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Since October 2023, a significant outbreak of Mycoplasma Pneumoniae Pneumonia (MPP) has been observed in children in northern China. Chinese health authorities have attributed this epidemiological to immune debt resulting from the relaxation of coronavirus disease 2019 (COVID-19) control measures. This study described the epidemiological features of Mycoplasma pneumoniae (MP) prevalence in children and developed a straightforward prediction model to differentiate between MPP and viral pneumonia in children. The infection rate of MP in children notably increased from 8.12 in 2022 to 14.94% in 2023, peaking between October and November, especially among school-age children. Logistic regression screening identified four key indicators: Age, D-Dimer levels, erythrocyte sedimentation rate, and gender. The developed nomogram exhibited a receiver operator characteristic curve-area under the curve (ROC-AUC) of 0.858, with external validation confirming an ROC-AUC of 0.794. This study examined the epidemiological characteristics of MPP prevalence in children in Shandong Province during and after the COVID-19 pandemic. An early predict model was developed and validated to differentiate between Mycoplasma Pneumoniae and viral infections.
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COVID-19 , Mycoplasma pneumoniae , Neumonía por Mycoplasma , Humanos , Neumonía por Mycoplasma/epidemiología , COVID-19/epidemiología , China/epidemiología , Niño , Femenino , Masculino , Preescolar , Adolescente , Lactante , Brotes de Enfermedades , Prevalencia , SARS-CoV-2/aislamiento & purificación , Curva ROCRESUMEN
Introduction: Rapid and accurate estimation of leaf area index (LAI) is of great significance for the precision agriculture because LAI is an important parameter to evaluate crop canopy structure and growth status. Methods: In this study, 20 vegetation indices were constructed by using cotton canopy spectra. Then, cotton LAI estimation models were constructed based on multiple machine learning (ML) methods extreme learning machine (ELM), random forest (RF), back propagation (BP), multivariable linear regression (MLR), support vector machine (SVM)], and the optimal modeling strategy (RF) was selected. Finally, the vegetation indices with a high correlation with LAI were fused to construct the VI-fusion RF model, to explore the potential of multi-vegetation index fusion in the estimation of cotton LAI. Results: The RF model had the highest estimation accuracy among the LAI estimation models, and the estimation accuracy of models constructed by fusing multiple VIs was higher than that of models constructed based on single VIs. Among the multi-VI fusion models, the RF model constructed based on the fusion of seven vegetation indices (MNDSI, SRI, GRVI, REP, CIred-edge, MSR, and NVI) had the highest estimation accuracy, with coefficient of determination (R2), rootmean square error (RMSE), normalized rootmean square error (NRMSE), and mean absolute error (MAE) of 0.90, 0.50, 0.14, and 0.26, respectively. Discussion: Appropriate fusion of vegetation indices can include more spectral features in modeling and significantly improve the cotton LAI estimation accuracy. This study will provide a technical reference for improving the cotton LAI estimation accuracy, and the proposed method has great potential for crop growth monitoring applications.
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Listening to music is a promising and accessible intervention for alleviating symptoms of major depressive disorder. However, the neural mechanisms underlying its antidepressant effects remain unclear. In this study on patients with depression, we used auditory entrainment to evaluate intracranial recordings in the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc), along with temporal scalp electroencephalogram (EEG). We highlight music-induced synchronization across this circuit. The synchronization initiates with temporal theta oscillations, subsequently inducing local gamma oscillations in the BNST-NAc circuit. Critically, the incorporated external entrainment induced a modulatory effect from the auditory cortex to the BNST-NAc circuit, activating the antidepressant response and highlighting the causal role of physiological entrainment in enhancing the antidepressant response. Our study explores the pivotal role of the auditory cortex and proposes a neural oscillation triple time-locking model, emphasizing the capacity of the auditory cortex to access the BNST-NAc circuit.
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Cronobacter sakazakii is an opportunistic pathogen known for causing severe diseases. Mild heat treatment is commonly used in food processing, however, the pathogenic characteristics and underlying mechanisms of Cronobacter sakazakii strains remain poorly understood. In this study, we found that mild heat stress (MHS) at 52 °C can induce several deleterious effects in Cronobacter sakazakii, including damage to the cell wall, genomic DNA breakage, and misfolding of cytoplasmic proteins. These conditions lead to a decreased survival ability under acid, desiccation, and osmotic stress; a reduction in biofilm formation; and diminished motility. Notably, surviving C. sakazakii cells retain their pathogenicity, causing significant intestinal damage in newborn mice. This damage is characterized by epithelial sloughing and disruption of the intestinal structure. Tandem mass tag (TMT)-based proteomics identified 736 proteins with differential abundance across C. sakazakii strains subjected to mild heat stress, highlighting adaptations in biofilm formation, motility, and stress tolerance. Key regulatory changes were observed in phospholipid metabolism and protein synthesis, which underpin this complex stress response. This data illustrates a sophisticated balance between environmental adaptability and pathogenic potential. The metabolic and pathogenic responses of C. sakazakii to mild heat stress are closely linked to its phospholipid metabolism and the production of secretory proteins, both crucial for its virulence and reliant on membrane transport. This complex interplay emphasizes the need to understand these mechanisms to develop effective control strategies.
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BACKGROUND: Evidence suggests a robust relationship between experiencing bullying victimization (BV) and engaging in murderous behaviors among adolescents. However, the potential mediating effect of impulsivity on the relationship between BV and murderous behaviors in early adolescents remains underexplored. METHODS: A total of 5724 adolescents, with a mean age of 13.5 years, were enrolled from three middle schools in Anhui Province, China. Participants completed self-report questionnaires detailing their experiences with bullying, impulsiveness, and murderous behaviors. To assess the relationship between BV and murderous behaviors, multivariate logistic regression and Poisson regression analyses were conducted. Mediation analysis was performed using structural equation modeling. RESULTS: After controlling for confounding factors, a positive association was found between experiencing BV and engaging in murderous behaviors (p < 0.05). Mediation analysis revealed a significant indirect effect of BV on the occurrence of murderous behaviors through impulsivity (indirect effect = 0.027, 95 % CI: 0.021, 0.033). BV appears to heighten levels of impulsivity, which in turn increases the likelihood of murderous behaviors. Additionally, sex-specific analysis indicated that impulsivity played a greater mediating role in the link between verbal and relational BV and murderous behaviors in females, while physical and cyber BV were more significant in males. CONCLUSIONS: Our findings underscore the necessity of early targeted interventions for adolescents experiencing BV and exhibiting high levels of impulsivity to mitigate their risk of engaging in murderous behaviors.
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OBJECTIVE: A robotic system was recently introduced to improve prosthetic alignment during total knee arthroplasty (TKA). The purpose of this multicenter, prospective, randomized controlled trial (RCT) was to determine whether robotic-arm-assisted TKA improves clinical and radiological outcomes when compared to conventional TKA. METHODS: One hundred and thirty patients who underwent primary TKA were enrolled in this prospective, randomized controlled trial, which was conducted at three hospitals. Five patients were lost to follow-up 6 weeks after surgery. Therefore, 125 participants (63 in the intervention group and 62 in the control group) remained in the final analysis. The primary outcome was the rate at which the mechanical axis of the femur deviated by less than 3° from the mechanical axis of the tibia. This was evaluated by full-length weight-bearing X-rays of the lower limb 6 weeks postoperatively. Secondary outcomes included operation times, 6-week postoperative functional outcomes evaluated by the American Knee Society score (KSS) and the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), short form-36 (SF-36) health survey results, and the occurrence of adverse events (AEs) and serious adverse events (SAEs). RESULTS: At 6 weeks postoperatively, we found that the rate of radiographic inliers was significantly higher in the intervention group (78.7% vs 51.6%; p = 0.00; 95% confidence interval, 10.9% to 43.2%). The operation was significantly longer in the intervention group than in the control group (119.5 vs 85.0 min; p = 0.00). There were no significant differences in the 6-week postoperative functional outcomes, SF-36, AEs, and SAEs between the two groups. There were no AEs or SAEs that were determined to be "positively related" to the robotic system. CONCLUSION: Robotic-arm-assisted TKA is safe and effective, as demonstrated in this trial.
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AIMS: Androgen receptor inhibitors (ARIs) have become an effective treatment for advanced prostate cancer (PC). However, it is unknown which ARI is the most helpful and safe for men with advanced PC. Our aim is to help physicians make clinical decisions and provide medication guidelines for patients with advanced PC to avoid potential risks when using ARIs for treatment. METHODS: We systematically searched the following databases: PubMed, Embase and Cochrane Library, with a literature publication deadline of February 2023. The primary efficacy outcomes were 18-month overall survival (OS), treatment-emergent adverse events (TEAEs), hypertension and fatigue. The network meta-analysis (NMA) was performed by Stata 15.1, and Revman 5.3 was used to assess the included studies' risk of bias. RESULTS: The analysis included 26 trials with 26 263 people. The surface under the cumulative ranking curve (SUCRA) concluded that enzalutamide (86.8%) showed the best effect in prolonging the OS of patients. Flutamide led to the highest risk of TEAEs (29.9%) and AEs leading to discontinuation (12.8%). Apalutamide (13.4%) led to the highest risk of grade ≥3 TEAEs. Enzalutamide had the highest risk of hypertension (0.2%), grade ≥3 hypertension (4.5%) and fatigue (5.2%). CONCLUSIONS: This NMA indicates there is no one ARI to reach both the most effective and safe therapy aims for treating advanced PC and that there is a compromise between the efficacy and safety of ARIs in the treatment of advanced PC. Physicians should weigh the risks to safety against the anticipated benefits when prescribing these drugs to patients with PC.
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Background and Importance: Postoperative cough is a common complication of general anesthesia after bronchoscopy. The aim of the present study was to determine the safety profile and efficacy of piriform recess instillation with lidocaine in reducing the incidence of coughing. Objective: To what extent could piriform recess instillation with lidocaine decrease the incidence of cough at 10min after extubation? Outcome Measures and Analysis: Eighty-eight consecutive patients were equally randomized to a lidocaine group receiving piriform recess instillation with 2mL 2% lidocaine, and a normal saline group receiving piriform recess instillation with 2mL saline. The primary outcome was the incidence of cough after extubation, and the secondary outcomes were throat score at 10 min and 6 h after extubation assessed by the numerical rating scale, cough severity at 10 min and 6 h after extubation assessed by the Visual Analog Scale (VAS), 24 h 40-item Quality of Recovery Score (QoR-40), and subject-rated satisfaction score on a VAS. Main Results: Compared with saline group, the incidence of cough in lidocaine group was significantly lower (63.6% vs 86.4%, P=0.014). The sore throat score at 10 min after extubation was significantly lower (0[0,0] vs 1[0,2], P<0.001). The subject-rated overall anesthesia satisfaction score was significantly higher (84.8[±6.2] vs 76.6[±8.6], P<0.001). The severity of cough at 10 min after extubation was significantly lower (Mild: 36.4% vs 11.4%, P=0.006; Severe: 9.1% vs 43.2%, P<0.001). There was no significant difference in the sore throat score at 6 h after extubation, severity of cough at 6 h after extubation, or QoR-40 at 24 h after extubation between the two groups. Conclusion: Piriform recess instillation with lidocaine before bronchoscopy is a simple and effective method for reducing early cough intensity and alleviating early sore throat. At 6 hours, there were no differences observed between the groups. Clinical Trial Registration: Chinese Clinical Trial Registry (identifier: ChiCTR2200067087).
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Anestesia General , Broncoscopía , Tos , Lidocaína , Humanos , Lidocaína/administración & dosificación , Tos/prevención & control , Masculino , Femenino , Persona de Mediana Edad , Anestesia General/efectos adversos , Adulto , Anestésicos Locales/administración & dosificación , Anciano , Instilación de Medicamentos , Método Doble CiegoRESUMEN
Metallo-supramolecular cages have garnered tremendous attention for their diverse yet molecular-level precision structures. However, the physical properties of these supramolecular ensembles, which are of potential significance in molecular electronics, remain largely unexplored. We herein constructed a series of octahedral metallo-cages and cage-fullerene complexes with notably enhanced structural stability. As such, we could systematically evaluate the electrical conductivity of these ensembles at both the single-molecule level and aggregated bulk state (as well-defined films). Our findings reveal that counteranions and fullerene guests play a pivotal role in determining the electrical conductivity of the aggregated state, while such effects are less significant for single-molecule conductance. Both the counteranions and fullerenes effectively tune the electronic structures and packing density of metallo-supramolecular assemblies, and facilitate efficient charge transfer between the cage hosts and fullerenes, resulting in a notable one order of magnitude increase in the electrical conductivity of the aggregated state.
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To manage the interactions between wax and hydrate formation, a comprehensive understanding of the system's thermodynamics and flow characteristics is essential. Wax and hydrates coexist under low-temperature and high-pressure conditions, mutually influencing each other both thermodynamically and kinetically. This study focused on two main aspects: how wax affects the rate of hydrate formation in the oil-water system and how hydrate formation influences the thermodynamics of wax crystal precipitation. The presence of wax decreased the rate of hydrate formation, especially at higher wax contents. In systems with high wax content, over 70% of wax precipitated before hydrate formation, leading to less precipitation within the hydrate formation temperature range. With low water content, there were more nucleation sites for wax crystals in the oil phase, resulting in a greater difference in precipitation rates among different wax contents. For water content greater than 10%, the differences in precipitation rates were less significant, indicating a diminished effect of water content on wax crystal precipitation rates. Hydrates' hydrophilic nature had a limited impact on wax crystal nucleation and growth. Generally, wax crystals precipitate before hydrate formation, necessitating control measures for wax deposition during production processes.
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Multisite chronic pain (MCP) and site-specific chronic pain (SSCP) may be influenced by circulating inflammatory proteins, but the causal relationship remains unknown. To overcome this limitation, two-sample bidirectional Mendelian randomization (MR) analysis was used to analyse data for 91 circulating inflammatory proteins, MCP and SSCP encompassing headache, back pain, shoulder pain, hip pain, knee pain, stomach abdominal pain and facial pain. The primary MR method used was inverse variance weighting, sensitivity analyses included weighted median, MR pleiotropy residual sum and outlier and the Egger intercept method. Heterogeneity was also detected using Cochrane's Q test and leave-one-out analyses. Finally, a causal relationship between 29 circulating inflammatory proteins and chronic pain was identified. Among these proteins, 14 exhibited a protective effect, including MCP (T-cell surface glycoprotein cluster of differentiation 5), headache (4E-binding protein 1 [4EBP1], cluster of differentiation 40, cluster of differentiation 6 and C-X-C motif chemokine [CXCL] 11), back pain (leukaemia inhibitory factor), shoulder pain (fibroblast growth factor [FGF]-5 and interleukin [IL]-18R1), stomach abdominal pain (tumour necrosis factor [TNF]-α), hip pain (CXCL1, IL-20 and signalling lymphocytic activation molecule 1) and knee pain (IL-7 and TNF-ß). Additionally, 15 proteins were identified as risk factors for MCP and SSCP: MCP (colony-stimulating factor 1, human glial cell line-derived neurotrophic factor and IL-17C), headache (fms-related tyrosine kinase 3 ligand, IL-20 receptor subunit α [IL-20RA], neurotrophin-3 and tumour necrosis factor receptor superfamily member 9), facial pain (CXCL1), back pain (TNF), shoulder pain (IL-17C and matrix metalloproteinase-10), stomach abdominal pain (IL-20RA), hip pain (C-C motif chemokine 11/eotaxin-1 and tumour necrosis factor ligand superfamily member 12) and knee pain (4EBP1). Importantly, in the opposite direction, MCP and SSCP did not exhibit a significant causal impact on circulating inflammatory proteins. Our study identified potential causal influences of various circulating inflammatory proteins on MCP and SSCP and provided promising treatments for the clinical management of MCP and SSCP.
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Análisis de la Aleatorización Mendeliana , Humanos , Dolor Crónico/sangre , Dolor Crónico/genética , Inflamación/sangre , Inflamación/genética , Mediadores de Inflamación/sangreRESUMEN
BACKGROUND: Myopericytoma is a benign tumor that typically occurs within subcutaneous tissue and most often involves the distal extremities, followed by the proximal extremities, neck, thoracic vertebrae and oral cavity. Complete resection is often curative. Malignant myopericytoma is extremely rare and has a poor prognosis. Here, we report for the first time a case of malignant myopericytoma originating from the colon. CASE SUMMARY: A 69-year-old male was admitted to our hospital with right upper quadrant pain for five days. Imaging suggested a liver mass with hemorrhage. A malignant hepatic tumor was the initial diagnosis. Surgical resection was performed after a complete preoperative work up. Initial postoperative pathology suggested that the mass was a malignant myoblastoma unrelated to the liver. Four months after the first surgery, an enhanced computed tomography (CT) scan revealed a recurrence of the tumor. The diagnosis of malignant myopericytoma derived from the colon was confirmed on histopathological examination of the specimen from the second surgery. The patient did not return to the hospital regularly for surveillance. The first postoperative abdominal CT examination six months after the second surgery demonstrated multiple liver metastases. Survival time between the diagnosis of the tumor to death was approximately one year. CONCLUSION: Malignant myopericytoma is a rare cancer. Preoperative diagnosis may be difficult. Due to a lack of treatment options, prognosis is poor.
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BACKGROUND: Molecularly targeted therapies have recently become a hotspot in the treatment of LUAD, with ongoing efforts to identify new effective targets due to individual variability. Among these potential targets, the mitochondrial transcription elongation factor (TEFM) stands out as a crucial molecule involved in mitochondrial synthetic transcriptional processing. Dysregulation of TEFM has been implicated in the development of various diseases; however, its specific role in LUAD remains unclear. METHODS: We conducted a comprehensive analysis of TEFM expression in LUAD, leveraging data from the TCGA database. Subsequently, we validated these findings using clinical specimens obtained from the First Affiliated Hospital of Soochow University, employing western blotting and qRT-PCR techniques. Further experimental validation was performed through the transfection of cells with TEFM overexpression, knockdown, and knockout lentiviruses. The effects of TEFM on LUAD were evaluated both in vitro and in vivo using a range of assays, including CCK-8, colony formation, EdU incorporation, Transwell migration, Tunel assay, flow cytometry, JC-1 staining, and xenograft tumour models. RESULTS: Our investigation uncovered that TEFM exhibited elevated expression levels in LUAD and exhibited co-localization with mitochondria. Overexpression of TEFM facilitated malignant processes in LUAD cells, whereas its silencing notably curbed these behaviors and induced mitochondrial depolarization, along with ROS production, culminating in apoptosis. Moreover, the absence of TEFM substantially influenced the expression of mitochondrial transcripts and respiratory chain complexes. Results from nude mouse xenograft tumors further validated that inhibiting TEFM expression markedly hindered tumor growth. CONCLUSION: TEFM promotes LUAD malignant progression through the EMT pathway and determines apoptosis by affecting the expression of mitochondrial transcripts and respiratory chain complexes, providing a new therapeutic direction for LUAD-targeted therapy.
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Apoptosis , Mitocondrias , Factores de Elongación Transcripcional , Humanos , Animales , Mitocondrias/metabolismo , Línea Celular Tumoral , Factores de Elongación Transcripcional/metabolismo , Factores de Elongación Transcripcional/genética , Apoptosis/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica , Proliferación Celular , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/terapia , Movimiento Celular , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones , Especies Reactivas de Oxígeno/metabolismo , Terapia Molecular Dirigida , Femenino , MasculinoRESUMEN
Idiopathic pulmonary fibrosis (IPF) is believed to be associated with a notable disruption of cellular energy metabolism. By detecting the changes of energy metabolites in the serum of patients with pulmonary fibrosis, we aimed to investigate the diagnostic and prognostic value of energy metabolites in IPF, and further elucidated the mechanism of their involvement in pulmonary fibrosis. Through metabolomics research, it was discovered that the TCA cycle intermediates changed dramatically in IPF patients. In another validation cohort of 55 patients with IPF compared to 19 healthy controls, it was found that succinate, an intermediate product of TCA cycle, has diagnostic and prognostic value in IPF. The cut-off levels of serum succinate were 98.36 µM for distinguishing IPF from healthy controls (sensitivity, 83.64%; specificity, 63.16%; likelihood ratio, 2.27, respectively). Moreover, a high serum succinate level was independently associated with higher rates of disease progression (OR 13.087, 95%CI (2.819-60.761)) and mortality (HR 3.418, 95% CI (1.308-8.927)). In addition, accumulation of succinate and increased expression of the succinate receptor GPR91 were found in both IPF patients and BLM mouse models of pulmonary fibrosis. Reducing succinate accumulation in BLM mice alleviated pulmonary fibrosis and 21d mortality, while exogenous administration of succinate can aggravate pulmonary fibrosis in BLM mice. Furthermore, GPR91 deficiency protected against lung fibrosis caused by BLM. In vitro, succinate promoted the activation of lung fibroblasts by activating ERK pathway through GPR91. In summary, succinate is a promising biomarker for diagnosis and prognosis of IPF. The accumulation of succinate may promote fibroblast activation through GPR91 and pulmonary fibrosis.
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Fibrosis Pulmonar Idiopática , Receptores Acoplados a Proteínas G , Ácido Succínico , Ácido Succínico/metabolismo , Ácido Succínico/sangre , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Humanos , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Fibrosis Pulmonar Idiopática/mortalidad , Animales , Masculino , Ratones , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Modelos Animales de Enfermedad , Biomarcadores/sangre , Fibroblastos/metabolismo , Ciclo del Ácido CítricoRESUMEN
BACKGROUND: A rapid screening test for urinary tract infections (UTIs) in children is needed to avoid unnecessary cultures and provide prompt reports to make appropriate clinical decisions. We have evaluated for the first time the performance of the Sysmex UF-5000 flow cytometer as a screening tool for UTIs in children. METHODS: This study included 4445 pediatric patients, with urinary sediment and urine culture data collected from January 2020 to September 2023. The Sysmex UF-5000 analyzer was utilized to measure urine white blood cell (WBC) and bacteria (BACT), with the findings being compared to the culture results. RESULTS: At ≥ 104 colony-forming unit (CFU)/mL, 513 samples were culture-positive (400 samples presented 104-105 CFU/mL, and 113 demonstrated ≥ 105 CFU/mL bacterial growth). Optimal indicators for positive cultures were BACT counts of 92.2/µL (AUC: 0.944) and WBC counts of 40.8/µL (AUC:0.863). False negative rate were 0.9% when using a 7.8 bacteria/µL cut-off and avoiding unnecessary cultures in 28.1%. The UF-5000 has a higher consistency rate for Gram-negative (GN) bacteria (90.3%) than Gram-positive (GP) bacteria (86.8%). For samples with 105 CFU/mL, UF-5000's Bacteria -Information flags showed superior concordance for samples with 104-105 CFU/mL bacteria. CONCLUSIONS: Screening pediatric urine cultures with the UF-5000 showed potential application value in identifying negative cultures and significant bacterial growth, although performance may vary depending on the study population. Furthermore, detecting Gram typing aids in guiding early clinical empirical medication, particularly for UTIs caused by GN bacteria.
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Toma de Decisiones Clínicas , Infecciones Urinarias , Humanos , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/microbiología , Niño , Preescolar , Femenino , Masculino , Lactante , Recuento de Leucocitos , Citometría de Flujo/métodos , Adolescente , Urinálisis/métodos , Urinálisis/instrumentación , Tamizaje Masivo/métodos , Recién NacidoRESUMEN
Selumetinib is an oral, effective, and selective tyrosine kinase inhibitor targeting mitogen-activated protein kinase 1 and 2 (MEK1/2), which is clinically active in multiple tumor types, such as neurofibromatosis type 1 (NF1), melanoma, gliomas and non-small cell lung cancer (NSCLC). The purpose of this article was to assess the effects of selumetinib on the activities of twelve human UDP-glucosyltransferases (UGTs) including UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15, and 2B17, and its potential for inducing clinical drug-drug interactions (DDIs). The results demonstrated that selumetinib potently inhibited the activity of UGT2B7 through the mechanism of mixed inhibition with the inhibition constant value of 5.79 ± 0.65 µM. Furthermore, the plasma concentration of UGT2B7 substrate as the co-administered drug was predicted to be increased by at least 84 % when patients took selumetinib 75 mg twice daily, suggesting a high potential to induce clinical DDIs. Selumetinib exhibited weak inhibitory effects on other human UGTs and was unlikely to trigger off UGTs-mediated DDIs except for UGT2B7. Therefore, the combination of selumetinib with the substrate drug of UGT2B7 requires additional attention to avoid adverse events in clinical treatment.
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Bencimidazoles , Interacciones Farmacológicas , Glucuronosiltransferasa , Humanos , Glucuronosiltransferasa/metabolismo , Glucuronosiltransferasa/antagonistas & inhibidores , Bencimidazoles/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Microsomas Hepáticos/efectos de los fármacosRESUMEN
Osteopontin (Opn) depletion can improve septic outcomes, but the underlying mechanism remains unknown. In this study, we demonstrated that non-haematopoietic but not haematopoietic Opn depletion improved septic outcomes. Compared to wild-type (WT) mice, co-housed Opn-/- mice displayed enhanced production of antibacterial peptides (AMPs), decreased bacterial loads, and a distinct bacterial composition of gut microbiota. Fecal microbiota transplantation (FMT) and OPN neutralization assay showed that Opn depletion could reduce the bacterial loads and improve septic inflammation. By employing an intestinal organoid culture system, we proved that OPN neutralization in WT organoids could inactivate AKT and decrease FOXO3a phosphorylation, resulting in enhanced AMP production, whereas OPN treatment in OPN deficient organoids could activate AKT and increase FOXO3a phosphorylation, leading to reduced AMP production. Our findings identified OPN as a novel regulatory factor of AMP production to modulate bacterial loads and composition of gut microbiota, in turn affecting sepsis outcomes.
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BACKGROUND: Pleural solitary fibrous tumors (pSFTs) are rare mesenchymal pleural tumors with rich vascularity. Surgical resection is the cornerstone of pSFTs treatment, requiring careful preoperative imaging to delineate lesion extent and vascular supply including contrast-enhanced computed tomography and other examinations depending on its size and characteristics. CASE PRESENTATION: The patient was a 34-year-old female with a mass measuring approximately 67 × 42 × 65 mm in the left posterior mediastinum. Intraoperatively, the mass demonstrated rich vascularity. Two veins originating from the abdominal cavity entered the lower pole, one converged from the superior pole, draining into the brachiocephalic vein. Additionally, two arteries arose directly from the descending aorta, while several veins drained into the intercostal veins. In response to unexpected intraoperative vascular findings, vascular clips and silk threads were used to ligate them. Subsequently, the tumor was successfully dissected, with approximately 600 ml of blood loss recorded during the 4-hour surgery. The patient exhibited a satisfactory postoperative recovery, and follow-up spanning over six months revealed no indications of recurrence or metastasis. CONCLUSIONS: We firstly present a case of successful resection of a pSFT in a 34-year-old woman with a distinct feeding vessel arising from the descending aorta and describe the related surgical procedures. This case highlights preoperative evaluation of mass vascularity based on contrast-enhanced computed tomography. When blood supply is challenging to clarify, angiography can offer additional details, especially for giant pSFTs. Despite this, thorough intraoperative exploration remains essential to detect unexpected vessels. Appropriate interventions should be customized based on the vascular origins and the surrounding anatomical structures.
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Aorta Torácica , Humanos , Femenino , Adulto , Aorta Torácica/cirugía , Aorta Torácica/diagnóstico por imagen , Tumor Fibroso Solitario Pleural/cirugía , Tumor Fibroso Solitario Pleural/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Death-associated protein-1 (DAP-1) plays a crucial role in cell growth, migration, autophagy, and apoptosis in mammals. However, its function in insects remains unclear. In the present study, we cloned and identified Nilaparvata lugens DAP-1 (NlDAP-1). NlDAP-1 was expressed during all developmental stages and in all tissues of N. lugens, being particularly higher in the ovaries of female adults. RNAi with double-stranded NlDAP-1 RNA significantly inhibited the expression of NlDAP-1, leading to premature death (dying seven days earlier), delayed ovarian development, and fewer offspring (76.7% reduction in eggs with 77.4% reduction in egg hatching rate). Additionally, an immunofluorescence experiment showed that NlDAP-1 was highly expressed when yeast-like symbionts (YLSs) entered N. lugens oocytes, and inhibiting the expression of NlDAP-1 disturbed the process; the RNAi of NlDAP-1 caused a 34.9% reduction in the YLSs that entered oocytes. These results indicate that NlDAP-1 plays a crucial role in the reproductive development of N. lugens and the transovarial transmission of its YLSs.