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Band alignment engineering is crucial for facilitating charge separation and transfer in optoelectronic devices, which ultimately dictates the behavior of Van der Waals heterostructures (vdWH)-based photodetectors and light emitting diode (LEDs). However, the impact of the band offset in vdWHs on important figures of merit in optoelectronic devices has not yet been systematically analyzed. Herein, the regulation of band alignment in WSe2/Bi2Te3- xSex vdWHs (0 ≤ x ≤ 3) is demonstrated through the implementation of chemical vapor deposition (CVD). A combination of experimental and theoretical results proved that the synthesized vdWHs can be gradually tuned from Type I (WSe2/Bi2Te3) to Type III (WSe2/Bi2Se3). As the band alignment changes from Type I to Type III, a remarkable responsivity of 58.12 A W-1 and detectivity of 2.91×1012 Jones (in Type I) decrease in the vdWHs-based photodetector, and the ultrafast photoresponse time is 3.2 µs (in Type III). Additionally, Type III vdWH-based LEDs exhibit the highest luminance and electroluminescence (EL) external quantum efficiencies (EQE) among p-n diodes based on Transition Metal Dichalcogenides (TMDs) at room temperature, which is attributed to band alignment-induced distinct interfacial charge injection. This work serves as a valuable reference for the application and expansion of fundamental band alignment principles in the design and fabrication of future optoelectronic devices.
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BACKGROUND: Traumatic brain injury (TBI), which is the brain impairment and lesion caused by the external force injuring the head and the underlying brain, can cause pediatric death, disability, neurological disorders, and even lifelong disability. This study was to explore the effect of riboflavin (RF) on neurological rehabilitation and functional recovery after TBI. METHODS: The rat models of TBI were constructed by treating rats with controlled cortical impact (CCI). By treating TBI rats with RF, we investigated whether the administration of RF would affect the sensorimotor function and cognitive ability recovery through adhesive removal test, modified neurological severity score (mNSS), corner test, wire-grip test and the Morris water maze. The effects of RF on lesion volume and water content were investigated using hematoxylin and eosin (H&E) staining and wet-dry method. The Nissl staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining were used to demonstrate the effect of RF on neural apoptosis. Inflammation-related cytokines of interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß1 were measured by enzyme-linked immunosorbent assay (ELISA) to evaluate the effect of RF on neuroinflammation. The impact of RF on oxidative stress was assessed by measuring malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, and the platelet endothelial cell adhesion molecule-1 (CD31) staining for observing vessel density, the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) for measuring vascular endothelial growth factor (VEGF) mRNA expression and western blot for VEGF protein expression were used for evaluated angiogenesis. RESULTS: The administration of RF could facilitate the recovery of neurological function by promoting the recovery of sensorimotor function and cognitive ability (p < 0.05). Furthermore, RF could reduce the lesion volume and water content after TBI and ameliorate neural apoptosis, neuroinflammation, and oxidative stress (p < 0.05). Finally, RF increased vessel density (p < 0.01) and VEGF levels (p < 0.01) in brain tissues after TBI, promoting angiogenesis. CONCLUSION: RF benefits neurological rehabilitation after TBI by promoting neurological function recovery, ameliorating the pathogenesis after TBI, and facilitating brain vascular remodeling. These findings provide a novel mechanism for RF treating pediatric TBI.
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Lesões Encefálicas Traumáticas , Riboflavina , Animais , Ratos , Lesões Encefálicas Traumáticas/reabilitação , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/fisiopatologia , Riboflavina/farmacologia , Riboflavina/uso terapêutico , Masculino , Humanos , Ratos Sprague-Dawley , Criança , Modelos Animais de Doenças , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Citocinas/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacosRESUMO
Two-dimensional (2D) transition metal dichalcogenide (TMD) heterostructures have attracted a lot of attention due to their rich material diversity and stack geometry, precise controllability of structure and properties, and potential practical applications. These heterostructures not only overcome the inherent limitations of individual materials but also enable the realization of new properties through appropriate combinations, establishing a platform to explore new physical and chemical properties at micro-nano-pico scales. In this review, we systematically summarize the latest research progress in the synthesis, modulation, and application of 2D TMD heterostructures. We first introduce the latest techniques for fabricating 2D TMD heterostructures, examining the rationale, mechanisms, advantages, and disadvantages of each strategy. Furthermore, we emphasize the importance of characteristic modulation in 2D TMD heterostructures and discuss some approaches to achieve novel functionalities. Then, we summarize the representative applications of 2D TMD heterostructures. Finally, we highlight the challenges and future perspectives in the synthesis and device fabrication of 2D TMD heterostructures and provide some feasible solutions.
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Uranium mainly comes from ISL of sandstone-type uranium deposits in China. The change of porosity and permeability caused by blockage of ore-bearing strata is one of the most serious problems in acid ISL of uranium. In this paper, the groundwater tracer test was carried out before and 1 year after ISL to explore the pore and permeability evolution characteristics of the ore-bearing layer during ISL. The test results showed that the leaching solution migrated along two seepage channels and the water-bearing medium was isotropic. After 1 year of ISL, the flow rate of the leaching solution decreased obviously. However, the flow rate of the leaching solution in slower channel decreased more than that in the faster channel in all directions, which was caused by the more adequate chemical reactions between the leaching solution and the minerals of the ore-bearing layer and the more corresponding precipitation in the slower channel. In addition, the flow rate along the direction of groundwater flow decreased less than that in the direction of vertical groundwater flow. This was closely related to the transformation of aquifer medium by hydrodynamic field. Initial stage of ISL, the occurrence of plugging is closely related to the precipitation-dissolution process of iron and aluminum minerals under the change of pH, which is accompanied by the continuous precipitation of gypsum.
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Água Subterrânea , Mineração , Urânio , Urânio/química , China , Água Subterrânea/química , Permeabilidade , Movimentos da Água , Poluentes Radioativos da Água/análise , Poluentes Radioativos da Água/química , PorosidadeRESUMO
BACKGROUND: Complete fractures and dislocations of the lower cervical spine are usually associated with severe spinal cord injury. However, a very small number of patients do not have severe spinal cord injury symptoms, patients with normal muscle strength or only partial nerve root symptoms, known as "lucky fracture dislocation". The diagnosis and treatment of such patients is very difficult. Recently, we successfully treated one such patient. CASE PRESENTATION: A 73-year-old male patient had multiple neck and body aches after trauma, but there was sensory movement in his limbs. However, preoperative cervical radiographs showed no significant abnormalities, and computed tomography (CT) and magnetic resonance imaging (MRI) confirmed complete fracture and dislocation of C7. Before operation, the halo frame was fixed traction, but the reduction was not successful. Finally, the fracture reduction and internal fixation were successfully performed by surgery. The postoperative pain of the patient was significantly relieved, and the sensory movement of the limbs was the same as before. Two years after surgery, the patient's left little finger and ulnar forearm shallow sensation recovered, and the right flexion muscle strength basically returned to normal. CONCLUSION: This case suggests that when patients with trauma are encountered in the clinic, they should be carefully examined, and the presence of cervical fracture and dislocation should not be ignored because of the absence of neurological symptoms or mild symptoms. In addition, positioning during handling and surgery should be particularly avoided to increase the risk of paralysis.
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Vértebras Cervicais , Fraturas da Coluna Vertebral , Humanos , Masculino , Idoso , Vértebras Cervicais/lesões , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/complicações , Fixação Interna de Fraturas/métodos , Tomografia Computadorizada por Raios X , Fratura-Luxação/cirurgia , Fratura-Luxação/diagnóstico por imagem , Fratura-Luxação/complicações , Resultado do Tratamento , Luxações Articulares/cirurgia , Luxações Articulares/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Fear memory extinction is closely related to insomnia. Repetitive transcranial magnetic stimulation (rTMS) is safe and effective for treating insomnia disorder (ID), and it has been shown to be an efficient method for modulating fear extinction. However, whether rTMS can improve fear extinction memory in ID patients remains to be studied. In this study, we specifically aim to (1) show that 1 Hz rTMS stimulation could improve fear extinction memory in ID patients and (2) examine whether changes in sleep mediate this impact. METHODS AND DESIGN: We propose a parallel group randomised controlled trial of 62 ID participants who meet the inclusion criteria. Participants will be assigned to a real rTMS group or a sham rTMS group. The allocation ratio will be 1:1, with 31 subjects in each group. Interventions will be administered five times per week over a 4-week period. The assessments will take place at baseline (week 0), post-intervention (week 4), and 8-week follow-up (week 8). The primary outcome measure of this study will be the mean change in the Pittsburgh Sleep Quality Index (PSQI) scores from baseline to post-intervention at week 4. The secondary outcome measures include the mean change in skin conductance response (SCR), fear expectation during fear extinction, Insomnia Severity Index (ISI), Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS). DISCUSSION: This study will be the first examination of the impact of rTMS on fear memory extinction in ID patients. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR2300076097. Registered on 25 September 2021.
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Extinção Psicológica , Medo , Ensaios Clínicos Controlados Aleatórios como Assunto , Distúrbios do Início e da Manutenção do Sono , Estimulação Magnética Transcraniana , Humanos , Distúrbios do Início e da Manutenção do Sono/terapia , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Estimulação Magnética Transcraniana/métodos , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade , Feminino , Masculino , Memória , Adulto Jovem , Fatores de Tempo , Adolescente , SonoRESUMO
Background: We aimed to observe the effect of extended care on improving motor function and activities of daily living of stroke-induced hemiplegic patients. Methods: Patients clinically diagnosed as stroke with hemiplegia and hospitalized in the Neurology Department at Tianjin Haibin People's Hospital, China from 2019 to 2020 were selected. One hundred twenty patients were enrolled and randomly divided into the intervention group (60 patients) and the control group (60 patients). The control group was given routine rehabilitation treatment and care. Based on routine rehabilitation treatment and care, the intervention group was given transitional care. After discharge, the patients were followed up. Barthel indexes (BIs) were collected to evaluate the activities of daily living of patients. The Fugl-Meyer Motor Function Assessment (FMA) was adopted to evaluate the patients' motor function. Results: There was no statistically significant difference in the total BI scores between the two groups of patients at the two time points before intervention and at discharge. The total scores of the intervention group were higher than those of the control group after 1 month and 3 months of discharge, and the difference was statistically significant (P<0.05). There was no statistically significant difference in total FMA scores between the two groups of patients before intervention, indicating comparability. After 3 months of discharge, the total FMA score of the intervention group patients was higher than that of the control group, and the differences were statistically significant (P<0.05). Conclusion: Continuous care can effectively improve motor function and daily living ability of stroke patients with hemiplegia.
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Transition-metal dichalcogenides (TMDCs), as emerging optoelectronic materials, necessitate the establishment of an experimentally viable system to study their interaction with light. In this study, we propose and analyze a WS2/PMMA/Ag planar Fabry-Perot (F-P) cavity, enabling the direct experimental measurement of WS2 absorbance. By optimizing the structure, the absorbance of A exciton of WS2 up to 0.546 can be experimentally achieved, which matches well with the theoretical calculations. Through temperature and thermal expansion strain induced by temperature, the absorbance of the A exciton can be tuned in situ. Furthermore, temperature-dependent photocurrent measurements confirmed the consistent absorbance of the A exciton under varying temperatures. This WS2/PMMA/Ag planar structure provides a straightforward and practical platform for investigating light interaction in TMDCs, laying a solid foundation for future developments of TMDC-based optoelectronic devices.
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BACKGROUND: Comorbid anxiety disorders and anxious distress are highly prevalent among individuals with major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. Few studies have evaluated the therapeutic effects of High-definition transcranial direct current stimulation (HD-tDCS) on depressive and anxiety symptoms among MDD patients with ADS. The current randomized controlled trial aims to assess the efficacy of HD-tDCS as an augmentation therapy with antidepressants compared to sham-control in subjects of MDD with ADS. METHODS: MDD patients with ADS will be recruited and randomly assigned to the active HD-tDCS or sham HD-tDCS group. In both groups, patients will receive the active or sham intervention in addition to their pre-existing antidepressant therapy, for 2 weeks with 5 sessions per week, each lasting 30 min. The primary outcome measures will be the change of depressive symptoms, clinical response, and the remission rate as measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before and after the intervention and at the 2nd and 6th week after the completed intervention. Secondary outcome measures include anxiety symptoms, cognitive symptoms, disability assessment, and adverse effects. DISCUSSION: The HD-tDCS applied in this trial may have treatment effects on MDD with ADS and have minimal side effects. TRIAL REGISTRATION: The trial protocol is registered with www.chictr.org.cn under protocol registration number ChiCTR2300071726. Registered 23 May 2023.
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Transtorno Depressivo Maior , Ensaios Clínicos Controlados Aleatórios como Assunto , Estimulação Transcraniana por Corrente Contínua , Humanos , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/diagnóstico , Estimulação Transcraniana por Corrente Contínua/métodos , Método Duplo-Cego , Resultado do Tratamento , Adulto , Antidepressivos/uso terapêutico , Pessoa de Meia-Idade , Masculino , Feminino , Ansiedade/terapia , Ansiedade/psicologia , Ansiedade/diagnóstico , Transtornos de Ansiedade/terapia , Transtornos de Ansiedade/psicologia , Adulto Jovem , Terapia Combinada , AdolescenteRESUMO
The occurrence and development of diabetic vascular diseases are closely linked to inflammation-induced endothelial dysfunction. Puerarin (Pue), the primary component of Pueraria lobata, possesses potent anti-inflammatory properties. However, its vasoprotective role remains elusive. Therefore, we investigated whether Pue can effectively protect against vascular damage induced by diabetes. In the study, Pue ameliorated lipopolysaccharide-adenosine triphosphate (LPS-ATP) or HG-primed cytotoxicity and apoptosis, while inhibited reactive oxygen species (ROS)-mediated NLR family pyrin domain containing 3 (NLRP3) inflammasome in HUVECs, as evidenced by significantly decreased ROS level, NOX4, Caspase-1 activity and expression of NLRP3, GSDMD, cleaved caspase-1, IL-1ß and IL-18. Meanwhile, ROS inducer CoCI2 efficiently weakened the effects of Pue against LPS-ATP-primed pyroptosis. In addition, NLRP3 knockdown notably enhanced Pue's ability to suppress pyroptosis in LPS-ATP-primed HUVECs, whereas overexpression of NLRP3 reversed the inhibitory effects of Pue. Furthermore, Pue inhibited the expression of ROS and NLRP3 inflammasome-associated proteins on the aorta in type 2 diabetes mellitus rats. Our findings indicated that Pue might ameliorate LPS-ATP or HG-primed damage in HUVECs by inactivating the ROS-NLRP3 signalling pathway.
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Trifosfato de Adenosina , Células Endoteliais da Veia Umbilical Humana , Inflamassomos , Isoflavonas , Lipopolissacarídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Espécies Reativas de Oxigênio , Transdução de Sinais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Humanos , Animais , Transdução de Sinais/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Ratos , Masculino , Trifosfato de Adenosina/metabolismo , Inflamassomos/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Piroptose/efeitos dos fármacos , Ratos Sprague-Dawley , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Glucose/metabolismo , Apoptose/efeitos dos fármacosRESUMO
Following the publication of this article, an interested reader drew to the authors' attention that the western blots in Fig. 4B on p. 3560 and Fig. 6B on p. 3562 shared remarkably similar data (including both the GAPDH and the FAM172A blots in Fig. 4B), such that these data were likely to have been derived from the same original source. Upon asking the authors to provide an explanation, the authors realized that these errors inadvertently arose during the process of assembling these figures. Due to a mislabelling of the files, representative blots for FAM172A and GAPDH were chosen incorrectly for Fig. 4B. The authors had retained their original data, however, and were also able to present to the Editorial Office for our perusal the uncropped versions of their western blots, which resolved any other potential issues of anomalies associated with the data. The revised version of Fig. 4, now showing alternative data for Fig. 4B, is shown on the next page (note that, in the repeated experiment, relative to the original version of this figure the miR27a, miR27ainhibitor and negative control experiments were run on different lanes of the gel). Also note that the errors made in terms of assembling the data in Fig. 4 did not greatly affect either the results or the conclusions reported in this paper, and all the authors agree to the publication of this corrigendum. The authors regret that these errors went unnoticed prior to the publication of their article, are grateful to the Editor of Oncology Reports for granting them this opportunity to publish a corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 37: 35543564, 2017; DOI: 10.3892/or.2017.5592].
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Photoimmunotherapy is a promising cancer treatment modality. While potent 1-e- oxidative species are known to induce immunogenic cell death (ICD), they are also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post-generation radical reinforcement. Namely, non-oxidative radicals are first generated and subsequently activated into powerful oxidative radicals to induce ICD. Here, we developed a photo-triggered molecular donor (NPCD565) of nitrosoperoxycarbonate (ONOOCO2 -), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO2 - is released along with a bright rhodamine dye (RD565), whose fluorescence is a reliable and convenient build-in reporter for the localization, kinetics, and dose of ONOOCO2 - generation. Upon photolysis of NPCD565 in 4T1 cells, damage-associated molecular patterns (DAMPs) indicative of ICD were observed and confirmed to exhibit immunogenicity by induced maturation of dendritic cells. In vivo studies with a bilateral tumor-bearing mouse model showcased the potent tumor-killing capability of NPCD565 of the primary tumors and growth suppression of the distant tumors. This work unveils the potent immunogenicity of ONOOCO2 -, and its donor (NPCD565) has broad potential for photo-immunotherapy of cancer.
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Carbono , Imunoterapia , Rodaminas , Animais , Camundongos , Rodaminas/química , Carbono/química , Fototerapia , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Corantes Fluorescentes/químicaRESUMO
PURPOSE: The present study aims to determine the molecular mechanism mediated by RAD51 antisense RNA 1 (RAD51-AS1) in ovarian cancer (OvCA). METHODS: The data associated with RAD51-AS1 in OvCA were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Relative expression of RAD51-AS1 was detected. Determination of cell proliferation, metastasis, and invasion was performed by cell counting, colony formation, would-healing, and transwell invasion assays. Protein levels were detected by western blotting. The molecular mechanism mediated by RAD51-AS1 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assays. Subcutaneous tumorigenesis models were used to confirm the function of RAD51-AS1 in vivo. RESULTS: Data from TCGA and GEO showed that RAD51-AS1 was associated with poor prognosis in OvCA patients and DNA repair, cell cycle, focal adhesion, and apoptosis in SKOV3.ip cells. High levels of RAD51-AS1 were detected in OvCA cells. Overexpressing RAD51-AS1 enhanced the proliferative, invading, and migratory capabilities of OvCA cells in vitro while silencing RAD51-AS1 exhibited the opposite effects. Mechanically, RAD51-AS1 elevated eukaryotic initiation factor 5A2 (EIF5A2) expression as a sponge for microRNA (miR)-140-3p. Finally, the role of RAD51-AS1 was verified by subcutaneous tumorigenesis models. CONCLUSION: RAD51-AS1 promoted OvCA progression by the regulation of the miR-140-3p/EIF5A2 axis, which illustrated the potential therapeutic target for OvCA.
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MicroRNAs , Neoplasias Ovarianas , RNA Longo não Codificante , Feminino , Humanos , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/genética , Rad51 Recombinase/genética , RNA Longo não Codificante/genéticaRESUMO
Intestinal adhesion is one of the complications that occurs more frequently after abdominal surgery. Postsurgical intestinal adhesion (PIA) can lead to a series of health problems, including abdominal pain, intestinal obstruction, and female infertility. Currently, hydrogels and nanofibrous films as barriers are often used for preventing PIA formation; however, these kinds of materials have their intrinsic disadvantages. Herein, we developed a dual-structure drug delivery patch consisting of poly lactic-co-glycolic acid (PLGA) nanofibers and a chitosan hydrogel (NHP). PLGA nanofibers loaded with deferoxamine mesylate (DFO) were incorporated into the hydrogel; meanwhile, the hydrogel was loaded with anti-inflammatory drug dexamethasone (DXMS). The rapid degradation of the hydrogel facilitated the release of DXMS at the acute inflammatory stage of the early injury and provided effective anti-inflammatory effects for wound sites. Moreover, PLGA composite nanofibers could provide sustained and stable release of DFO for promoting the peritoneal repair by the angiogenesis effects of DFO. The in vivo results indicated that NHP can effectively prevent PIA formation by restraining inflammation and vascularization, promoting peritoneal repair. Therefore, we believe that our NHP has a great potential application in inhibition of PIA.
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Dexametasona , Sistemas de Liberação de Medicamentos , Hidrogéis , Nanofibras , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Nanofibras/química , Nanofibras/uso terapêutico , Hidrogéis/química , Hidrogéis/farmacologia , Hidrogéis/administração & dosagem , Aderências Teciduais/prevenção & controle , Animais , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Dexametasona/farmacologia , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Quitosana/química , Quitosana/farmacologia , Intestinos/efeitos dos fármacos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Ratos Sprague-Dawley , Camundongos , Feminino , RatosRESUMO
Eltrombopag was approved as a first-line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic anemia (AA), especially non-severe AA (NSAA), are limited. We performed a prospective, single-arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with NSAA, SAA, and very severe AA (VSAA). The efficacy and safety were assessed every 3 months. The population pharmacokinetic (PPK) model was used to depict the pharmacokinetic profile of eltrombopag. Twenty-three AA children with an average age of 7.9 (range of 3.0-14.0) years were enrolled. The response (complete and partial response) rate was 12.5%, 50.0%, and 100.0% after 3, 6, and 12 months in patients with NSAA. For patients with SAA and VSAA, these response rates were 46.7%, 61.5%, and 87.5%. Hepatotoxicity occurred in one patient. Fifty-three blood samples were used to build the PPK model. Body weight was the only covariate for apparent clearance (CL/F) and volume of distribution. The allele-T carrier of adenosine triphosphate-binding cassette transporter G2 was found to increase eltrombopag's clearance. However, when normalized by weight, the clearance between the wild-type and variant showed no statistical difference. In patients with response, children with NSAA exhibited lower area under the curve from time zero to infinity, higher CL/F, and higher weight-adjusted CL/F than those with SAA or VSAA. However, the differences were not statistically significant. The results may support further individualized treatment of eltrombopag in children with AA.
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Anemia Aplástica , Benzoatos , Hidrazinas , Pirazóis , Humanos , Benzoatos/farmacocinética , Benzoatos/efeitos adversos , Benzoatos/uso terapêutico , Benzoatos/administração & dosagem , Hidrazinas/farmacocinética , Hidrazinas/efeitos adversos , Hidrazinas/uso terapêutico , Criança , Anemia Aplástica/tratamento farmacológico , Pirazóis/farmacocinética , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/sangue , Masculino , Pré-Escolar , Feminino , Adolescente , Estudos Prospectivos , Resultado do Tratamento , Modelos Biológicos , Receptores de Trombopoetina/agonistas , Índice de Gravidade de Doença , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP3A/genéticaRESUMO
Lin, Tian, Huaping Jia, Yunming Li, Yongxing Xu, Bei Zhao, Dong Zheng, Hongfeng Yan, Meihui Zhao, Yanlei Li, Liping Xia, Fengxia Zhou, Cuiping Liu, Ke Ma, Ma Mi, and Jianwen Gu. Epidemiological survey of congenital heart disease among children aged from 2 to 18 in Suo County, Nagqu, Tibet. High Alt Med Biol. 00:000-000, 2024. Background: Studies have reported the prevalence of congenital heart disease (CHD) in parts of Tibet, but relative epidemiological surveys are rare. We aimed to explore the prevalence of CHD in children and its relationship with family history in Suo County, Nagqu, Tibet, an altitude of 3,980 meters. Methods: We recruited 4,002 children aged 2-18 years. Subjects underwent a family history investigation, cardiac auscultation, and clinical manifestation examination and then received echocardiographic screening. Results: The prevalence of CHD among children in Suo County was 0.97% (39 cases), much higher than the prevalence at sea level. The most common subtype was atrial septal defect, accounting for 53.9% of CHD, followed by patent ductus arteriosus (33.3%) and ventricular septal defect (12.8%). We also found that children whose mothers had previously borne children with CHD had a higher risk of CHD than those without (p = 0.002); other factors related to CHD during pregnancy, such as smoking, drinking, drug use, and viral infection, showed no statistical differences between children with and without CHD. Conclusions: The prevalence of CHD in children in Suo County is much higher than at low altitude, consisting mostly of simple forms with left-to-right shunt, with rare complex CHD. These results support implementing diagnostic and treatment plans to prevent CHD in Suo County.
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Altitude , Cardiopatias Congênitas , Humanos , Tibet/epidemiologia , Feminino , Masculino , Cardiopatias Congênitas/epidemiologia , Criança , Prevalência , Adolescente , Pré-Escolar , Fatores de Risco , Comunicação Interatrial/epidemiologia , EcocardiografiaRESUMO
Multiple structural phases of tellurium (Te) have opened up various opportunities for the development of two-dimensional (2D) electronics and optoelectronics. However, the phase-engineered synthesis of 2D Te at the atomic level remains a substantial challenge. Herein, we design an atomic cluster density and interface-guided multiple control strategy for phase- and thickness-controlled synthesis of α-Te nanosheets and ß-Te nanoribbons (from monolayer to tens of µm) on WS2 substrates. As the thickness decreases, the α-Te nanosheets exhibit a transition from metallic to n-type semiconducting properties. On the other hand, the ß-Te nanoribbons remain p-type semiconductors with an ON-state current density (ION) up to ~ 1527 µA µm-1 and a mobility as high as ~ 690.7 cm2 V-1 s-1 at room temperature. Both Te phases exhibit good air stability after several months. Furthermore, short-channel (down to 46 nm) ß-Te nanoribbon transistors exhibit remarkable electrical properties (ION = ~ 1270 µA µm-1 and ON-state resistance down to 0.63 kΩ µm) at Vds = 1 V.
RESUMO
Continuous 6-mercaptopurine (6-MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose-limiting hematopoietic toxicity. However, evidence-based guidelines for gene-based 6-MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open-label, active-controlled clinical trial randomly assigned Chinese children with low- or intermediate-risk ALL in a 1:1 ratio to receive TPMT-NUDT15 gene-based dosing of 6-MP (N = 44, 10 to 50 mg/m2 /day) or standard dosing (N = 44, 50 mg/m2 /day) during maintenance therapy. The primary end point was the incidence of 6-MP myelosuppression in both groups. Secondary end points included frequencies of 6-MP hepatotoxicity, duration of myelosuppression and leukopenia, event-free survival, and steady-state concentrations of active metabolites (6-thioguaninenucleotides and 6-methylmercaptopurine nucleotides) in erythrocytes. A 2.2-fold decrease in myelosuppression, the primary end point, was observed in the gene-based-dose group using ~ 50% of the standard initial 6-MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene-based-dose group had a significantly lower risk of developing thiopurine-induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady-state concentrations of active metabolites in erythrocytes between the two groups. TPMT- and NUDT15-based dosing of 6-MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.
Assuntos
População do Leste Asiático , Mercaptopurina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Antimetabólitos Antineoplásicos/efeitos adversos , Doenças da Medula Óssea , Doença Hepática Induzida por Substâncias e Drogas , China/epidemiologia , Leucopenia/induzido quimicamente , Leucopenia/epidemiologia , Mercaptopurina/efeitos adversos , Metiltransferases , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologiaRESUMO
Although the management of microbes in drinking water is of paramount importance for public health, there remain challenges in comprehensively examining pathogenic bacteria in the water supply system at the species level. In this study, high-throughput sequencing of nearly full-length 16S rRNA genes was performed to investigate the changes of the water bacterial community in three large-scale drinking water treatment plants (DWTPs) and their corresponding distribution systems during winter and summer. Our findings revealed significant differences in the bacterial community structure between winter and summer water samples for each DWTP and its distribution management area (DMA). In the groundwater-fed DWTP, selective enrichment of mycobacterial species was observed in both seasons, and the subsequent DMA also exhibited strong selection for specific mycobacterial species. In one of the surface water-fed DWTPs, certain Legionella species present in the source water in winter were selectively enriched in the bacterial community after pre-oxidation, although they were susceptible to the subsequent purification steps. A variety of putative pathogenic species (n = 83) were identified based on our pathogen identification pipeline, with the dominant species representing opportunistic pathogens commonly found in water supply systems. While pathogen removal primarily occurred during the purification processes of DWTPs, especially for surface water-fed plants, the relative abundance of pathogenic bacteria in the DMA water flora was lower than that in the DWTP effluent flora, indicating a diminished competitiveness of pathogens within the DMA ecosystem.