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1.
J Hazard Mater ; 443(Pt B): 130369, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36444065

RESUMO

Pharmaceuticals and personal care products (PPCPs) are commonly seen emerging organic contaminants in aquatic environments. The transects for the occurrence and distribution of 24 PPCPs along the middle and lower reaches of the Yellow River (Henan section) were investigated in this study. All 24 targeted compounds were detected in surface water, with concentrations in the range from not detected (ND) to 527.4 ng/L. Among these PPCPs, caffeine is found to have the highest concentration and its detection frequency is 100%. The total PPCP concentration ranged from 136 ng/L to 916 ng/L (median, 319.5 ng/L). Spatial analysis showed that the pollution level of PPCPs in the trunk stream was lower than that in most tributaries in the middle and lower reaches of the Yellow River (Henan section). The ecotoxicological risk assessment indicated that norfloxacin, azithromycin, estrone, and triclosan posed high risks to aquatic organisms (RQ > 1), roxithromycin and oxytetracycline imposed moderate risks (0.1 ≤ RQ < 1), and the tributary Jindi River had the highest mixed risk (MRQ = 222).


Assuntos
Cosméticos , Preparações Farmacêuticas , Rios , Poluição Química da Água , Cosméticos/efeitos adversos , Cosméticos/análise , Preparações Farmacêuticas/análise , Medição de Risco , Rios/química , Poluição Química da Água/efeitos adversos , Poluição Química da Água/análise
2.
Radiat Oncol ; 17(1): 182, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380378

RESUMO

BACKGROUND: Artificial intelligence (AI) algorithms are capable of automatically detecting contouring boundaries in medical images. However, the algorithms impact on clinical practice of cervical cancer are unclear. We aimed to develop an AI-assisted system for automatic contouring of the clinical target volume (CTV) and organs-at-risk (OARs) in cervical cancer radiotherapy and conduct clinical-based observations. METHODS: We first retrospectively collected data of 203 patients with cervical cancer from West China Hospital. The proposed method named as SegNet was developed and trained with different data groups. Quantitative metrics and clinical-based grading were used to evaluate differences between several groups of automatic contours. Then, 20 additional cases were conducted to compare the workload and quality of AI-assisted contours with manual delineation from scratch. RESULTS: For automatic CTVs, the dice similarity coefficient (DSC) values of the SegNet trained with incorporating multi-group data achieved 0.85 ± 0.02, which was statistically better than the DSC values of SegNet independently trained with the SegNet(A) (0.82 ± 0.04), SegNet(B) (0.82 ± 0.03) or SegNet(C) (0.81 ± 0.04). Moreover, the DSC values of the SegNet and UNet, respectively, 0.85 and 0.82 for the CTV (P < 0.001), 0.93 and 0.92 for the bladder (P = 0.44), 0.84 and 0.81 for the rectum (P = 0.02), 0.89 and 0.84 for the bowel bag (P < 0.001), 0.93 and 0.92 for the right femoral head (P = 0.17), and 0.92 and 0.91 for the left femoral head (P = 0.25). The clinical-based grading also showed that SegNet trained with multi-group data obtained better performance of 352/360 relative to it trained with the SegNet(A) (334/360), SegNet(B) (333/360) or SegNet(C) (320/360). The manual revision time for automatic CTVs (OARs not yet include) was 9.54 ± 2.42 min relative to fully manual delineation with 30.95 ± 15.24 min. CONCLUSION: The proposed SegNet can improve the performance at automatic delineation for cervical cancer radiotherapy by incorporating multi-group data. It is clinically applicable that the AI-assisted system can shorten manual delineation time at no expense of quality.


Assuntos
Planejamento da Radioterapia Assistida por Computador , Neoplasias do Colo do Útero , Feminino , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias do Colo do Útero/radioterapia , Estudos Retrospectivos , Inteligência Artificial , Redes Neurais de Computação , Órgãos em Risco
4.
ACS Nano ; 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36375012

RESUMO

The extensive spread of multidrug resistance to Gram-negative bacteria has become a huge threat to human health, where peptide-based antibacterial agents have emerged as a powerful star weapon. Here we report a lipopeptide (LP-20) constructed nanomicelle with a different antibacterial mechanism of membrane curvature modulation, which induced dynamic membrane fission resulting in acceleration and enhancement of antibacterial activity to clinically isolated ESKAPE strains, including multidrug-resistant (MDR) pathogens. The minimum inhibitory concentration was reduced to 2-10 µM, and the minimum duration for killing was shortened to less than an hour by LP-20. This is an improvement over antimicrobial peptides and traditional antibiotics, such as ciprofloxacin and tetracycline, significantly enhancing antibacterial activity for MDR, and we observed no acquisition of resistance for one month. This accelerated germicidal mechanism was attributed to multitargeting with lipopolysaccharides, phosphoethanolamine, phosphatidylglycerol, and cardiolipin, and the synergetic interactions induced a high curvature of the bacterial membrane, which facilitated simultaneously efficient damage to both inner and outer membrane. The LP-20 effectively prolonged the lifetime of myositis mice with Escherichia coli MDR and pneumonia mice with Klebsiella pneumoniae through a hepatic metabolism with ignorable toxicity. This study provides critical information for the fabrication of lipopeptide-based nano-antibiotics for the efficient control of intractable MDR caused by Gram-negative pathogens.

5.
CNS Neurosci Ther ; 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36353757

RESUMO

AIMS: Resistance to valproic acid (VPA) is a major challenge for epilepsy treatment. We aimed to explore the mechanism underlying this resistance. METHODS: Pentylenetetrazol-induced chronic epileptic rats were administered VPA (250 mg/Kg) for 14 days; rats with controlled seizure stages (seizure score14th-before ≤0) and latent time (latent time14th-before ≥0) were considered VPA-responsive, while the others were considered nonresponsive. Differentially expressed genes (DEGs) between the VPA-responsive and nonresponsive rat hippocampus transcriptomes were identified, and their functions were evaluated. The roles of postsynaptic density (PSD) and Homer1 were also determined. Furthermore, a subtype of Homer1 (Homer1b/c) was overexpressed or silenced in HT22 cells to determine its effect on VPA efficacy. Moreover, the membrane levels of mGluR1/5 directly bound to Homer1b/c were assessed. RESULTS: Overall, 264 DEGs commonly enriched in the PSD between VPA-responsive and nonresponsive rats. Among them, Homer1 was more highly expressed in the hippocampus of nonresponses compared to that of responses. Overexpression of Homer1b/c interrupted VPA efficacy by increasing reactive oxygen species production, lactate dehydrogenase release, and calcium content. Furthermore, it induced the overexpression of mGluR1 and mGluR5. CONCLUSION: Overexpression of Homer1b/c influenced VPA efficacy, revealing it could be a target to improve the efficacy of this treatment.

6.
Mol Neurobiol ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36449254

RESUMO

Failed communication between mitochondria and lysosomes causes dysfunctional mitochondria, which may induce mitochondria-related neurodegenerative diseases. Here, we show that RAB7A, a small GTPase of the Rab family, mediates the crosstalk between these two important organelles to maintain homeostasis in N2a cells treated with PrP106-126. Specifically, we demonstrate that mitophagy deficiency in N2a cells caused by PrP106-126 is associated with dysregulated RAB7A localization in mitochondria. Cells lacking RAB7A display decreased mitochondrial colocalization with lysosomes and significantly increased mitochondrial protein expression, resulting in inhibited mitophagy. In contrast, overexpression of GTP-bound RAB7A directly induces lysosome colocalization with mitochondria. Further study revealed that GTP-bound RAB7A protects mitochondrial homeostasis by supporting autophagosome biogenesis. Moreover, we suggest that depletion of RAB7A leads to gross morphological changes in lysosomes, which prevents autophagosome-lysosome fusion and interferes with the breakdown of autophagic cargo within lysosomes. Overexpression of GTP-bound RAB7A can also alleviate PrP106-126-induced morphological damage and dysfunction of mitochondria, reducing neuronal apoptosis. Collectively, our data demonstrate that RAB7A successfully drives mitochondria to the autophagosomal lumen for degradation, suggesting that the communication of proteotoxic stress from mitochondria to lysosomes requires RAB7A, as a signaling molecule, to establish a link between the disturbed mitochondrial network and its remodeling. These findings indicate that small molecules regulating mitophagy have the potential to modulate cellular homeostasis and the clinical course of neurodegenerative diseases. Proposed model of mitophagy regulated by RAB7A. (1) Accumulating PrP106-126 induced mitophagy. (2) RAB7A is recruited to mitochondria. (3) ATG5-12 and ATG9A (5) vesicles are recruited to the autophagosome formation sites in a RAB7A-dependent manner. The ATG5-12 complex recruits and anchors LC3-I to form active LC3-II (4), accelerating mitophagosomal formation. The ATG9A vesicles are thought to be a source of membranes for autophagosome assembly. The recruitment of proteins and lipids induces membrane expansion and subsequent closure to form the mitophagosome. (6) Maintenance of the normal low lysosomal PH depends on active (GTP-bound) RAB7A. (7) RAB7A recruits effector molecules responsible for tight membrane interactions, and directly or indirectly, the subsequent autophagosome merges with the lysosome, and the cargo is completely degraded.

7.
Org Lett ; 24(43): 8052-8056, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36281985

RESUMO

The incorporation of a germyl group and another functional fragment across the C═C bond is a challenging task due to the prevailing hydrogermylation reaction. Herein, an efficient copper-catalyzed three-component reaction of alkenes, germanium hydrides, and trimethylsilyl azide has been disclosed. This transformation allows the concomitant introduction of germyl and azide groups across the double bonds in a highly regioselective manner with tert-butyl hydroperoxides as the bystanding oxidant. The resulting ß-germyl azides could be easily converted into ß-germyl amine and 1,2,3-triazoles of significant value.

8.
Technol Health Care ; 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36278366

RESUMO

BACKGROUND: The medicine selection method is a critical and challenging issue in medical insurance decision-making. OBJECTIVES: This study proposed a real-world data-based multi-criteria decision analysis (MCDA) model with a hybrid entropic weight Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) algorithms to select satisfactory drugs. METHODS: The evaluation index includes two levels: primary criteria and sub-criteria. Firstly, we proposed six primary criteria to form the value health framework. The primary criteria's weights were derived from the policymakers' questionnaire. Meanwhile, clinically relevant sub-criteria were derived from high-quality (screened by GRADE scores) clinical-research literature. Their weights are determined by the entropy weight (EW) algorithm. Secondly, we split the primary criteria into six mini-EW-TOPSIS models. Then, we obtained six ideal closeness degree scores (ICDS) for each candidate drug. Thirdly, we get the total utility score by linear weighting the ICDS. The higher the utility score, the higher the ranking. RESULTS: A national multicenter real-world case study of the ranking of four generic antibiotics validated the proposed model. This model is verified by comparative experiments and sensitivity analysis. The whole ranking model was consistent and reliable. Based on these results, medical policymakers can intuitively and easily understand the characteristics of each drug to facilitate follow-up drug policy-making. CONCLUSION: The ranking algorithm combines the objective characteristics of medicine and policy makers' opinions, which can improve the applicability of the results. This model can help decision-makers, clinicians, and related researchers better understand the drug assessment process.

9.
Water Res ; 226: 119213, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36240711

RESUMO

Groundwater level (GWL) recovery in some semiarid regions, attributed to mitigation countermeasures for groundwater depletion, potentially causes nitrate accumulated in the vadose zone to be introduced into the aquifer. However, the extent to which GWL recovery affects interactions between the vadose zone and saturated aquifers, migration pathways of soil nitrogen and groundwater nitrate dynamics have not been explicitly determined. This study established a quasi-3D feedback model for the vadose zone-groundwater coupled system in a typical GWL recovery area and quantitatively evaluated the effects of GWL recovery on nitrate-N leaching fluxes via the vadose zone and groundwater nitrate-N dynamics. Within the framework of the integrated model, both the water/contaminant leaching fluxes and the depth to groundwater were exchanged at each flow time step. The obtained results reveal that the temporal changes in nitrate-N leaching fluxes depended on the behaviors of precipitation, farmland irrigation and lithology of the vadose zone, while its spatial patterns were determined by both the GWL undulation and the vertical profiles of nitrate-N content. Furthermore, the GWL recovery caused the magnitude of the nitrate-N leaching fluxes into the aquifer to increase by 44.4%. Along with the GWL recovery, the phreatic aquifer volume increased by 7.47%, and the nitrate-N mass herein increased by 40.06%, which was largely driven by the nitrate-N leaching flux. Consequently, the average groundwater nitrate-N concentration in the GWL recovery region increased by approximately 2.4 mg/L, apart from the artificial recharge route. This finding suggests that the intensified leaching of soil contaminants, given the circumstances of GWL recovery, has a negative effect on groundwater quality. An appropriate groundwater management scheme is therefore urgently required to achieve an optimal balance between GWL recovery and groundwater environment.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Nitratos/análise , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Solo , Óxidos de Nitrogênio
10.
Sci Rep ; 12(1): 17497, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36261461

RESUMO

The ice abrasive air jet is a clean surface treatment technology, which currently has limitations such as high energy consumption, uncontrollable particle size and hardness. Realizing the instant preparation and utilization of ice particles are crucial for solving the energy consumption problem. This paper based on the icing principle of heterogeneous nucleation, proposed a new method of ice making, the heat transfer mechanism of low temperature droplets was studied, and the method was proved to be feasible. Using the FLUENT solidification and melting model combined with the VOF model to calculate the freezing process of droplets, the effects of droplet particle size, initial temperature, and wall temperature on the freezing time were analyzed, and the calculation equation of the freezing time was determined, which was corrected by the icing test results. The results showed that the outside of the droplet freezes first, the liquid-solid boundary is parabolic, and the parabolic concavity increases with time and droplet size. In the freezing process, the larger the droplet size, the longer the droplet phase transition time; the higher the droplet initial temperature, the longer it took to reach the phase transition; the higher the wall temperature, the longer the ice formation time.

11.
Environ Monit Assess ; 194(12): 850, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36201087

RESUMO

The soil water characteristic curve (SWCC) is of great significance for studying the hydrological cycle, agricultural water management, and unsaturated soil mechanics. However, it is difficult to effectively obtain a large number of SWCCs because of the cumbersome and expensive determination experiments for SWCCs. Pedo-transfer functions (PTFs) established using soil physicochemical properties have become an effective method for solving this problem. However, due to the limitations of the establishment methods and the wide spatial variability of soil properties, it is still difficult to establish PTFs in a specific region. In order to establish the PTFs of SWCCs for the alluvial plain area of the lower reaches of the Yellow River, 233 soil samples were collected from the vadose zone in a typical area. These data were used as the data sources, and eight variables including clay, silt content, fractal dimension, bulk density, total porosity, pH value, organic matter content, and electrical conductivity were used as the influencing factors. By applying and comparing three machine learning algorithms, the PTFs of the SWCCs based on the random forest algorithm were obtained. Based on the Gini index of the random forest, the insensitive factors were eliminated and the optimal variable input mode was constructed. Based on the verification, there was little difference between the predicted water content and the measured water content. The determination coefficient R2 is 0.9308; the root mean square error (RMSE) is 0.0447; and the mean relative error (MRE) is 22.40%.


Assuntos
Rios , Solo , Argila , Monitoramento Ambiental/métodos , Aprendizado de Máquina , Solo/química , Água/análise
12.
Front Pharmacol ; 13: 919487, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36188573

RESUMO

Sirolimus is used to treat pediatric patients with PIK3CD mutation-related immunodeficiency disease. However, the initial dosages of sirolimus remain undecided. The present study aims to explore initial dosages in pediatric patients with PIK3CD mutation-related immunodeficiency disease. Pediatric patients with this disease were analyzed using the population pharmacokinetic (PPK) model and the Monte Carlo simulation. Body weight and concomitant use of posaconazole were included in the final PPK model, where, under the same weight, clearances of sirolimus were 1 : 0.238 between children without and children with posaconazole. Without posaconazole, the initial dosages of sirolimus were 0.07, 0.06, 0.05, and 0.04 mg/kg/day for body weights of 10-14, 14-25, 25-50, and 50-60 kg, respectively. With posaconazole, the initial dosages of sirolimus were 0.02 mg/kg/day for body weights of 10-60 kg. This is the first attempt to build a sirolimus PPK model for recommending initial dosages in children with PIK3CD mutation-related immunodeficiency disease, thereby providing a reference for individualized clinical drug administration.

13.
Front Pediatr ; 10: 888686, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36210931

RESUMO

Objectives: The hepatitis B vaccine comprises hepatitis B surface antigen (HBsAg) produced by transgenic yeast cells. There are few serious adverse events (SAE) reports after Hepatitis B vaccination. Methods: The authors searched the Chinese legal documents database for all SAE with Hepatitis B vaccination from January 2010 to January 2022. Results: All seven patients received yeast-derived recombinant hepatitis B vaccine. Three cases of myocarditis (death), 2 cases of interstitial pneumonia (death), and 2 cases of encephalitis. The mean time of onset of SAE was 8.3 ± 4.3 h after vaccination. Conclusion: The mechanism of vaccine-induced myocarditis may come from immune protein reactions. Based on the experience of Hepatitis B vaccine adverse events, we present new insights into the mechanism of myocarditis caused by the COVID-19 vaccine.

14.
J Oncol ; 2022: 4621240, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36268278

RESUMO

Purpose: The purpose of this study was to retrospectively review the outcomes of patients with high-risk endometrial cancer treated with adjuvant radiotherapy with concurrent paclitaxel and cisplatin (TP). Methods: Patients with endometrial cancer who underwent radical surgery were screened between Jan 2005 and Dec 2018. Patients with high-risk factors who received adjuvant chemoradiotherapy were included in the study. High risks included stage I, endometrioid-type grade 3 with deep myometrial invasion or lymphovascular space invasion (or both), endometrioid-type stage II to IVa, or stage I to III with serous or clear cell histology. The adjuvant treatment regimen included one cycle of TP chemotherapy, followed by pelvic intensity-modulated radiotherapy (IMRT) with concurrent TP, followed by an additional one cycle of TP. Failure free survival (FFS) and overall survival (OS) were estimated. Patterns of recurrence and occurrence of adverse events were described. Results: A total of 450 patients with high-risk endometrial cancer were screened, 231 of whom were included in this study. After a median follow-up of 70 months, the 5-year OS was 94.7%, and the 6-year OS was 91.8%. The 5-y and 6-y FFS were 90.8% and 87.9%, respectively, which were related to stage (P < 0.05). A total of 14 patients experienced tumor recurrence, including 7 pelvic recurrence and 7 distant metastases. Seven patients died, all due to tumor progression. A total of 164 patients (71%) completed the prescribed course of treatment. A total of 205 patients had adverse events, 46 patients (20%) had grade 1, 92 patients (40%) had grade 2, 49 patients (21%) had grade 3, and 18 patients (8%) had grade 4. There were 83 nonhematologic and 122 hematologic toxicities (26 grade 3 and 18 grade 4). Conclusion: Adjuvant pelvic radiotherapy combined with synchronous TP chemotherapy can achieve excellent long-term survival for high-risk endometrial cancer patients. Moreover, this combination therapy has good safety and feasibility, which is worthy of further study and verification.

15.
Pharmaceutics ; 14(9)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36145566

RESUMO

As one of the most frequent complications of critical illness, acute lung injury (ALI) carries a high risk of clinical morbidity and mortality. Cepharanthine (CPA) has significant anti-inflammatory activity, however, due to poor water solubility, low bioavailability, and short half-life, it fails to provide effective clinical management measures. Here, we explored the flexibility of an erythrocyte-anchoring strategy using CPA-encapsulated chitosan-coating nanoparticles (CPA-CNPs) anchored onto circulating erythrocytes for the treatment of ALI. CPA-CNPs adhered to erythrocytes successfully (E-CPA-CNPs) and exhibited high erythrocyte adhesion efficiency (>80%). Limited toxicity and favorable biocompatibility enabled further application of E-CPA-CNPs. Next, the reticuloendothelial system evasion features were analyzed in RAW264.7 macrophages and Sprague-Dawley rats. Compared with bare CPA-CNPs, erythrocyte-anchored CNPs significantly decreased cellular uptake in immune cells and prolonged circulation time in vivo. Notably, the erythrocyte-anchoring strategy enabled CNPs to be delivered and accumulated in the lungs (up to 6-fold). In the ALI mouse model, E-CPA-CNPs attenuated the progression of ALI by inhibiting inflammatory responses. Overall, our results demonstrate the outstanding advantages of erythrocyte-anchored CPA-CNPs in improving the pharmacokinetics and bioavailability of CPA, which offers great promise for a lung-targeted drug delivery system for the effective treatment of ALI.

16.
Comput Math Methods Med ; 2022: 7364126, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105239

RESUMO

Objective: To explore the molecular targets and mechanism of YuPingFeng (YPF) for the treatment of asthma by using network pharmacology and molecular docking. Methods: The potential active ingredients and relevant targets of YPF were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Asthma-related gene targets were retrieved from GeneCards, OMIM, DrugBank, PharmGKB, and TTD databases. The protein-protein (PPI) network between YPF and asthma common targets was constructed by SRING online database and Cytoscape software. GO and KEGG analyses were performed to explore the complicated molecular biological processes and potential pathways. Finally, a molecular docking approach was carried out to verify the results. Results: We obtained 100 potential targets of the 35 active ingredients in YPF and 1610 asthma-related targets. 60 YPF-asthma common targets were selected to perform PPI analysis. Seven core genes were screened based on two topological calculation methods. GO and KEGG results showed that the main pathways of YPF in treating asthma include TNF signaling pathway and PI3K-Akt signaling pathway. Finally, the molecular docking results indicated that the key ingredients of YPF had a good affinity with the relevant core genes. Conclusion: This study reflects the multicomponent, multitarget, and multipathway characteristics of YPF in treating asthma, providing a theoretical and scientific basis for the intervention of asthma by traditional Chinese medicine YPF.


Assuntos
Asma , Fosfatidilinositol 3-Quinases , Asma/tratamento farmacológico , Asma/genética , Medicamentos de Ervas Chinesas , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Tecnologia
17.
Comput Math Methods Med ; 2022: 1881176, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124167

RESUMO

Objective: Enteric-coated mycophenolate sodium (EC-MPS) is widely used in renal transplant recipients. There is a lack of study on the pharmacokinetics of this drug in children. This study is aimed at developing a population pharmacokinetic model of mycophenolic acid in children who were treated with EC-MPS after renal transplantation and to recommend initial dosage. Methods: Pediatric patients who had undergone renal transplantation and received EC-MPS were included. Data on demographic characteristics, biochemical tests, blood routine examinations, mycophenolic acid plasma concentrations, dosing amount and frequency of EC-MPS, and coadministered medications were retrospective collected from June 2018 to August 2019. Nonlinear mixed effect modeling methods were adopted to develop a population pharmacokinetic model with the data above. Additional data from September 2019 to July 2020 were used to validate the model. Simulations under different dosage regimen were conducted to evaluate the percentage of target attainment (PTA, AUC0-12h 30-60 mg·h/L). Results: A total of 96 pediatric patients aged at 13.3 (range 4.3-18.0) years were included in the modeling group. Data from 32 patients aged at 13.0 (range 3.6-18.3) years were used to validate the model. A one-compartment model with a double extravascular absorption was developed. Body surface area (BSA) was added as a covariate. Simulations showed that for different dosing regimens, the highest percentage of target attainment is around 50%. The best dosing regimen is 180 mg every 48 hours for patients with BSA of 0.22-0.46 m2, 180 mg every 24 hours with BSA of 0.47-0.67 m2, 180 mg every 24 hours with BSA of 0.68-0.96 m2, 360 mg every 24 hours with BSA of 0.97-1.18 m2, 540 mg every 24 hours with BSA of 1.19-1.58 m2, and 360 mg every 12 hours with BSA of 1.59-2.03 m2. Conclusion: BSA could affect the area under curve of mycophenolic acid with the administration of EC-MPS. Considering the inflexibility of the dosage form, future development of smaller amount per tablet suitable for younger children with BSA < 1.19 m2 is warranted.


Assuntos
Transplante de Rim , Ácido Micofenólico , Idoso , Área Sob a Curva , Superfície Corporal , Criança , Humanos , Imunossupressores/farmacocinética , Ácido Micofenólico/farmacocinética , Estudos Retrospectivos , Comprimidos com Revestimento Entérico
18.
Front Pharmacol ; 13: 869939, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935844

RESUMO

The present study aimed to explore the population pharmacokinetics and initial dose optimization of tacrolimus in children with severe combined immunodeficiency (SCID) undergoing hematopoietic stem cell transplantation (HSCT). Children with SCID undergoing HSCT treated with tacrolimus were enrolled for analysis. Population pharmacokinetics of tacrolimus was built up by a nonlinear mixed-effects model (NONMEM), and initial dose optimization of tacrolimus was simulated with the Monte Carlo method in children weighing <20 kg at different doses. A total of 18 children with SCID undergoing HSCT were included for analysis, with 130 tacrolimus concentrations. Body weight was included as a covariable in the final model. Tacrolimus CL/F was 0.36-0.26 L/h/kg from body weights of 5-20 kg. Meanwhile, we simulated the tacrolimus concentrations using different body weights (5-20 kg) and different dose regimens (0.1-0.8 mg/kg/day). Finally, the initial dose regimen of 0.6 mg/kg/day tacrolimus was recommended for children with SCID undergoing HSCT whose body weights were 5-20 kg. It was the first time to establish tacrolimus population pharmacokinetics in children with SCID undergoing HSCT; in addition, the initial dose optimization of tacrolimus was recommended.

19.
BMC Gastroenterol ; 22(1): 388, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978277

RESUMO

BACKGROUND: Intra-abdominal desmoplastic small round cell tumors (IADSRCT) are rare and aggressive neoplasia that are resistant to chemotherapy. Anlotinib is an oral multi-target tyrosine kinase inhibitor that also has anti-angiogenic and anti-proliferative properties. In this article, we report on a case showing effective and durable responses to chemotherapy combined with anlotinib in a young man with IADSRCT. CASE PRESENTATION: A 27-year-old man was admitted to our hospital complaining of a palpable periumbilical mass that had been present for longer than 4 months. The diagnosis of IADSRCT was confirmed by biopsy and immunohistochemistry. An extensive unresectable metastasis was found on the initial diagnosis. The patient received six cycles of chemotherapy combined with anlotinib, and maintenance therapy with anlotinib was recommended. Hematochezia, proteinuria and hypertension were observed, however, long-term maintenance therapy was well tolerated. A partial response was observed after two cycles of combined therapy and the patient was still alive with stable disease at the time of reporting. CONCLUSIONS: Chemotherapy combined with anlotinib plus anlotinib maintenance showed promising efficacy and manageable toxicity in the treatment of advanced IADSRCT.


Assuntos
Tumor Desmoplásico de Pequenas Células Redondas , Quinolinas , Adulto , Tumor Desmoplásico de Pequenas Células Redondas/tratamento farmacológico , Humanos , Indóis/uso terapêutico , Masculino , Inibidores de Proteínas Quinases/farmacologia , Quinolinas/uso terapêutico
20.
Artigo em Inglês | MEDLINE | ID: mdl-35954621

RESUMO

The baseflow of the Yellow River is vital and important for water resource management and for understanding the hydrological cycle and ecohydrology setting in this arid and semi-arid basin. This study uses a Lyne and Hollick digital filtering technique to investigate the behaviors of the baseflow and the baseflow index in the upper reaches of the Yellow River Basin (China). The observed streamflow discharges along the river were used to analyze the baseflow trend, persistence, and periodic characteristics during the period of 1950-2000. The results show that the average baseflow and BFI in the upper reaches of the Yellow River exhibit a decreasing trend and will continue to decline in the future. Generally, the annual average baseflow and BFI for the most upstream areas of the Yellow River show little difference, while the baseflow and BFI exhibit significant differences for the downstream areas. The filtered annual baseflow varied between 128 × 108 m3/year and 193 × 108 m3/year for the Yellow River. The BFI ranged from 0.54 to 0.65, with an average of 0.60. This indicates that on average, 60% of the long-term streamflow is likely controlled by groundwater discharge and shallow subsurface flow. Statistics show that two periodic variations were observed in the baseflow evolution process. The results indicate that on average, the first and second main cycles of baseflow behaviors occur at 28 years and 12-17 years, respectively. Correspondingly, the estimation indicates that the abrupt change points tend to appear in the 1960s, the 1980s, and the 1990s. An improved understanding of baseflow behaviors can help guide future strategies to manage the river regime, its water resources, and water quality.


Assuntos
Água Subterrânea , Movimentos da Água , China , Monitoramento Ambiental , Rios
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