0.66-0.66). Baseline patient-reported outcome (PRO) variables showed the largest influence on model predictions. CONCLUSIONS: Machine learning can predict long-term individual PROs of patients undergoing postmastectomy breast reconstruction with acceptable accuracy. This may better help patients and clinicians make informed decisions regarding expected long-term effect of treatment, facilitate patient-centered care, and ultimately improve postoperative health-related quality of life.
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Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Mastectomía/efectos adversos , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/psicología , Calidad de Vida , Satisfacción del Paciente , Mamoplastia/efectos adversosRESUMEN
Microglia-induced neuroinflammation is a contributing factor to neurodegenerative diseases. Jatrorrhizine (JAT), an alkaloid isolated from Huanglian, has been shown to have neuroprotective effects against various neurodegenerative diseases, but its impact on microglia-induced neuroinflammation remains unclear. In this study, we investigated the role of JAT in MAPK/NF-κB/NLRP3 signaling pathway in an H2O2-induced oxidative stress model using microglia (N9 cells). We divided cells into six groups, including control, JAT, H2O2, H2O2 + 5 µmol/L JAT, H2O2 + 10 µmol/L JAT, and H2O2 + 20 µmol/L minocycline groups. Cell viability was measured using MTT assay and TNF-α levels were detected with an ELISA Kit. Western blot was used to detect NLRP3, HMGB1, NF-κB, p-NF-κB, ERK, p-ERK, p38, p-p38, p-JNK, JNK, IL-1ß, and IL-18 expressions. Our results showed that JAT intervention improved H2O2-induced cytotoxicity in N9 cells and reduced the elevated expression of TNF-α, IL-1ß, IL-18, p-ERK/ERK, p-p38/p38, p-JNK/JNK, p-p65/p65, NLRP3, and HMGB1 in H2O2 group. Furthermore, treatment with ERK inhibitor SCH772984 specifically blocked ERK phosphorylation, resulting in decreased protein levels of p-NF-κB, NLRP3, IL-1ß, and IL-18 in H2O2 group. These results suggest that the MAPK/NF-κB signaling pathway may regulate the protein levels of NLRP3. Overall, our study indicates that JAT may have a protective effect on H2O2-treated microglia via inhibition the MAPK/NF-κB/NLRP3 pathway and could be a potential therapeutic approach for neurodegenerative diseases.
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Proteína HMGB1 , FN-kappa B , Humanos , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Interleucina-18 , Proteína HMGB1/metabolismo , Peróxido de Hidrógeno/toxicidad , Factor de Necrosis Tumoral alfa , Enfermedades Neuroinflamatorias , Microglía/metabolismo , Transducción de SeñalRESUMEN
Background: The associated factors of peritoneal small solute transport was not fully understood. This research aimed to investigate the connection between dialysate inflammatory markers (e.g. macrophage migration inhibitory factor, MIF) in peritoneal dialysis (PD) effluent and peritoneal solute transport rate (PSTR) properties. Subjects and design: A total of 80 stable PD patients in the First ShaoYang Hospital were enrolled in present study. Overnight PD effluent and serum inflammatory markers including MIF, MCP-1, VEGF, IL-6, TNFα and TGFβ were detected. Pearson correlation analysis and Logistic regression was performed to determine the risk factors for the increased PSTR. Results: A trend toward increased values of MIF, MCP-1 and IL-6 in PD effluent was observed in subjects with high PSTR when compared with those with low PSTR. The Pearson correlation test showed that D/P Cr exhibited positive correlations with dialysis effluent MIF (r=0.32, p=0.01), MCP-1 (r=0.47, p=0.01), IL-6 (r=0.48, p=0.01). Conversely, no significant correlation was found between D/P Cr and TGF-β (r=0.04, p=0.70), TNF-ɑ (r=0.22, p=0.05), VEGF (r=0.02, p=0.86) and serum inflammatory markers. In the unadjusted regression analysis, dialysis effluent MIF (OR 2.41), MCP-1 (OR 1.72), IL-6 (OR 1.55) were associated with high PSTR condition. Multivariate logistic regression analysis showed that the adjusted odds ratios (OR) of dialysis effluent MIF for high PSTR were 2.47 in all subjects (p=0.03). Conclusion: Elevated MIF, MCP-1 and IL-6 levels in PD effluent were associated with increased PSTR. Elevated dialysis effluent MIF levels was an independent risk factor for high PSTR in subjects with PD treatment. (AU)
Antecedentes: Los factores asociados del transporte peritoneal de pequeños solutos no se conocen completamente. Esta investigación tuvo como objetivo investigar la conexión entre los marcadores inflamatorios del dializado (por ejemplo, el factor inhibidor de la migración de macrófagos [MIF]) en el efluente de diálisis peritoneal (DP) y las propiedades de la tasa de transporte de solutos peritoneal (PSTR). Sujetos y diseño: Se incluyó un total de 80 pacientes con DP estable en el primer Hospital de Shaoyang. Se detectaron efluentes de DP nocturnos y marcadores inflamatorios séricos, incluyendo MIF, MCP-1, VEGF, IL-6, TNF -ɑ, TGF -β. Se realizó un análisis de correlación de Pearson y regresión logística para determinar los factores de riesgo para la PSTR aumentada. Resultados: Se observó una tendencia hacia valores incrementados de MIF, MCP-1 e IL-6 en el efluente de DP en sujetos con PSTR alta, en comparación con aquellos con PSTR baja. La prueba de correlación de Pearson mostró que D/Pcr exhibe correlaciones positivas con el MIF del efluente diálisis (r = 0,32, p = 0,01), MCP-1 (r = 0,47, p = 0,01), IL-6 (r = 0,48, p = 0,01). Por el contrario, no se encontró una correlación significativa entre D/Pcr y TGF-β (r = 0,04, p = 0,70), TNF-ɑ (r = 0,22, p = 0,05), VEGF (r = 0,02, p = 0,86) y marcadores séricos de inflamación. En el análisis de regresión no ajustado, el MIF del efluente diálisis (OR 2,41), la MCP-1 (OR 1,72), la IL-6 (OR 1,55) se asociaron con una PSTR elevada. El análisis de regresión logística multivariante mostró que las odds ratios (OR) ajustadas del MIF del efluente diálisis para PSTR alta fueron de 2,47 en todos los sujetos (p = 0,03). Conclusión: Los niveles elevados de MIF, MCP-1 y IL-6 en el efluente de DP se asociaron con un aumento de la PSTR. Los niveles elevados del MIF del efluente diálisis fueron un factor de riesgo independiente para PSTR elevada en sujetos tratados con DP. (AU)
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Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Diálisis Peritoneal , Factores Inhibidores de la Migración de Macrófagos , Proteínas Transportadoras de Solutos , Estudios Transversales , ChinaRESUMEN
OBJECTIVE: To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS: This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS: The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION: CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.
Asunto(s)
Adenomiosis , Endometriosis , Embarazo , Femenino , Humanos , Adulto , Resultado del Embarazo , Endometriosis/complicaciones , Endometriosis/tratamiento farmacológico , Endometriosis/cirugía , Estudios Retrospectivos , Estudios de Cohortes , Hormona Liberadora de Gonadotropina , Extractos Vegetales , Fertilización In VitroRESUMEN
The selective CH bond oxidation of aromatic hydrocarbon is an interesting but challenging task, it is desirable to develop efficient heterogeneous non-noble metal catalyst for this reaction. Herein, two kinds of spinel (FeCoNiCrMn)3O4 high entropy oxides were fabricated via two different methods (i.e., c-FeCoNiCrMn, prepared by a co-precipitation method, and m-FeCoNiCrMn, prepared by physically mixing method). Different from traditional environmentally-unfriendly Co/Mn/Br system, the prepared catalysts were employed for the selective CH bond oxidation of p-chlorotoluene to p-chlorobenzaldehyde in a green approach. Compared to m-FeCoNiCrMn, c-FeCoNiCrMn have smaller particles size and larger specific surface area, which were related to the enhanced catalytic activity. More importantly, characterization results disclosed that abundant oxygen vacancies were formed over c-FeCoNiCrMn. Such a result facilitated the adsorption of p-chlorotoluene on the catalyst surface and promoted the formation of *ClPhCH2O intermediate as well as the desired p-chlorobenzaldehyde, as revealed by DFT (Density functional theory) calculations. Besides, scavenger tests and EPR (Electron paramagnetic resonance) results indicated that hydroxyl radical derived from H2O2 homolysis was the main active oxidative species for this reaction. This work revealed the role of oxygen vacancy in spinel high entropy oxide and also demonstrated its promising application for the selective CH bond oxidation in an environmentally-benign approach.