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1.
Parkinsonism Relat Disord ; 128: 107122, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39241506

RESUMEN

INTRODUCTION: Past studies suggested that Parkinson's disease (PD) patients who engage in physical activity (PA) after diagnosis have slower motor progression. Here, we examine the influence of lifetime PA prior to PD onset on motor, cognitive, and overall functional decline among PD patients. METHODS: For 495 participants in the Parkinson's Environment and Gene (PEG) studies, we collected PA-related measures through interviews and quantified these using metabolic equivalents (MET) scores. PD progression was defined as time to a Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) conversion to ≥ 35 points, Hoehn and Yahr (H&Y) ≥ 3, and a 4-point decline in Mini-Mental State Examination (MMSE). We used Cox frailty models to estimate hazard ratios and inverse probability weights to account for heterogeneity by enrollment wave and censoring. RESULTS: For PD patients reporting the highest lifetime strenuous MET-h/wk (highest quartile), we estimated a lower HR for time-to-UPDRS-III-conversion (Q4 vs. Q1: HR = 0.56, 95 % CI = [0.36, 0.87]). Additionally, having engaged in any competitive sport also reduced the risk of reaching a UPDRS-III ≥ 35 points (low vs. none: HR = 0.61, 95 % CI = [0.44, 0.86]; high vs. none: HR = 0.63; 95 % CI = [0.44,0.86]); high levels of sports activities also affected progression on the H&Y scale (high vs. none: HR = 0.73; 95 % CI = [0.46,1.00]). Lifetime PA measures did not affect time-to-MMSE decline. CONCLUSION: Our study suggests that PD patients who engaged in higher levels of lifetime strenuous PA and competitive sports prior to PD diagnosis experience slower motor and overall functional decline, suggesting that lifetime PA may contribute to a physical reserve advantageous for PD patients.

2.
Asian J Psychiatr ; 101: 104205, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39243662

RESUMEN

Mental disorders are becoming increasingly prevalent worldwide, and accurate incidence forecasting is crucial for effective mental health strategies. This study developed a long short-term memory (LSTM)-based recurrent neural network model to predict schizophrenia in inpatients in Taiwan. Data was collected on individuals aged over 20 years and diagnosed with schizophrenia between 1998 and 2015 from the National Health Insurance Research Database (NHIRD). The study compared six models, including LSTM, exponential smoothing, autoregressive integrated moving average, particle swarm optimization (PSO), PSO-based support vector regression, and deep neural network models, in terms of their predictive performance. The results showed that the LSTM model had the best accuracy, with the lowest mean absolute percentage error (2.34), root mean square error (157.42), and mean average error (154,831.70). This finding highlights the reliability of the LSTM model for forecasting mental disorder incidence. The study's findings provide valuable insights that can help government administrators devise clinical strategies for schizophrenia, and policymakers can use these predictions to formulate healthcare education and financial planning initiatives, fostering support networks for patients, caregivers, and the public.

3.
J Thorac Oncol ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39243945

RESUMEN

INTRODUCTION: The primary analysis (median follow-up 34.9 months across all arms) of the phase 3 POSEIDON study demonstrated a statistically significant overall survival (OS) improvement with first-line tremelimumab plus durvalumab and chemotherapy (T+D+CT) versus CT in patients with EGFR/ALK-wild-type metastatic NSCLC (mNSCLC). D+CT showed a trend for OS improvement versus CT that did not reach statistical significance. This paper reports prespecified OS analyses after longer-term follow-up (median >5 years). METHODS: 1013 patients were randomized (1:1:1) to T+D+CT, D+CT, or CT, stratified by tumor cell (TC) PD-L1 expression (≥50% vs <50%), disease stage (IVA vs IVB), and histology (squamous vs nonsquamous). Serious adverse events were collected during follow-up. RESULTS: After median follow-up of 63.4 months across all arms, T+D+CT showed sustained OS benefit versus CT (hazard ratio [HR] 0.76, 95% CI: 0.64-0.89; 5-year OS: 15.7% vs 6.8%). OS improvement with D+CT versus CT (HR 0.84, 95% CI: 0.72-1.00; 5-year OS: 13.0%) was consistent with the primary analysis. OS benefit with T+D+CT versus CT remained more pronounced in nonsquamous (HR 0.69, 95% CI: 0.56-0.85) versus squamous (HR 0.85, 95% CI: 0.65-1.10) mNSCLC. OS benefit with T+D+CT versus CT was still evident regardless of PD-L1 expression, including patients with PD-L1 TC <1%, and remained evident in STK11-mutant (nonsquamous), KEAP1-mutant, and KRAS-mutant (nonsquamous) mNSCLC. No new safety signals were identified. CONCLUSIONS: After median follow-up of >5 years, T+D+CT showed durable long-term OS benefit versus CT, supporting its use as first-line treatment in mNSCLC, including in patient subgroups with harder-to-treat disease.

4.
J Cancer ; 15(16): 5462-5476, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247603

RESUMEN

Breast cancer (BC) is a prevalent malignancy globally. Autophagy plays a pivotal role in all stages of this disease, including development, metastasis, and onset. Therefore, it is envisaged that targeting cell autophagy through appropriate tactics would evolve into a novel breast cancer prevention and therapy strategy. A multitude of chemotherapeutic medications can stimulate autophagy in tumor cells. It has led to divergent opinions on the function of autophagy in cancer treatment, as both stimulating and blocking autophagy can improve the effectiveness of anticancer medications. Consequently, the decision of whether to stimulate or inhibit autophagy during breast cancer treatment has become crucial. Understanding the distinctive mechanisms of autophagy in BC and its significance in medication therapy might facilitate the creation of targeted treatment plans based on the roles particular to autophagy. This review summarizes recent studies on the autophagy mechanism in breast cancer and provides insights into autophagy-based BC therapeutic techniques, giving fresh avenues for future BC treatment.

5.
Clinics (Sao Paulo) ; 79: 100478, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39226870

RESUMEN

BACKGROUND: Lower limb coronal alignment was thought to be a predictive factor for Unicompartmental Knee Arthroplasty (UKA) result. The tibial bony resection and implant position lead to joint line change postoperatively. Analysis was done to find out the correlation between these factors. METHODS: From 2019 to 2021, 90 medial Oxford UKA were implanted by a single surgeon. Hip Knee Ankle Angle (HKAA), Lateral Distal Femoral Angle (LDFA), Medial Proximal Tibial Angle (MPTA), and intraoperative bony resection thickness were measured. The medial joint line change was calculated. The correlation between joint line change and alignment change was evaluated. RESULTS: The mean tibial resection thickness was 4.3 mm. The mean tibial joint line was elevated by 2.3 mm, while the mean femoral joint line proximalized by 0.8 mm. HKAA changed from 8.4° varus preoperatively to 3.6° varus postoperatively. LDFA changed from 89.0° to 86.7°. MPTA changed from 85.6° to 86.6°. Preoperative HKAA showed a strong correlation with postoperative HKAA (p < 0.001), and preoperative MPTA showed a positive correlation with postoperative HKAA (p < 0.001). While preoperative LDFA had a negative correlation with postoperative HKAA (p < 0.001). The femoral joint line change and LDFA change had a significant correlation with HKAA change (p < 0.05). CONCLUSION: The change of joint line had no correlation with postoperative HKAA in Oxford UKA. Preoperative HKAA strongly correlated with postoperative HKAA; while preoperative smaller LDFA and larger MPTA had a moderate correlation with postoperative HKAA. The femoral joint line change and LDFA change had a weak to moderate correlation with HKAA change.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Articulación de la Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Articulación de la Rodilla/cirugía , Tibia/cirugía , Estudios Retrospectivos , Fémur/cirugía , Prótesis de la Rodilla , Periodo Posoperatorio , Resultado del Tratamiento , Anciano de 80 o más Años , Osteoartritis de la Rodilla/cirugía
6.
Small ; : e2405495, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235359

RESUMEN

Benefiting from high volumetric capacity, environmental friendliness, and high safety, aluminum-ion batteries (AIBs) are considered to be promising battery system among emerging electrochemical energy storage technologies. As an important component of AIBs, the cathode material is crucial to decide the energy density and cycle life of AIBs. However, single-component cathode materials are unable to achieve a balance between cycling stability and rate performance. In recent years, research on heterostructure cathode materials has gained significant attention in AIBs. By harnessing the synergistic effects of heterostructure, the shortcomings of individual materials can be overcome, contributing to improved conductivity and structural stability. This review offers a detailed insight into the Al-storage mechanism of heterostructure cathodes, and provides an overview of the current research progresses on heterostructure cathode materials for AIBs. Starting from the relationship between the microstructure and electrochemical performance of heterostructure materials, the different structure design strategies are elaborated. Besides, the challenges faced by heterostructure are summarized, and their potential impact on the future of the energy storage industry is anticipated. This review provides the guidelines for the future research of heterostructure as cathode materials for AIBs.

7.
PLoS One ; 19(9): e0309941, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39241021

RESUMEN

INTRODUCTION: Visceral metastasis is an important predictor for poor outcomes in prostate cancer, however, the prognostic significance surrounding the specific sites of visceral metastasis remains unclear. The aim of this study was to evaluate the impact of different visceral metastatic sites on survival in patients with prostate cancer. METHODS: We identified patients with metastatic prostate cancer between January 1, 2010 and December 31, 2023 using the TriNetX database. Patients were divided into 4 cohorts according to their specific metastatic sites: lung metastases, brain metastases, liver metastases, and bone metastases. Survival analysis was calculated using the Kaplan-Meier method and Cox regression models. RESULTS: In total, 59,875 patients diagnosed with metastatic prostate cancer were identified, with 39,495 (65.2%) having bone metastases, 7,573 (12.5%) lung metastases, 5,240 (8.7%) brain metastases, and 7,567 (12.5%) liver metastases. The median overall survival was 44.4 months for patients with bone metastases, 31.9 months for lung metastases, 9.6 months for brain metastases, and 10 months for liver metastases. Lung metastases were associated with an improved survival when compared with liver and brain metastases. For patients with two visceral metastatic sites or concomitant bone metastases, liver metastases were related to worse outcomes. Asian patients experienced better OS than Caucasian and African American patients in visceral metastatic prostate cancer. CONCLUSION: Patients with lung metastases experienced better survival outcomes in prostate cancer with only one visceral metastatic site. Liver metastases were associated with worse outcomes when there were two visceral metastatic sites combined or concomitant bone metastases. Asian patients displayed improved survival rates when compared with both Caucasian and African American patients in visceral metastatic prostate cancer.


Asunto(s)
Neoplasias Óseas , Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/mortalidad , Anciano , Neoplasias Óseas/secundario , Neoplasias Óseas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/mortalidad , Persona de Mediana Edad , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Pronóstico , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/mortalidad , Estimación de Kaplan-Meier , Metástasis de la Neoplasia , Anciano de 80 o más Años , Modelos de Riesgos Proporcionales
8.
Chin J Traumatol ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39227204

RESUMEN

Traumatic main bronchus rupture is a relatively rare injury in thoracic trauma, which is extremely critical, with a mortality rate as high as 70% - 80%. The complete rupture and displacement of the traumatic cervical trachea can lead to asphyxia, hypoxia, and cardiac arrest, even death of the patient in a short time. We performed emergency surgery with the support of extracorporeal membrane oxygenation for a case of traumatic cervical tracheal trunk complete rupture and displacement combined with cardiac arrest and achieved a successful rescue. We summarized our experience and found that timely surgical reconstruction of the airway is the key to increasing the traumatic main bronchus rupture survival of patients.

10.
Heliyon ; 10(17): e36928, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39281513

RESUMEN

The solution to the economic dispatch (ED) problem for power systems allows the power sector to reduce operating costs. However, the ED problem is a complex nonlinear and nonconvex optimization problem whose solution requires powerful algorithms. We propose a new version of the Marine Predator Algorithm (MPA), called IMPA, for solving complex ED problems. The algorithm introduces an asymmetric information exchange (AIE) mechanism, which not only accelerates to escape of local optima but also enriches the diversity of search. In this work, 12 benchmark functions were used to test the performance of the proposed algorithm IMPA. Then, the IMPA was used to solve the ED engineering problem of power system containing of 6, 13, 40, and complex 140 units. The minimum and average costs searched by IMPA are 1657962.7265$/h and 1657962.7265$/h, and they are much lower than the results of the MPA and NMPA, which means that our proposed improved IMPA improves the performance of MPA for solving the economic dispatch problem of large-scale power systems. The results show that the solutions obtained by IMPA are more competitive than those of MPA and NMPA, which provides an additional solution for cost reduction of the power system.

11.
Artículo en Inglés | MEDLINE | ID: mdl-39231053

RESUMEN

Deep multiview clustering provides an efficient way to analyze the data consisting of multiple modalities and features. Recently, the autoencoder (AE)-based deep multiview clustering algorithms have attracted intensive attention by virtue of their rewarding capabilities of extracting inherent features. Nevertheless, most existing methods are still confronted by several problems. First, the multiview data usually contains abundant cross-view information, thus parallel performing an individual AE for each view and directly combining the extracted latent together can hardly construct an informative view-consensus feature space for clustering. Second, the intrinsic local structures of multiview data are complicated, hence simply embedding a preset graph constraint into multiview clustering models cannot guarantee expected performance. Third, current methods commonly utilize the Kullback-Leibler (KL) divergence as clustering loss and accordingly may yield appalling clusters that lack discriminate characters. To solve these issues, in this article we propose two new AE-based deep multiview clustering algorithms named AE-based deep multiview clustering model incorporating graph embedding (AG-DMC) and deep discriminative multiview clustering algorithm with adaptive graph constraint (ADG-DMC). In AG-DMC, a novel cross-view representation learning model is established delicately by performing decoding processes based on the cascaded view-specific latent to learn sound view-consensus features for inspiring clustering results. In addition, an entropy-regularized adaptive graph constraint is imposed on the obtained soft assignments of data to precisely preserve potential local structures. Furthermore, in the improved model ADG-DMC, the adversarial learning mechanism is adopted as clustering loss to strengthen the discrimination of different clusters for better performance. In the comprehensive experiments carried out on eight real-world datasets, the proposed algorithms have achieved superior performance in the comparison with other advanced multiview clustering algorithms.

12.
Genet Sel Evol ; 56(1): 60, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227836

RESUMEN

BACKGROUND: Accurate breed identification is essential for the conservation and sustainable use of indigenous farm animal genetic resources. In this study, we evaluated the phylogenetic relationships and genomic breed compositions of 13 sheep breeds using SNP and InDel data from whole genome sequencing. The breeds included 11 Chinese indigenous and 2 foreign commercial breeds. We compared different strategies for breed identification with respect to different marker types, i.e. SNPs, InDels, and a combination of SNPs and InDels (named SIs), different breed-informative marker detection methods, and different machine learning classification methods. RESULTS: Using WGS-based SNPs and InDels, we revealed the phylogenetic relationships between 11 Chinese indigenous and two foreign sheep breeds and quantified their purities through estimated genomic breed compositions. We found that the optimal strategy for identifying these breeds was the combination of DFI_union for breed-informative marker detection, which integrated the methods of Delta, Pairwise Wright's FST, and Informativeness for Assignment (namely DFI) by merging the breed-informative markers derived from the three methods, and KSR for breed assignment, which integrated the methods of K-Nearest Neighbor, Support Vector Machine, and Random Forest (namely KSR) by intersecting their results. Using SI markers improved the identification accuracy compared to using SNPs or InDels alone. We achieved accuracies over 97.5% when using at least the 1000 most breed-informative (MBI) SI markers and even 100% when using 5000 SI markers. CONCLUSIONS: Our results provide not only an important foundation for conservation of these Chinese local sheep breeds, but also general approaches for breed identification of indigenous farm animal breeds.


Asunto(s)
Cruzamiento , Mutación INDEL , Polimorfismo de Nucleótido Simple , Ovinos , Animales , Cruzamiento/métodos , China , Genética de Población/métodos , Filogenia , Ovinos/genética , Secuenciación Completa del Genoma/métodos , Secuenciación Completa del Genoma/veterinaria
13.
Anal Chem ; 96(37): 14867-14876, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39238447

RESUMEN

Mass spectrometry (MS) using an electron multiplier for intact protein analysis remains limited. Because of the massive size and complex structure of proteins, the slow flight speed of their ions results in few secondary electrons and thus low detection sensitivity and poor spectral resolution. Thus, we present a compact ion trap-mass spectrometry approach to directly detect ion packets and obtain the high-resolution molecular signature of proteins. The disturbances causing deviations of ion motion and mass conversion have been clarified in advance. The radio frequency waveform used to manipulate ions is proposed to be a sequence of constant-frequency steps, interconnected by short time-outs, resulting in least dispersive distortion. Furthermore, more such constant-phase conjunctions are arranged in each step to compensate for fluctuations resulting from defects in the system and operation. In addition, two auxiliary pulses are generated in the right phase of each step to select ions of a specific secular state to detect one clean and sharp spectral line.This study demonstrates a top-down approach for the MS measurement of cytochrome C molecules, resulting in a spectral profile of the protein in its natural state at a resolution of 20 Da. Additionally, quick MS scans of other proteins were performed.


Asunto(s)
Citocromos c , Espectrometría de Masas , Citocromos c/análisis , Citocromos c/química , Espectrometría de Masas/métodos , Proteínas/análisis , Proteínas/química
14.
Materials (Basel) ; 17(17)2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39274624

RESUMEN

To fully exploit the advantages of steel, the welding connection of dissimilar steels has been developed. In this work, the metallographic microstructures, elemental distributions, and electrochemical corrosion properties of the Q235 and 304 welds under different bias arcs were investigated. The arc bias caused the Q235-side heat-affected zone to widen, the microstructure consisted of ferrite and pearlite, and the ratio varied with decreasing distance from the fusion line. Elemental scans show that Cr and Ni concentration gradients exist near the fusion line. The 304-stainless-steel-side heat-affected zone was mainly composed of austenite grains, and the fusion zone was narrower but prone to cracking. Electrochemical tests revealed that 304 stainless steel had the best corrosion resistance, while Q235 had the worst corrosion resistance, and that the welded joints with an arc bias toward the 304 side had the best corrosion resistance. The samples' the passivation film which formed via electrochemical polarization had limited stability, but the over-passivation potential could be used as a reference for corrosion resistance. Overall, the arc bias and weld material properties significantly affected the microstructure and corrosion resistance of the joints.

15.
Bioinformatics ; 40(9)2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39222004

RESUMEN

MOTIVATION: Natural language is poised to become a key medium for human-machine interactions in the era of large language models. In the field of biochemistry, tasks such as property prediction and molecule mining are critically important yet technically challenging. Bridging molecular expressions in natural language and chemical language can significantly enhance the interpretability and ease of these tasks. Moreover, it can integrate chemical knowledge from various sources, leading to a deeper understanding of molecules. RESULTS: Recognizing these advantages, we introduce the concept of conversational molecular design, a novel task that utilizes natural language to describe and edit target molecules. To better accomplish this task, we develop ChatMol, a knowledgeable and versatile generative pretrained model. This model is enhanced by incorporating experimental property information, molecular spatial knowledge, and the associations between natural and chemical languages. Several typical solutions including large language models (e.g. ChatGPT) are evaluated, proving the challenge of conversational molecular design and the effectiveness of our knowledge enhancement approach. Case observations and analysis offer insights and directions for further exploration of natural-language interaction in molecular discovery. AVAILABILITY AND IMPLEMENTATION: Codes and data are provided in https://github.com/Ellenzzn/ChatMol/tree/main.


Asunto(s)
Procesamiento de Lenguaje Natural , Humanos , Programas Informáticos , Biología Computacional/métodos
16.
J Neurooncol ; 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39276177

RESUMEN

INTRODUCTION: Spinal chondrosarcoma exhibits higher invasiveness and a worse prognosis compared to chondrosarcoma in the extremities. The prognosis and therapeutic plan vary greatly among different pathological subtypes of chondrosarcoma. This study aimed to analyze the differences in clinical characteristics, molecular features, therapeutic effects, and prognostic factors among the subtypes of chondrosarcoma in the spine. METHODS: A retrospective review was conducted on 205 patients with spinal chondrosarcoma. The clinical features and immunohistochemical (IHC) markers were compared among the pathological subtypes of chondrosarcoma grade 1, grade 2, grade 3, mesenchymal chondrosarcoma (MCS), dedifferentiated chondrosarcoma (DCS), and clear cell chondrosarcoma (CCCS). Chondrosarcoma grade 1/2/3 are collectively referred to as conventional chondrosarcoma (CCS) for multivariate survival analysis. Univariate and multivariate analyses were performed to investigate independent prognostic factors for overall survival (OS) and recurrence-free survival (RFS) in patients with spinal chondrosarcoma. Furthermore, independent prognostic factors for OS and RFS were identified in CCS and MCS. RESULTS: MCS patients were younger than the other subtypes. Patients with chondrosarcoma grade 1/2 had better OS than those with chondrosarcoma grade 3, MCS and DCS, while only chondrosarcoma grade 1 patients showed better RFS than chondrosarcoma grade 2/3, MCS and DCS patients. Ki-67 index was higher in chondrosarcoma grade 3, MCS and DCS than chondrosarcoma grade 1/2. The comparison of IHC markers further highlighted the overexpression of P53/MDM2 in MCS and DCS. Gross total resection, including en-bloc and piecemeal resection, significantly improved OS and RFS for CCS patients, while only en-bloc resection significantly improved the prognosis of MCS patients. Chemotherapy appeared to be important for the OS of MCS patients. CONCLUSION: P53/MDM2 pathway was upregulated in MCS and DCS compared to chondrosarcoma grade 1/2. Radical tumor resection is crucial for the treatment of spinal chondrosarcoma, while MCS patients require further comprehensive treatments perioperatively.

17.
Front Pharmacol ; 15: 1423175, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39253379

RESUMEN

Introduction: Deglycosylated azithromycin (Deg-AZM), a newly developed Class I drug with good therapeutic effects on slow transit constipation, is a small-molecule transgelin agonist that has been approved for clinical trials in 2024. The preclinical pharmacokinetic profile of Deg-AZM was investigated to support further development. Methods: A LC-MS/MS method was established and validated to detected the concentration of Deg-AZM in various biological samples. In vivo tests such as pharmacokinetic studies in rats and dogs, tissue distribution studies in rats, and extraction studies in rats were conducted to investigated the preclinical pharmacokinetic behaviors of Deg-AZM comprehensively. The plasma protein rate of Deg-AZM was determined by rapid equilibrium dialysis method in vitro. The metabolic stability and metabolite profile of Deg-AZM was assessed using pooled mice, rats, dogs, monkeys and humans microsomes in vitro. The PK profiles of Deg-AZM in human was predicted based on physiologically based pharmacokinetic (PBPK) models. Results: The plasma protein binding rates of Deg-AZM were lower in mice and rats, higher in dogs, and moderate in humans. The metabolic process of Deg-AZM was similar in rat and human liver microsomes. From Pharmacokinetic studies in rats and dogs, Deg-AZM was rapidly absorbed into the blood and then quickly eliminated. Plasma exposure of Deg-AZM was dose dependent with no accumulation after continuous gavage administration. In addition, there is no significant gender difference in the pharmacokinetic behavior of Deg-AZM. Deg-AZM was widely distributed in the tissues without obvious accumulation, and mainly excreted from the urinary excretion pathway. Furthermore, the pharmacokinetic profiles of Deg-AZM in humans showed dose dependency. Conclusion: The pharmacokinetic profiles of Deg-AZM was fully explored, these results could provide valuable information to support the first-in-human dosage prediction and phase I clinical design.

18.
Anal Chim Acta ; 1326: 343138, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39260916

RESUMEN

BACKGROUND: Sulfonamide (SA) residues in food of animal origin possess a potential threat to human health and environment. However, due to the polar and ionic characteristics and trace level of SAs and the complexity of food matrices, direct measurement of SAs in these samples is still very difficult. Development of efficient sample pretreatment method for sensitive and selective extraction of trace SAs is of great significance and urgently desired. Therefore, rational design and synthesizing advanced and selective extractants is quite important. RESULTS: In this work, a novel phenazine-based microporous organic network (MON) named TEPM-DP is reasonably synthesized and employed as a packing material for selective solid phase extraction (SPE) and sensitive determination of four typical SAs in milk samples. Phenazine-based monomer with aromatic and heteroaromatic ring and numerous N atoms is chosen to construct TEPM-DP adsorbent to provide π-π, hydrogen bonding, hydrophobic, and electrostatic extraction sites for SAs. The proposed method owns wide linear ranges, low limits of detection, high enrichment factors, and good precisions and recoveries for SAs in complex milk samples. The recoveries of SAs on TEPM-DP are much higher than those of commercial C18 and activated carbon. The extraction mechanisms are also elucidated via FT-IR, XPS, and comparative experiments. SIGNIFICANCE: This work reports the first example of design and synthesizing phenazine-based MON in SPE via a simple and rapid solvothermal method. The results reveal the great prospects of TEPM-DP for enriching polar and ionic SAs in complex samples and uncover the potency of phenazine-based MON in sample pretreatment, which will promote the development of MON.


Asunto(s)
Leche , Fenazinas , Extracción en Fase Sólida , Sulfonamidas , Fenazinas/química , Leche/química , Animales , Sulfonamidas/análisis , Sulfonamidas/aislamiento & purificación , Extracción en Fase Sólida/métodos , Porosidad , Límite de Detección , Adsorción , Contaminación de Alimentos/análisis
19.
Pediatr Neonatol ; 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39278795

RESUMEN

BACKGROUNDS: Ample evidence supports potential influence of age at menarche (AM) on adult height (AH), but multiple confounders may affect causal estimates. To address this issue, the Mendelian randomization (MR) analysis was used to explore the causal impacts of AM on AH. METHODS: Using data (n = 57,349) from the publicly accessible Taiwan Biobank and randomly splitting them into 2 equal-size subsets, we identified single nucleotide polymorphisms (SNPs) significantly associated with AM in the exploration subset and used these SNPs as instrumental variables to estimate the effects of instruments on AH in the validation subset based on two stage least squares (2SLS) regression. In addition, three more summary statistics-based approaches, namely inverse variance weighted (IVW), MR-Egger, and weighted median (WM) analyses, were used to verify the findings. We also performed heterogeneity and sensitivity analyses to evaluate the robustness of the results. RESULTS: We identified 4 leading SNPs associated with AM at the genome-wide significant level, whereas rs9409082 may exert some pleiotropic effects on AH. After eliminating rs9409082, the 2SLS analysis indicated that one year delay in genetically determined AM predicted 1.5 cm height gain in adulthood (ß = 1.508, 95% confidence interval [0.852, 2.163]). The causal relationship was also supported by WM (ß = 1.183, [0.329, 2.038]) and IVW (ß = 1.493, [0.523, 2.463]) methods. CONCLUSIONS: Evidence from the present MR study supports a causal relationship between later AM and taller AH.

20.
World J Cardiol ; 16(8): 484-490, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39221188

RESUMEN

BACKGROUND: With the development of percutaneous coronary intervention (PCI), the number of interventional procedures without implantation, such as bioresorbable stents (BRS) and drug-coated balloons, has increased annually. Metal drug-eluting stent unloading is one of the most common clinical complications. Comparatively, BRS detachment is more concealed and harmful, but has yet to be reported in clinical research. In this study, we report a case of BRS unloading and successful rescue. CASE SUMMARY: This is a case of a 59-year-old male with the following medical history: "Type 2 diabetes mellitus" for 2 years, maintained with metformin extended-release tablets, 1 g PO BID; "hypertension" for 20 years, with long-term use of metoprolol sustained-release tablets, 47.5 mg PO QD; "hyperlipidemia" for 20 years, without regular medication. He was admitted to the emergency department of our hospital due to intermittent chest pain lasting 18 hours, on February 20, 2022 at 15: 35. Electrocardiogram results showed sinus rhythm, ST-segment elevation in leads I and avL, and poor R-wave progression in leads V1-3. High-sensitivity troponin I level was 4.59 ng/mL, indicating an acute high lateral wall myocardial infarction. The patient's family requested treatment with BRS, without implantation. During PCI, the BRS became unloaded but was successfully rescued. The patient was followed up for 2 years; he had no episodes of angina pectoris and was in generally good condition. CONCLUSION: We describe a case of a 59-year-old male experienced BRS unloading and successful rescue. By analyzing images, the causes of BRS unloading and the treatment plan are discussed to provide insights for BRS release operations. We discuss preventive measures for BRS unloading.

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