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Background: Neural cell damage is an important cause of exacerbation of depression symptoms caused by hypoxia, but the mechanism behind it is still unclear. The purpose of this study is to elucidate the role of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)/mitofusin-2 (MFN2) signaling axis in the development of depression in mice under hypoxia. Methods: Male Institute of Cancer Research mice (age, 6 weeks) were assigned to the normal group, chronic unpredictable mild stress group (CUMS group), or CUMS + hyper-hypoxia group (CUMS + H group). Mice in the CUMS and CUMS + H groups were exposed to CUMS for 28 days. Additionally, mice in the CUMS + H group were exposed to acute hyper-hypoxia from Day 21 for 7 days. After a total of 28 days, behavioral experiments were conducted. All mice were anesthetized and sacrificed. Levels of brain tissue interleukin (IL)-6, reactive oxygen species (ROS), adenosine triphosphate (ATP), and serotonin (5-HT) were analyzed. Results: As compared to the CUMS group, mice in the CUMS + H group had increased IL-6 and ROS levels, but lower open-field activity, preference for sucrose, hippocampal neuronal membrane potential, ATP, and 5-HT levels, as well as MFN2 and PGC1α levels. Conclusions: Acute hyper-hypoxia plays an important role in the development of depression via the IL-6/PGC1α/MFN2 signaling pathway.
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BACKGROUND: Periodontal tissue loss is the main reason for tooth mobility and loss caused by periodontal disease. Dental follicle stem cells (DFSCs) have significant therapeutic potential in periodontal regeneration, which maybe mainly depends on their potent immunomodulatory capacity. Consequently, this study aims to elucidate the impact of implanted xenogenous DFSCs on innate immune responses during early and late stages in the periodontal defect repair period. METHODS: To trace and investigate the immunomodulation mechanisms of DFSCs in vivo, DFSCs were engineered (E-DFSCs) using lentiviral vectors expressing CD63-enhanced green fluorescent protein (CD63-EGFP) and ß-Actin-mCherry protein (ACTB-mCherry) to exhibit green and red fluorescence. The biological characteristics and functions of E-DFSCs were verified by proliferation, differentiation, and co-culture experiments in vitro. In vivo, the periodontal regeneration capacity of E-DFSCs was detected by implantation of murine periodontal defect model, and the response of innate immune cells was detected at the 1st, 3rd, and 5th days (early stage) and 4th week (late stage) after implantation. RESULTS: In vitro assessments showed that E-DFSCs retain similar properties to their non-engineered counterparts but exhibit enhanced macrophage immunomodulation capability. In mice models, four-week micro-CT and histological evaluations indicated that E-DFSCs have equivalent efficiency to DFSCs in periodontal defect regeneration. At the early stage of repair in mice periodontal defect, fluorescence tracking showed that implanted E-DFSCs might primarily activate endogenous cells through direct contact and indirect actions, and most of these cells are myeloperoxidase-positive neutrophils. Additionally, compared with the control group, the neutrophilic infiltration and conversion of N2-type were significantly increased in the E-DFSC group. At the late stage of defect regeneration, more M2-type macrophages, fewer TRAP + osteoclasts, and an upregulated OPG/RANKL ratio were detected in the E-DFSC group compared to the control group, which indicated that immune balance tilts towards healing and bone formation. CONCLUSION: The xenogenous implanted DFSCs can induce the N2 phenotype of neutrophils in the early stage, which can activate the innate immune mechanism of the host to promote periodontal tissue regeneration.
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Saco Dental , Neutrófilos , Células Madre , Animales , Saco Dental/citología , Saco Dental/metabolismo , Ratones , Neutrófilos/metabolismo , Células Madre/metabolismo , Células Madre/citología , Regeneración , Diferenciación Celular , Periodoncio , Fenotipo , Trasplante de Células Madre/métodos , HumanosRESUMEN
Altruistic punishment is key to establishing cooperation and maintaining social order, yet its developmental trends across cultures remain unclear. Using computational reinforcement learning models, we provided the first evidence of how social feedback dynamically influences group-biased altruistic punishment across cultures and the lifespan. Study 1 (n = 371) found that Chinese participants exhibited higher learning rates than Americans when socially incentivized to punish unfair allocations. Additionally, Chinese adults showed slower learning and less exploration when punishing ingroups than outgroups, a pattern absent in American counterparts, potentially reflecting a tendency towards ingroup favoritism that may contribute to reinforcing collectivist values. Study 2 (n = 430, aged 12-52) further showed that such ingroup favoritism develops with age. Chinese participants' learning rates for ingroup punishment decreased from adolescence into adulthood, while outgroup rates stayed constant, implying a process of cultural learning. Our findings highlight cultural and age-related variations in altruistic punishment learning, with implications for social reinforcement learning and culturally sensitive educational practices promoting fairness and altruism.
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Altruismo , Castigo , Humanos , Castigo/psicología , Adulto , Masculino , Adolescente , Adulto Joven , Femenino , Persona de Mediana Edad , Niño , Refuerzo en Psicología , Estados Unidos , China , Comparación Transcultural , Biología Computacional , Aprendizaje/fisiologíaRESUMEN
Primary cilia are crucial for neurogenesis, and cilium-related genes are involved in the closure of neural tubes. Inositol polyphosphate-5-phosphatase (Inpp5e) was enriched in primary cilia and closely related to the occurrence of neural tube defects (NTDs). However, the role of Inpp5e in the development of NTDs is not well-known. To investigate whether Inpp5e gene is associated with the neural tube closure, we established a mouse model of NTDs by 5-fluorouracil (5-FU) exposure at gestational day 7.5 (GD7.5). The Inpp5e knockdown (Inpp5e-/-) mouse embryonic stem cells (mESCs) were produced by CRISPR/Cas9 system. The expressions of Inpp5e and other cilium-related genes including intraflagellar transport 80 (Ift80), McKusick-Kaufman syndrome (Mkks), and Kirsten rat sarcoma viral oncogene homolog (Kras) were determined, utilizing quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot, PCR array, and immunofluorescence staining. The result showed that the incidence of NTDs was 37.10% (23 NTDs/62 total embryos) and significantly higher than that in the control group (P < 0.001). The neuroepithelial cells of neural tubes were obviously disarranged in NTD embryos. The mRNA and protein levels of Inpp5e, Ift80, Mkks, and Kras were significantly decreased in NTD embryonic brain tissues, compared to the control (P < 0.05). Knockdown of the Inpp5e (Inpp5e-/-) reduced the expressions of Ift80, Mkks, and Kras in mESCs. Furthermore, the levels of α-tubulin were significantly reduced in NTD embryonic neural tissue and Inpp5e-/- mESCs. These results suggested that maternal 5-FU exposure inhibited the expression of Inpp5e, which resulted in the downregulation of cilium-related genes (Ift80, Mkks, and Kras), leading to the impairment of primary cilium development, and ultimately disrupted the neural tube closure.
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Cilios , Fluorouracilo , Defectos del Tubo Neural , Animales , Fluorouracilo/farmacología , Fluorouracilo/toxicidad , Cilios/metabolismo , Cilios/efectos de los fármacos , Defectos del Tubo Neural/genética , Defectos del Tubo Neural/inducido químicamente , Femenino , Ratones , Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/metabolismo , Embarazo , Células Madre Embrionarias de Ratones/metabolismo , Células Madre Embrionarias de Ratones/efectos de los fármacosRESUMEN
OBJECTIVE: Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist, is an anesthetic and sedative agent and has been reported to confer neuroprotective effects after cerebral hypoxic ischemia (CHI). This study was undertaken to elucidate the mechanisms by which microRNA (miR)-148a-3p is involved in the neuroprotective effect of DEX on hypoxic-ischemic brain damage in neonatal rats. METHODS: Neonatal rats were exposed to CHI conditions, a miR-148a-3p inhibitor, and DEX. Hippocampal astrocytes were isolated to construct an oxygen-glucose deprivation (OGD) model. qRT-PCR and western blot were utilized to inspect miR-148a-3p, STAT1, STAT3, JMJD3, cleaved-Caspase-1, ASC, NLRP3, GSDMD, and GSDMD-N expression in rats and astrocytes. TUNEL staining was employed to measure astrocyte apoptosis rate, immunofluorescence to inspect cleaved-Caspase-1 and ASC levels, and ELISA to determine IL-1ß and IL-18 expression. The target genes of miR-148a-3p were predicted using online software and verified by a dual-luciferase reporter gene assay. RESULTS: A prominent increase in astrocyte apoptosis rate and the expression of pyroptosis- and inflammation-related factors were found in rats with CHI and OGD-treated astrocytes. DEX suppressed astrocyte apoptosis rate and decreased expression of pyroptosis- and inflammation-related factors. Knockdown of miR-148a-3p facilitated astrocyte pyroptosis, indicating that DEX exerted its protective effect by upregulating miR-148a-3p. miR-148a-3p negatively mediated STAT to inactivate JMJD3. Overexpression of STAT1 and STAT3 facilitated pyroptosis in astrocytes, which was negated by the overexpression of miR-148a-3p. CONCLUSION: DEX inhibited hippocampal astrocyte pyroptosis by upregulating miR-148a-3p to inactivate the STAT/JMJD3 axis, thereby alleviating cerebral damage in neonatal rats with CHI.
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Dexmedetomidina , Hipoxia-Isquemia Encefálica , MicroARNs , Ratas , Animales , Piroptosis , MicroARNs/genética , Animales Recién Nacidos , Astrocitos/metabolismo , Apoptosis/genética , Hipoxia , Caspasa 1/metabolismo , Glucosa , Isquemia , Hipocampo/metabolismo , InflamaciónRESUMEN
Neural tube defects (NTDs) are complex congenital malformations resulting from failure of neural tube closure during embryogenesis, which is affected by the interaction of genetic and environmental factors. It is well known that folate deficiency increases the incidence of NTDs; however, the underlying mechanism remains unclear. Folate deficiency not only causes DNA hypomethylation, but also blocks the synthesis of 2'-deoxythymidine-5'-monophosphate (dTMP) and increases uracil misincorporation, resulting in genomic instabilities such as base mismatch, DNA breakage, and even chromosome aberration. DNA repair pathways are essential for ensuring normal DNA synthesis, genomic stability and integrity during embryonic neural development. Genomic instability or lack of DNA repair has been implicated in risk of development of NTDs. Here, we reviewed the relationship between folate deficiency, DNA repair pathways and NTDs so as to reveal the role and significance of DNA repair system in the pathogenesis of NTDs and better understand the pathogenesis of NTDs.
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Deficiencia de Ácido Fólico , Defectos del Tubo Neural , Humanos , Ácido Fólico/metabolismo , Defectos del Tubo Neural/genética , Deficiencia de Ácido Fólico/metabolismo , Reparación del ADN/genética , ADN , Inestabilidad GenómicaRESUMEN
Chemotherapeutic agents such as methotrexate (MTX), raltitrexed (RTX), 5-fluorouracil (5-FU), hydroxyurea (HU), and retinoic acid (RA), and valproic acid (VPA), an antiepileptic drug, all can cause malformations in the developing central nervous system (CNS), such as neural tube defects (NTDs). However, the common pathogenic mechanisms remain unclear. This study aimed to explore the mechanisms of NTDs caused by MTX, RTX, 5-FU, HU, RA, and VPA (MRFHRV), based on network pharmacology and molecular biology experiments. The MRFHRV targets were integrated with disease targets, to find the potential molecules related to MRFHRV-induced NTDs. Protein-protein interaction analysis and molecular docking were performed to analyze these common targets. Utilizing the kyoto encyclopedia of genes and genomes (KEGG) signaling pathways, we analyzed and searched the possible causative pathogenic mechanisms by crucial targets and the signaling pathway. Results showed that MRFHRV induced NTDs through several key targets (including TP53, MAPK1, HSP90AA1, ESR1, GRB2, HDAC1, EGFR, PIK3CA, RXRA, and FYN) and multiple signaling pathways such as PI3K/Akt pathway, suggesting that abnormal proliferation and differentiation could be critical pathogenic contributors in NTDs induced by MRFHRV. These results were further validated by CCK8 assay in mouse embryonic stem cells and GFAP staining in embryonic brain tissue. This study indicated that chemotherapeutic and antiepileptic agents induced NTDs might through predicted targets TP53, MAPK1, GRB2, HDAC1, EGFR, PIK3CA, RXRA, and FYN and multiple signaling pathways. More caution was required for the clinical administration for women with childbearing potential and pregnant.
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Antineoplásicos , Defectos del Tubo Neural , Animales , Femenino , Ratones , Embarazo , Anticonvulsivantes/efectos adversos , Fosfatidilinositol 3-Quinasa Clase I , Receptores ErbB , Fluorouracilo/efectos adversos , Hidroxiurea/efectos adversos , Simulación del Acoplamiento Molecular , Farmacología en Red , Defectos del Tubo Neural/inducido químicamente , Fosfatidilinositol 3-Quinasas , Tretinoina/efectos adversos , Ácido Valproico/efectos adversos , Metotrexato/efectos adversos , Antineoplásicos/efectos adversosRESUMEN
Despite the fast development of various energy harvesting and storage devices, their judicious integration into efficient, autonomous, and sustainable wearable systems has not been widely explored. Here, we introduce the concept and design principles of e-textile microgrids by demonstrating a multi-module bioenergy microgrid system. Unlike earlier hybrid wearable systems, the presented e-textile microgrid relies solely on human activity to work synergistically, harvesting biochemical and biomechanical energy using sweat-based biofuel cells and triboelectric generators, and regulating the harvested energy via supercapacitors for high-power output. Through energy budgeting, the e-textile system can efficiently power liquid crystal displays continuously or a sweat sensor-electrochromic display system in pulsed sessions, with half the booting time and triple the runtime in a 10-min exercise session. Implementing "compatible form factors, commensurate performance, and complementary functionality" design principles, the flexible, textile-based bioenergy microgrid offers attractive prospects for the design and operation of efficient, sustainable, and autonomous wearable systems.
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Bioingeniería/instrumentación , Ingeniería Biomédica/instrumentación , Textiles , Dispositivos Electrónicos Vestibles , Fuentes de Energía Bioeléctrica , Fenómenos Biomecánicos , Técnicas Biosensibles/instrumentación , Humanos , SudorRESUMEN
Smoking seriously affects oral health and causes a variety of oral diseases. Numerous clinical data show that smoking significantly increases the risk of periodontitis, and the duration and amount of smoking are positively correlated with the severity of periodontitis. In fact, smoking creates an environment conducive to the colonization of periodontopathogens, which affects the process of periodontitis. Since subgingival plaque which harbors periodontopathogens is the initiation factor of periodontitis, it is critical to study the impact of smoking on subgingival microbiota for understanding the relationship between smoking and periodontitis. Continuous advances have been made on the understanding of effects of smoking on subgingival plaque and the development of periodontitis. Smoking is observed to enhance the pathogenicity of periodontopathogens, especially the red complex microorganisms, via promoting their colonization and infection, and regulating the expression and function of multiple virulence factors. Furthermore, smoking has a negative impact on periodontal microecological homeostasis, which is reflected in the decrease of commensal bacteria and the increase of periodontopathogens, as well as the changes in the interaction between periodontopathogens and their commensal microbes in subgingival biofilm, thus influencing the pathogenicity of the subgingival plaque. In summary, the mechanism of smoking on subgingival plaque microorganisms represented by the red complex and its effect on the periodontal microecology still need to be further explored. The relevant research results are of great significance for guiding the periodontal clinical treatment of smoking population. This review summarizes the effects and relevant mechanisms of smoking on subgingival plaque and the development of periodontitis.
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INTRODUCTION: Intraoperative radiation therapy is an emerging option for adjuvant therapy for early stage breast cancer, although it is not currently considered standard of care in the United States. We applied time-driven activity-based costing to compare two alternative methods of breast intraoperative radiation therapy, including treatment similar to the techniques employed in the TARGIT-A clinical trial and a novel version with CT-guidance and high-dose-rate (HRD) brachytherapy. METHODS AND MATERIALS: Process maps were created to describe the steps required to deliver intraoperative radiation therapy for early stage breast cancer at each institution. The components of intraoperative radiation therapy included personnel, equipment, and consumable supplies. The capacity cost rate was determined for each resource. Based on this, the delivery costs were calculated for each regimen. For comparison across centers, we did not account for indirect facilities costs and interinstitutional differences in personnel salaries. RESULTS: The CT-guided, HRD form of intraoperative radiation therapy costs more to deliver ($4,126.21) than the conventional method studied in the TARGIT-A trial ($1,070.45). The cost of the brachytherapy balloon applicator ($2,750) was the primary driver of the estimated differences in costs. Consumable supplies were the largest contributor to the brachytherapy-based approach, whereas personnel costs were the largest contributor to costs of the standard form of intraoperative radiation therapy. CONCLUSIONS: When compared with the more established method of intraoperative radiation therapy using a portable superficial photon unit, the delivery of treatment with CT guidance and HDR brachytherapy is associated with substantially higher costs. The excess costs are driven primarily by the cost of the disposable brachytherapy balloon applicator and, to a lesser extent, additional personnel costs. Future work should include evaluation of a less expensive brachytherapy applicator to increase the anticipated value of brachytherapy-based intraoperative radiation therapy.
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Braquiterapia/economía , Neoplasias de la Mama/radioterapia , Costos de la Atención en Salud/estadística & datos numéricos , Braquiterapia/instrumentación , Braquiterapia/métodos , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Costos y Análisis de Costo , Equipos Desechables/economía , Femenino , Personal de Salud/economía , Humanos , Periodo Intraoperatorio , Persona de Mediana Edad , Estadificación de Neoplasias , Radiología Intervencionista/economía , Radioterapia Adyuvante/economía , Radioterapia Adyuvante/métodos , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Oviductus ranae is an animal-based traditional Chinese material widely used as tonics in China for hundreds of years. Various bioactive components are present in OR including proteins, amino acids, steroids, fatty acids, phospholipids, nucleosides, vitamins, hydantoins, and mineral elements. These constituents exert a myriad of biological functions such as immunomodulatory, antioxidant, antifatigue, antiaging, estrogen-like, hepatoprotective, hypolipidemic, antiosteoporotic, antidepressant, antitumor, antitussive, expectorant, anti-inflammatory, and antiasthmatic activities. Unlike other traditional Chinese crude drugs recorded in Chinese Pharmacopoeia, OR is seldom prescribed as medicine but often consumed as nutraceuticals to optimize health. In this review, the traditional uses, bioactive constituents, biological functions, and safety properties of OR as functional foods in China were summarized and discussed. It is expected that this review will provide useful information for anyone who is interested in OR.
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Alimentos Funcionales , Materia Medica , Medicina Tradicional China/métodos , China , HumanosRESUMEN
The complete mitochondrial genome sequence of the holoparasitic isopod Gyge ovalis (Shiino, 1939) has been determined. The mitogenome is 14,268 bp in length and contains 34 genes: 13 protein-coding genes, two ribosomal RNA, 19 tRNA and a control region. Three tRNA genes (trnE, trnI and trnS1) are missing. Most of the tRNA genes show secondary structures which derive from the usual cloverleaf pattern except for trnC which is characterised by the loss of the DHU-arm. Compared to the isopod ground pattern and Eurydice pulchra Leach, 1815 (suborder Cymothoida Wägele, 1989), the genome of G. ovalis shows few differences, with changes only around the control region. However, the genome of G. ovalis is very different from that of non-cymothoidan isopods and reveals that the gene order evolution in isopods is less conservative compared to other crustaceans. Phylogenic trees were constructed using maxiumum likelihood and Bayesian inference analyses based on 13 protein-coding genes. The results do not support the placement of G. ovalis with E. pulchra and Bathynomus sp. in the same suborder; rather, G. ovalis appears to have a closer relationship to Ligia oceanica (Linnaeus, 1767), but this result suggests a need for more data and further analysis. Nevertheless, these results cast doubt that Epicaridea Latreille, 1825 can be placed as an infraorder within the suborder Cymothoida, and Epicaridea appears to also deserve subordinal rank. Further development of robust phylogenetic relationships across Isopoda Latreille, 1817 will require more genetic data from a greater diversity of taxa belonging to all isopod suborders.
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Genoma Mitocondrial/genética , Isópodos/genética , Animales , Isópodos/clasificación , Filogenia , Especificidad de la EspecieRESUMEN
Hyperimmunoglobulin E syndromes (HIES) are rare primary immunodeficiency diseases characterized by markedly elevated serum immunoglobulin (Ig) E, recurrent pneumonia, and chronic eczema. To date, information about pediatric HIES is limited. We aimed to evaluate the spectrum of clinical and immunological features in pediatric patients with HIES in China.We retrospectively reviewed the cases of 4 pediatric patients with HIES followed at the Guangzhou Women and Children's Medical Center from May 2013 to September 2017. We analyzed clinical presentation, laboratory data, immunological evaluations, imagenological characteristics, treatment, response to therapy, genetic and bronchoalveolar lavage fluid (BALF) findings, and prognosis.The common clinical features of the patients were recurrent respiratory and mucocutaneous infections and eczematoid skin lesions. In 3 of 4 patients, BALF and transbronchial lung biopsy (TBLB) demonstrated fungal pneumonia with organisms including invasive Aspergillus and Penicillium marneffei. Elevated serum IgG and IgM were detected in 3 and 2 cases, respectively, while CD4+ T and CD19+ B cells were slightly reduced in only 1 patient. Nitroblue tetrazolium tests (NBTs) were normal in all patients, and reduced natural killer cell counts were identified in 3 patients. A novel missense mutation in exon 17 (c.1593A>T, p.K531N) was identified in the signal transducer and activator of transcription 3 (STAT3) gene that has not been reported previously. One patient had 3 homozygous nonsynonymous variations of the complement receptor 2 (CR2) gene distributed in exons 10 (c.1916G>A, p.S639N) and 11 (c.1987T>C, p.S663P and c.2012G>A, p.R671H) with high frequency.This case series suggests that fungi are important respiratory pathogens in children with HIES and should be considered in cases of pneumonia in this population. The NIH scoring system does not allow diagnostic certainty, particularly in infants, because some of the common manifestations of HIES may not develop until the patient matures. Pulmonary complications must be identified in the early stage of the disease to treat them effectively. In addition, we report a mutation in STAT3 that has not been identified previously.
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Síndrome de Job , Adolescente , Niño , Preescolar , China , Eccema/inmunología , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Síndrome de Job/genética , Síndrome de Job/inmunología , Síndrome de Job/microbiología , Enfermedades Pulmonares Fúngicas/inmunología , Enfermedades Pulmonares Fúngicas/microbiología , Masculino , Neumonía/inmunología , Neumonía/microbiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Inhaled corticosteroids (ICSs) for treating asthma are controversial because of their negative effects on the growth of asthmatic children and without clearly defined withdrawal strategy. A 2-year ICS step-down and withdrawal strategy has been developed for asthmatic children receiving 3-year subcutaneous immunotherapy (SCIT). METHODS: Eleven children were included into the SCIT group and 13 children into the ICS group. ICSs were discontinued when children met the following criteria: requiring only 1 puffper day, with good control, for at least 6 months; having a forced expiratory volume in 1 second (FEV1)/forced vital capacity ≥80%; and SCIT discontinued for ≥24 months. The main endpoints were the results of both the childhood asthma control test (C-CAT) and the methacholine bronchial provocation test. RESULTS: In the SCIT group, all the 11 children had ICS discontinued, with one child developed asthma attack after pneumonia and received ICS again after completion of SCIT. In the ICS group, five children discontinued ICS and developed asthma attacks later and received ICS again; the other eight children developed severe symptoms during ICS step-down. Thus, the discontinuation of ICS was only achieved in the SCIT group. The dose of methacholine that caused a decrease of 20% in FEV1 continued to improve after discontinuation of ICS for the SCIT group and presented better results than the ICS group (P=0.050). After completion of SCIT, the C-CAT had improved significantly after 30 months of treatment compared with the ICS group (P<0.05). CONCLUSIONS: In the present study, we developed a 2-year step-down and withdrawal strategy from ICSs strategy for allergic asthma children receiving SCIT; the strategy was efficacious and safe.
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Corticoesteroides/administración & dosificación , Asma/diagnóstico , Asma/tratamiento farmacológico , Inmunoterapia/métodos , Privación de Tratamiento , Administración por Inhalación , Corticoesteroides/efectos adversos , Niño , Preescolar , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/administración & dosificación , Inyecciones Subcutáneas , Masculino , Seguridad del Paciente , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
Mycoplasma pneumoniae (MP) is a leading cause of community-acquired pneumonia in children and young adults. Although MP pneumonia is usually benign and self-limited, in some cases it can develop into life-threating refractory MP pneumonia (RMPP). However, the pathogenesis of RMPP is poorly understood. The identification and characterization of proteins related to RMPP could provide a proof of principle to facilitate appropriate diagnostic and therapeutic strategies for treating paients with MP. In this study, we used a quantitative proteomic technique (iTRAQ) to analyze MP-related proteins in serum samples from 5 patients with RMPP, 5 patients with non-refractory MP pneumonia (NRMPP), and 5 healthy children. Functional classification, sub-cellular localization, and protein interaction network analysis were carried out based on protein annotation through evolutionary relationship (PANTHER) and Cytoscape analysis. A total of 260 differentially expressed proteins were identified in the RMPP and NRMPP groups. Compared to the control group, the NRMPP and RMPP groups showed 134 (70 up-regulated and 64 down-regulated) and 126 (63 up-regulated and 63 down-regulated) differentially expressed proteins, respectively. The complex functional classification and protein interaction network of the identified proteins reflected the complex pathogenesis of RMPP. Our study provides the first comprehensive proteome map of RMPP-related proteins from MP pneumonia. These profiles may be useful as part of a diagnostic panel, and the identified proteins provide new insights into the pathological mechanisms underlying RMPP.
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Interacciones Huésped-Patógeno , Mycoplasma pneumoniae/crecimiento & desarrollo , Neumonía por Mycoplasma/patología , Proteoma/análisis , Suero/química , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Mapas de Interacción de Proteínas , Proteómica/métodosRESUMEN
BACKGROUND: To establish the feasibility of the dosimetric compliance criteria of the RTOG 1308 trial through testing against Intensity Modulation Radiation Therapy (IMRT) and Passive Scattering Proton Therapy (PSPT) plans. METHODS: Twenty-six lung IMRT and 26 proton PSPT plans were included in the study. Dose Volume Histograms (DVHs) for targets and normal structures were analyzed. The quality of IMRT plans was assessed using a knowledge-based engineering tool. RESULTS: Most of the RTOG 1308 dosimetric criteria were achieved. The deviation unacceptable rates were less than 10 % for most criteria; however, a deviation unacceptable rate of more than 20 % was computed for the planning target volume minimum dose compliance criterion. Dose parameters for the target volume were very close for the IMRT and PSPT plans. However, the PSPT plans led to lower dose values for normal structures. The dose parameters in which PSPT plans resulted in lower values than IMRT plans were: lung V5Gy (%) (34.4 in PSPT and 47.2 in IMRT); maximum spinal cord dose (31.7 Gy in PSPT and 43.5 Gy in IMRT); heart V5Gy (%) (19 in PSPT and 47 in IMRT); heart V30Gy (%) (11 in PSPT and 19 in IMRT); heart V45Gy (%) (7.8 in PSPT and 12.1 in IMRT); heart V50% (Gy) (7.1 in PSPT and 9.8 in IMRT) and mean heart dose (7.7 Gy in PSPT and 14.9 Gy in IMRT). CONCLUSIONS: The revised RTOG 1308 dosimetric compliance criteria are feasible and achievable.
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Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Quimioradioterapia/métodos , Neoplasias Pulmonares/radioterapia , Fotones , Radiometría/métodos , Radioterapia de Intensidad Modulada/métodos , Estudios de Factibilidad , Humanos , Terapia de Protones/métodos , Garantía de la Calidad de Atención de Salud , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
Transmission of Imaging and Data (TRIAD) is a standard-based system built by the American College of Radiology to provide the seamless exchange of images and data for accreditation of clinical trials and registries. Scripts of structures' names validation profiles created in TRIAD are used in the automated submission process. It is essential for users to understand the logistics of these scripts for successful submission of radiation therapy cases with less iteration.
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Garantía de la Calidad de Atención de Salud/métodos , Exactitud de los Datos , Humanos , National Cancer Institute (U.S.) , Dosis de Radiación , Estados UnidosRESUMEN
Radiotherapy clinical-trial quality assurance is a crucial yet challenging process. This note presents a tool that automatically extracts dose/volume statistics for determining dosimetry compliance review with improved efficiency and accuracy. A major objective of this study is to develop an automated solution for clinical-trial radiotherapy dosimetry review.
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OBJECTIVE: To analyze the clinical and imagenological characteristics of acute Exogenous lipoid pneumonia (ELP), explore its risk factors, and assess the potential role of multiple bronchoalveolar lavages (BALs) and steroid therapy in the treatment of children with acute ELP. METHODS: Between May 2011 and July 2014, 33 pediatric patients with pneumonia caused by aspiration of oil-based substances were admitted to the Guangzhou Women and Children's Medical Center, Guangdong, China. Data on the demographics of these patients, as well as that on clinical presentations, imagenological characteristics, history of ingestion, laboratory observations, treatment protocol, response to therapy, BAL findings, and treatment outcomes were collected. RESULTS: The study group consisted of 23 boys (69.7 %) and 10 girls (30.3 %), with ages ranging from 4 mo to 4 y. They were admitted to the hospital 2 h to 13 d after ingesting the oil-based substance. By the time of admission, most patients presented with respiratory distress and other symptoms, including tachypnea (n = 21), cough (n = 25), mild fever (n = 18), progressive dyspnea (n = 12), and pneumorrhagia (n = 5); six patients received mechanical ventilation because of complicated respiratory distress syndrome. The most common laboratory observations were leukocytosis (25 of 33, 75.8 %), neutrophilia (23 of 33, 69.7 %), and anemia (8 of 33, 24.2 %). Serum biochemical examination showed elevated sedimentation rates (24 of 33, 72.7 %), lactate dehydrogenase levels (18 of 33, 54.5 %), and C-reactive protein levels (17 of 33, 51.5 %). The most common finding on computed tomography (CT) scans was areas of consolidation. Within the follow-up duration of 2 wk to 6 mo, all patients with clinical symptoms of ELP experienced remission, and none died. The CT scans of most of the cases were normal by 1 to 3 mo, except for two patients who showed complete improvement 6 mo after treatment. CONCLUSIONS: It was found that multiple BALs combined with steroid therapy result in significant improvement of clinical, radiologic, and laboratory parameters in children with acute ELP. Further, some traditional practices may predispose children to ELP, even in the absence of underlying risk factors. Finally, pneumorrhagia and acute respiratory distress syndrome may be the main complications of acute ELP in children.
Asunto(s)
Neumonía Lipoidea , Lavado Broncoalveolar , Preescolar , China , Tos , Femenino , Humanos , Lactante , Masculino , Neumonía Lipoidea/patología , Neumonía Lipoidea/fisiopatología , Tomografía Computarizada por Rayos XRESUMEN
The risk of local recurrence (LR), distant metastases (DM) and overall survival (OS) of locally advanced rectal cancer after preoperative chemoradiation can be estimated by prediction models and visualized using nomograms, which have been trained and validated in European clinical trial populations. Data of 277 consecutive locally advanced rectal adenocarcinoma patients treated with preoperative chemoradiation and surgery from Shanghai Cancer Center, were retrospectively collected and used for external validation. Concordance index (C-index) and calibration curves were used to assess the performance of the previously developed prediction models in this routine clinical validation population. The C-index for the published prediction models was 0.72 ± 0.079, 0.75 ± 0.043 and 0.72 ± 0.089 in predicting 2-year LR, DM and OS in the Chinese population, respectively. Kaplan-Meier curves indicated good discriminating performance regarding LR, but could not convincingly discriminate a low-risk and medium-risk group for distant control and OS. Calibration curves showed a trend of underestimation of local and distant control, as well as OS in the observed data compared with the estimates predicted by the model. In conclusion, we externally validated three models for predicting 2-year LR, DM and OS of locally advanced rectal cancer patients who underwent preoperative chemoradiation and curative surgery with good discrimination in a single Chinese cohort. However, the model overestimated the local control rate compared to observations in the clinical cohort. Validation in other clinical cohorts and optimization of the prediction model, perhaps by including additional prognostic factors, may enhance model validity and its applicability for personalized treatment of locally advanced rectal cancer.