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1.
Cell ; 150(2): 351-65, 2012 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-22817897

RESUMEN

Wnt signaling is involved in self-renewal and maintenance of hematopoietic stem cells (HSCs); however, the particular role of noncanonical Wnt signaling in regulating HSCs in vivo is largely unknown. Here, we show Flamingo (Fmi) and Frizzled (Fz) 8, members of noncanonical Wnt signaling, both express in and functionally maintain quiescent long-term HSCs. Fmi regulates Fz8 distribution at the interface between HSCs and N-cadherin(+) osteoblasts (N-cad(+)OBs that enrich osteoprogenitors) in the niche. We further found that N-cad(+)OBs predominantly express noncanonical Wnt ligands and inhibitors of canonical Wnt signaling under homeostasis. Under stress, noncanonical Wnt signaling is attenuated and canonical Wnt signaling is enhanced in activation of HSCs. Mechanistically, noncanonical Wnt signaling mediated by Fz8 suppresses the Ca(2+)-NFAT- IFNγ pathway, directly or indirectly through the CDC42-CK1α complex and also antagonizes canonical Wnt signaling in HSCs. Taken together, our findings demonstrate that noncanonical Wnt signaling maintains quiescent long-term HSCs through Fmi and Fz8 interaction in the niche.


Asunto(s)
Cadherinas/metabolismo , Células Madre Hematopoyéticas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Nicho de Células Madre , Vía de Señalización Wnt , Animales , Cadherinas/genética , Femenino , Células Madre Hematopoyéticas/citología , Humanos , Interferón gamma/metabolismo , Ratones , Ratones Transgénicos , Factores de Transcripción NFATC/metabolismo , Receptores Acoplados a Proteínas G/genética
2.
Pharmacol Rev ; 76(1): 49-89, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37696583

RESUMEN

Systemic diseases of liver origin (SDLO) are complex diseases in multiple organ systems, such as cardiovascular, musculoskeletal, endocrine, renal, respiratory, and sensory organ systems, caused by irregular liver metabolism and production of functional factors. Examples of such diseases discussed in this article include primary hyperoxaluria, familial hypercholesterolemia, acute hepatic porphyria, hereditary transthyretin amyloidosis, hemophilia, atherosclerotic cardiovascular diseases, α-1 antitrypsin deficiency-associated liver disease, and complement-mediated diseases. Nucleic acid therapeutics use nucleic acids and related compounds as therapeutic agents to alter gene expression for therapeutic purposes. The two most promising, fastest-growing classes of nucleic acid therapeutics are antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs). For each listed SDLO disease, this article discusses epidemiology, symptoms, genetic causes, current treatment options, and advantages and disadvantages of nucleic acid therapeutics by either ASO or siRNA drugs approved or under development. Furthermore, challenges and future perspectives on adverse drug reactions and toxicity of ASO and siRNA drugs for the treatment of SDLO diseases are also discussed. In summary, this review article will highlight the clinical advantages of nucleic acid therapeutics in targeting the liver for the treatment of SDLO diseases. SIGNIFICANCE STATEMENT: Systemic diseases of liver origin (SDLO) contain rare and common complex diseases caused by irregular functions of the liver. Nucleic acid therapeutics have shown promising clinical advantages to treat SDLO. This article aims to provide the most updated information on targeting the liver with antisense oligonucleotides and small interfering RNA drugs. The generated knowledge may stimulate further investigations in this growing field of new therapeutic entities for the treatment of SDLO, which currently have no or limited options for treatment.


Asunto(s)
Hepatopatías , Ácidos Nucleicos , Humanos , Ácidos Nucleicos/uso terapéutico , ARN Interferente Pequeño/uso terapéutico , Oligonucleótidos Antisentido/efectos adversos , Hepatopatías/tratamiento farmacológico
3.
Am J Pathol ; 194(2): 238-252, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37995836

RESUMEN

Substance P (SP) is a neuropeptide released by neurons and participates in various biological processes, including inflammation. M2 macrophages are major immune cells associated with type 2 inflammation in asthma. This study investigated the effect of SP on macrophage phenotype in pediatric asthma and the underpinning factors. Asthmatic children exhibited an increased level of SP, along with a higher proportion of M2 macrophages in their bronchoalveolar lavage fluid. Flow cytometry revealed that SP treatment enhanced the M2 polarization of 12-O-tetradecanoylphorbol 13-acetate-treated THP-1 cells (macrophages) in vitro. By contrast, the administration of a neutralizing antibody of SP reduced the M2 macrophage population, mitigated inflammatory cell infiltration in mouse lung tissues, and decreased the population of immune cells in the mouse bronchoalveolar lavage fluid. SP up-regulated the expression of STAT6, which, in turn, activated the transcription of lymphocyte cytosolic protein 2 (LCP2). The population of macrophages and allergic inflammatory responses in mice were reduced by STAT6 inhibition but restored by LCP2 overexpression. Collectively, the present study demonstrated that SP sustains M2 macrophage predominance and allergic inflammation in pediatric asthma by enhancing STAT6-dependent transcription activation of LCP2.


Asunto(s)
Asma , Sustancia P , Niño , Humanos , Ratones , Animales , Sustancia P/farmacología , Activación Transcripcional , Asma/metabolismo , Macrófagos/metabolismo , Inflamación/metabolismo , Linfocitos/metabolismo , Factor de Transcripción STAT6 , Activación de Macrófagos
4.
Cereb Cortex ; 34(4)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38602740

RESUMEN

This study aimed to investigate the moderating role of aerobic fitness on the effect of acute exercise on improving executive function from both behavioral and cerebral aspects. Thirty-four young individuals with motor skills were divided into high- and low-fitness groups based on their maximal oxygen uptake. Both groups completed 30 min of moderate-intensity aerobic exercise on a power bike. Executive function tests (Flanker, N-back, More-odd-shifting) were performed before and after exercise and functional near-infrared spectroscopy was used to monitor prefrontal cerebral blood flow changes during the tasks. The results indicated significant differences between the two groups regarding executive function. Participants with lower aerobic fitness performed better than their higher fitness counterparts in inhibitory control and working memory, but not in cognitive flexibility. This finding suggests that the aerobic fitness may moderate the extent of cognitive benefits gained from acute aerobic exercise. Furthermore, the neuroimaging data indicated negative activation in the frontopolar area and dorsolateral prefrontal cortex in response to three complex tasks. These findings underscore the importance of considering individual aerobic fitness when assessing the cognitive benefits of exercise and could have significant implications for tailoring fitness programs to enhance cognitive performance.


Asunto(s)
Función Ejecutiva , Ejercicio Físico , Humanos , Memoria a Corto Plazo , Circulación Cerebrovascular , Corteza Prefontal Dorsolateral
5.
Breast Cancer Res Treat ; 206(1): 45-56, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38616207

RESUMEN

PURPOSE: The significance of postmastectomy radiotherapy (PMRT) in breast cancer patients who initially have clinically node-positive (cN +) status but achieve downstaging to ypN0 following neoadjuvant chemotherapy (NAC) remains uncertain. This study aims to assess the impact of PMRT in this patient subset. METHODS: Patients were enrolled from West China Hospital, Sichuan University from 2008 to 2019. Overall survival (OS), Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and assessed with the log-rank test. The impact of PMRT was further analyzed by the Cox proportional hazards model. Propensity score matching (PSM) was performed to reduce the selection bias. RESULTS: Of the 333 eligible patients, 189 (56.8%) received PMRT, and 144 (43.2%) did not. At a median follow-up period of 71 months, the five-year LRFS, DMFS, BCSS, and OS rates were 99.1%, 93.4%, 96.4%, and 94.3% for the entire cohort, respectively. Additionally, the 5-year LRFS, DMFS, BCSS, and OS rates were 98.9%, 93.8%, 96.7%, and 94.5% with PMRT and 99.2%, 91.3%, 94.9%, and 92.0% without PMRT, respectively (all p-values not statistically significant). After multivariate analysis, PMRT was not a significant risk factor for any of the endpoints. When further stratified by stage, PMRT did not show any survival benefit for patients with stage II-III diseases. CONCLUSION: In the context of comprehensive treatments, PMRT might be exempted in ypN0 breast cancer patients. Further large-scale, randomized controlled studies are required to investigate the significance of PMRT in this patient subset.


Asunto(s)
Neoplasias de la Mama , Mastectomía , Terapia Neoadyuvante , Estadificación de Neoplasias , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Adulto , Anciano , Estudios Retrospectivos , Radioterapia Adyuvante/métodos , Quimioterapia Adyuvante/métodos , Metástasis Linfática , Recurrencia Local de Neoplasia/patología
6.
Mol Psychiatry ; 28(7): 3092-3103, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37117459

RESUMEN

Evidence suggests that neurometabolite alterations may be involved in the pathophysiology of autism spectrum disorders (ASDs). We performed a meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies to examine the neurometabolite levels in the brains of patients with ASD. A systematic search of PubMed and Web of Science identified 54 studies for the meta-analysis. A random-effects meta-analysis demonstrated that compared with the healthy controls, patients with ASD had lower N-acetyl-aspartate-containing compound (NAA) and choline-containing compound (Cho) levels and NAA/(creatine-containing compound) Cr ratios in the gray matter and lower NAA and glutamate + glutamine (Glx) levels in the white matter. Furthermore, NAA and gamma-aminobutyric acid (GABA) levels, NAA/Cr ratios, and GABA/Cr ratios were significantly decreased in the frontal cortex of patients with ASD, whereas glutamate (Glu) levels were increased in the prefrontal cortex. Additionally, low NAA levels and GABA/Cr ratios in the temporal cortex, low NAA levels and NAA/Cr ratios in the parietal and dorsolateral prefrontal cortices, and low NAA levels in the cerebellum and occipital cortex were observed in patients with ASD. Meta-regression analysis revealed that age was positively associated with effect size in studies analyzing the levels of gray matter NAA and white matter Glx. Taken together, these results provide strong clinical evidence that neurometabolite alterations in specific brain regions are associated with ASD and age is a confounding factor for certain neurometabolite levels in patients with ASD.


Asunto(s)
Trastorno del Espectro Autista , Humanos , Espectroscopía de Protones por Resonancia Magnética/métodos , Trastorno del Espectro Autista/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Ácido Glutámico , Ácido Aspártico , Colina , Ácido gamma-Aminobutírico
7.
J Org Chem ; 89(4): 2637-2648, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38277477

RESUMEN

A Cu/Pd-cocatalyzed 1,5-boroacylation of cyclopropyl-substituted ACPs with B2pin2 and acid chlorides has been developed. Using cyclopropyl-substituted ACPs as the starting material, a broad range of 1,5-boroacylated products with multiple functional groups was prepared in good yields with excellent regio- and stereoselectively. Both aromatic and aliphatic acid chlorides were tolerated in this reaction.

8.
Fish Shellfish Immunol ; 149: 109591, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38679344

RESUMEN

Toll-like receptors (TLRs) are one of the extensively studied pattern recognition receptors (PRRs) and play crucial roles in the immune responses of vertebrates and invertebrates. In this study, 14 TLR genes were identified from the genome-wide data of Octopus sinensis. Protein structural domain analysis showed that most TLR proteins had three main structural domains: extracellular leucine-rich repeats (LRR), transmembrane structural domains, and intracellular Toll/IL-1 receptor domain (TIR). The results of subcellular localization prediction showed that the TLRs of O. sinensis were mainly located on the plasma membrane. The results of quantitative real-time PCR (qPCR) showed that the detected TLR genes were differentially expressed in the hemolymph, white bodies, hepatopancreas, gills, gill heart, intestine, kidney, and salivary gland of O. sinensis. Furthermore, the present study investigated the expression changes of O. sinensis TLR genes in hemolymph, white bodies, gills, and hepatopancreas in different phases (6 h, 12 h, 24 h, 48 h) after stimulation with PGN, poly(I: C) and Vibrio parahaemolyticus. The expression of most of the TLR genes was upregulated at different time points after infection with pathogens or stimulation with PAMPs, a few genes were unchanged or even down-regulated, and many of the TLR genes were much higher after V. parahaemolyticus infection than after PGN and poly(I:C) stimulation. The results of this study contribute to a better understanding of the molecular immune mechanisms of O. sinensis TLRs genes in resistance to pathogen stimulation.


Asunto(s)
Regulación de la Expresión Génica , Inmunidad Innata , Octopodiformes , Receptores Toll-Like , Vibrio parahaemolyticus , Animales , Receptores Toll-Like/genética , Receptores Toll-Like/inmunología , Receptores Toll-Like/química , Vibrio parahaemolyticus/fisiología , Octopodiformes/genética , Octopodiformes/inmunología , Inmunidad Innata/genética , Regulación de la Expresión Génica/inmunología , Filogenia , Perfilación de la Expresión Génica/veterinaria , Poli I-C/farmacología , Peptidoglicano/farmacología , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/inmunología , Proteínas de Artrópodos/química , Moléculas de Patrón Molecular Asociado a Patógenos/farmacología
9.
Environ Sci Technol ; 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38344765

RESUMEN

Volatile sulfur compounds, such as dimethyl sulfide (DMS), carbonyl sulfide (OCS), and carbon disulfide (CS2), have significant implications for both atmospheric chemistry and climate change. Despite the crucial role of oceans in regulating their atmospheric budgets, our comprehension of their cycles in seawater remains insufficient. To address this gap, a field investigation was conducted in the western North Pacific to clarify the sources, sinks, and biogeochemical controls of these gases in two different marine environments, including relatively eutrophic Kuroshio-Oyashio extension (KOE) and oligotrophic North Pacific subtropical gyre. Our findings revealed higher concentrations of these gases in both seawater and the atmosphere in the KOE compared to the subtropical gyre. In the KOE, nutrient-rich upwelling stimulated rapid DMS biological production, while reduced seawater temperatures hindered the removal of OCS and CS2, leading to their accumulation. Furthermore, we have quantitatively evaluated the relative contribution of each pathway to the source and sink of DMS, OCS, and CS2 within the mixed layer and identified vertical exchange as a potential sink in most cases, transporting substantial amounts of these gases from the mixed layer to deeper waters. This research advances our understanding of sulfur gas source-sink dynamics in seawater, contributing to the assessment of their marine emissions and atmospheric budgets.

10.
Int Wound J ; 21(4): e14605, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38149500

RESUMEN

The objective of this study was to investigate the risk factors associated with surgical site infection (SSI) after percutaneous endoscopic lumbar discectomy (PELD) in patients with lumbar disc herniation (LDH). A retrospective analysis was performed on a cohort of 335 patients who underwent PELD between January 2016 and January 2023. Data were derived from the Hospital Information System (HIS), and a comprehensive statistical assessment was performed using IBM SPSS Statistics version 25.0. Both univariate and multivariate logistic regression analyses assessed a range of risk determinants, such as age, body mass index (BMI), comorbidities, laboratory test parameters and surgery-related variables. The incidence of SSI after PELD was 2.7% (9/335). Univariate analysis highlighted BMI, diabetes mellitus, long-term corticosteroid consumption, surgical time and cerebrospinal fluid leakage as significant predictors of SSI. Multivariate logistic regression identified BMI, diabetes mellitus, long-term corticosteroid consumption, surgical time and cerebrospinal fluid leakage as significant risk factors for SSI after PELD. High BMI, diabetes mellitus, long-term corticosteroid consumption, long surgical time and postoperative cerebrospinal fluid leakage are predisposing factors for SSI in patients undergoing PELD. Precise interventions focused on such risk components, including careful preoperative assessment and strategic postoperative care, are essential to reduce the incidence of SSI and improve surgical efficacy.


Asunto(s)
Diabetes Mellitus , Discectomía Percutánea , Desplazamiento del Disco Intervertebral , Humanos , Estudios Retrospectivos , Desplazamiento del Disco Intervertebral/epidemiología , Desplazamiento del Disco Intervertebral/etiología , Desplazamiento del Disco Intervertebral/cirugía , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/cirugía , Discectomía Percutánea/efectos adversos , Vértebras Lumbares/cirugía , Factores de Riesgo , Corticoesteroides , Pérdida de Líquido Cefalorraquídeo/etiología , Pérdida de Líquido Cefalorraquídeo/cirugía , Resultado del Tratamiento
11.
EMBO J ; 38(16): e101397, 2019 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-31290162

RESUMEN

NOD-like receptor (NLR) family CARD domain containing 3 (NLRC3), an intracellular member of NLR family, is a negative regulator of inflammatory signaling pathways in innate and adaptive immune cells. Previous reports have shown that NLRC3 is expressed in dendritic cells (DCs). However, the role of NLRC3 in DC activation and immunogenicity is unclear. In the present study, we find that NLRC3 attenuates the antigen-presenting function of DCs and their ability to activate and polarize CD4+ T cells into Th1 and Th17 subsets. Loss of NLRC3 promotes pathogenic Th1 and Th17 responses and enhanced experimental autoimmune encephalomyelitis (EAE) development. NLRC3 negatively regulates the antigen-presenting function of DCs via p38 signaling pathway. Vaccination with NLRC3-overexpressed DCs reduces EAE progression. Our findings support that NLRC3 serves as a potential target for treating adaptive immune responses driving multiple sclerosis and other autoimmune disorders.


Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Células Dendríticas/inmunología , Encefalomielitis Autoinmune Experimental/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Animales , Presentación de Antígeno , Autoinmunidad , Linfocitos T CD4-Positivos/trasplante , Polaridad Celular , Células Cultivadas , Células Dendríticas/citología , Encefalomielitis Autoinmune Experimental/terapia , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones , Transducción de Señal , Células TH1/citología , Células TH1/metabolismo , Células Th17/citología , Células Th17/metabolismo , Vacunación
12.
Drug Metab Dispos ; 51(6): 672-684, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36973001

RESUMEN

Significant interindividual and intraindividual variations on cytochrome P450 (CYP)-mediated drug metabolism exist in the general population globally. Genetic polymorphisms are one of the major contribution factors for interindividual variations, but epigenetic mechanisms mainly contribute to intraindividual variations, including DNA methylation, histone modifications, microRNAs, and long non-coding RNAs. The current review provides analysis of advanced knowledge in the last decade on contributions of epigenetic mechanisms to intraindividual variations on CYP-mediated drug metabolism in several situations, including (1) ontogeny, the developmental changes of CYP expression in individuals from neonates to adults; (2) increased activities of CYP enzymes induced by drug treatment; (3) increased activities of CYP enzymes in adult ages induced by drug treatment at neonate ages; and (4) decreased activities of CYP enzymes in individuals with drug-induced liver injury (DILI). Furthermore, current challenges, knowledge gaps, and future perspective of the epigenetic mechanisms in development of CYP pharmacoepigenetics are discussed. In conclusion, epigenetic mechanisms have been proven to contribute to intraindividual variations of drug metabolism mediated by CYP enzymes in age development, drug induction, and DILI conditions. The knowledge has helped understanding how intraindividual variation are generated. Future studies are needed to develop CYP-based pharmacoepigenetics to guide clinical applications for precision medicine with improved therapeutic efficacy and reduced risk of adverse drug reactions and toxicity. SIGNIFICANCE STATEMENT: Understanding epigenetic mechanisms in contribution to intraindividual variations of CYP-mediated drug metabolism may help to develop CYP-based pharmacoepigenetics for precision medicine to improve therapeutic efficacy and reduce adverse drug reactions and toxicity for drugs metabolized by CYP enzymes.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , MicroARNs , Recién Nacido , Humanos , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Epigénesis Genética/genética , MicroARNs/genética , MicroARNs/metabolismo , Inactivación Metabólica , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/genética
13.
Opt Lett ; 48(22): 5831-5834, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37966730

RESUMEN

We propose a scheme to realize a novel, to the best of our knowledge, scenario that the single-photon transport in a one-dimensional waveguide can be affected by the temperature. The scheme is composed by a waveguide-atom interacting structure linked to a thermal bath. The single-photon reflection (or transmission) coefficient can be controlled by adjusting the temperature of the thermal bath. This provides a thermal control of the single-photon transport. Moreover, the scheme provides an approach for implementing the optical thermometer, in which the temperature of the thermal bath is estimated by measuring the photonic transport. The thermometer can accurately measure the temperature in the low-temperature region.

14.
Opt Lett ; 48(3): 823-826, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36723598

RESUMEN

We investigate the heat conduction between two one-dimensional waveguides intermediated by a laser-driving atom. The laser provides the optical control of the heat conduction. The tunable asymmetric conduction of the heat against the temperature gradient is realized. Assisted by the modulated laser, the heat conduction from either waveguide to the other waveguide can be suppressed. The heat currents can be significantly amplified by the energy flow of the laser.

15.
BMC Cancer ; 23(1): 385, 2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37106444

RESUMEN

OBJECTIVE: A neural network method was employed to establish a dose prediction model for organs at risk (OAR) in patients with cervical cancer receiving brachytherapy using needle insertion. METHODS: A total of 218 CT-based needle-insertion brachytherapy fraction plans for loco-regionally advanced cervical cancer treatment were analyzed in 59 patients. The sub-organ of OAR was automatically generated by self-written MATLAB, and the volume of the sub-organ was read. Correlations between D2cm3 of each OAR and volume of each sub-organ-as well as high-risk clinical target volume for bladder, rectum, and sigmoid colon-were analyzed. We then established a neural network predictive model of D2cm3 of OAR using the matrix laboratory neural net. Of these plans, 70% were selected as the training set, 15% as the validation set, and 15% as the test set. The regression R value and mean squared error were subsequently used to evaluate the predictive model. RESULTS: The D2cm3/D90 of each OAR was related to volume of each respective sub-organ. The R values for bladder, rectum, and sigmoid colon in the training set for the predictive model were 0.80513, 0.93421, and 0.95978, respectively. The ∆D2cm3/D90 for bladder, rectum, and sigmoid colon in all sets was 0.052 ± 0.044, 0.040 ± 0.032, and 0.041 ± 0.037, respectively. The MSE for bladder, rectum, and sigmoid colon in the training set for the predictive model was 4.779 × 10-3, 1.967 × 10-3 and 1.574 × 10-3, respectively. CONCLUSION: The neural network method based on a dose-prediction model of OAR in brachytherapy using needle insertion was simple and reliable. In addition, it only addressed volumes of sub-organs to predict the dose of OAR, which we believe is worthy of further promotion and application.


Asunto(s)
Braquiterapia , Neoplasias del Cuello Uterino , Femenino , Humanos , Braquiterapia/efectos adversos , Braquiterapia/métodos , Órganos en Riesgo , Dosificación Radioterapéutica , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/etiología , Recto , Redes Neurales de la Computación , Planificación de la Radioterapia Asistida por Computador/métodos
16.
J Biomed Sci ; 30(1): 53, 2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37430371

RESUMEN

The liver is an immune organ that plays a vital role in the detection, capture, and clearance of pathogens and foreign antigens that invade the human body. During acute and chronic infections, the liver transforms from a tolerant to an active immune state. The defence mechanism of the liver mainly depends on a complicated network of intrahepatic and translocated immune cells and non-immune cells. Therefore, a comprehensive liver cell atlas in both healthy and diseased states is needed for new therapeutic target development and disease intervention improvement. With the development of high-throughput single-cell technology, we can now decipher heterogeneity, differentiation, and intercellular communication at the single-cell level in sophisticated organs and complicated diseases. In this concise review, we aimed to summarise the advancement of emerging high-throughput single-cell technologies and re-define our understanding of liver function towards infections, including hepatitis B virus, hepatitis C virus, Plasmodium, schistosomiasis, endotoxemia, and corona virus disease 2019 (COVID-19). We also unravel previously unknown pathogenic pathways and disease mechanisms for the development of new therapeutic targets. As high-throughput single-cell technologies mature, their integration into spatial transcriptomics, multiomics, and clinical data analysis will aid in patient stratification and in developing effective treatment plans for patients with or without liver injury due to infectious diseases.


Asunto(s)
COVID-19 , Transcriptoma , Humanos , COVID-19/genética , Hígado , Hepatocitos , Perfilación de la Expresión Génica
17.
Anesthesiology ; 139(3): 262-273, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37440205

RESUMEN

BACKGROUND: Individualized positive end-expiratory pressure (PEEP) guided by dynamic compliance improves oxygenation and reduces postoperative atelectasis in nonobese patients. The authors hypothesized that dynamic compliance-guided PEEP could also reduce postoperative atelectasis in patients undergoing bariatric surgery. METHODS: Patients scheduled to undergo laparoscopic bariatric surgery were eligible. Dynamic compliance-guided PEEP titration was conducted in all patients using a downward approach. A recruitment maneuver (PEEP from 10 to 25 cm H2O at 5-cm H2O step every 30 s, with 15-cm H2O driving pressure) was conducted both before and after the titration. Patients were then randomized (1:1) to undergo surgery under dynamic compliance-guided PEEP (PEEP with highest dynamic compliance plus 2 cm H2O) or PEEP of 8 cm H2O. The primary outcome was postoperative atelectasis, as assessed with computed tomography at 60 to 90 min after extubation, and expressed as percentage to total lung tissue volume. Secondary outcomes included Pao2/inspiratory oxygen fraction (Fio2) and postoperative pulmonary complications. RESULTS: Forty patients (mean ± SD; 28 ± 7 yr of age; 25 females; average body mass index, 41.0 ± 4.7 kg/m2) were enrolled. Median PEEP with highest dynamic compliance during titration was 15 cm H2O (interquartile range, 13 to 17; range, 8 to 19) in the entire sample of 40 patients. The primary outcome of postoperative atelectasis (available in 19 patients in each group) was 13.1 ± 5.3% and 9.5 ± 4.3% in the PEEP of 8 cm H2O and dynamic compliance-guided PEEP groups, respectively (intergroup difference, 3.7%; 95% CI, 0.5 to 6.8%; P = 0.025). Pao2/Fio2 at 1 h after pneumoperitoneum was higher in the dynamic compliance-guided PEEP group (397 vs. 337 mmHg; group difference, 60; 95% CI, 9 to 111; P = 0.017) but did not differ between the two groups 30 min after extubation (359 vs. 375 mmHg; group difference, -17; 95% CI, -53 to 21; P = 0.183). The incidence of postoperative pulmonary complications was 4 of 20 in both groups. CONCLUSIONS: Postoperative atelectasis was lower in patients undergoing laparoscopic bariatric surgery under dynamic compliance-guided PEEP versus PEEP of 8 cm H2O. Postoperative Pao2/Fio2 did not differ between the two groups.


Asunto(s)
Atelectasia Pulmonar , Síndrome de Dificultad Respiratoria , Femenino , Humanos , Respiración con Presión Positiva/métodos , Atelectasia Pulmonar/etiología , Atelectasia Pulmonar/prevención & control , Obesidad/complicaciones , Pulmón , Síndrome de Dificultad Respiratoria/complicaciones
18.
J Neurooncol ; 164(1): 117-125, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37474745

RESUMEN

PURPOSE: Chemotherapy is commonly used for treatment in children over three years old with high-risk medulloblastoma(MB). However, little is currently known about the therapeutic benefits and side effects of intrathecal methotrexate(MTX), warranting further research. METHODS: In this retrospective study, patients who received intrathecal MTX during chemotherapy were included in the MTX group (n = 32), and patients that only underwent cerebrospinal fluid (CSF) cytology analysis were assigned to the control group (n = 14). RESULTS: In the MTX group, 27(84.38%) patients had metastatic disease, 3(9.38%) had diffuse anaplasia, and 3(9.38%) had residual disease greater than 1.5 cm2. Molecular subgroup classification was available for 28(87.5%) patients. In the control group, 8(57.14%) patients had metastatic disease, 3(27.27%) had diffuse anaplasia, and 6(42.86%) had residual disease greater than 1.5 cm2. Molecular subgroup classification was available for 6(42.86%) patients. The 5-year progression-free survival was 70.99% and the 5-year overall survival was 72.99% for the MTX group, and the corresponding values were 41.67% and 50% for the control group, respectively. 6 (18.75%) patients in the MTX group with group 4 disease developed MTX-related acute leukoencephalopathy and one of them died. CONCLUSIONS: Our findings support the addition of intrathecal MTX during chemotherapy as the optimal management for children with group 3 and SHH high-risk MB. However, it is not recommended for group 4 MB patients, especially in resource-limited regions. TRIAL REGISTRATION NUMBER: Retrospective registered No.(2020 - 117).


Asunto(s)
Neoplasias Cerebelosas , Meduloblastoma , Niño , Humanos , Preescolar , Metotrexato/efectos adversos , Meduloblastoma/patología , Estudios Retrospectivos , Anaplasia/inducido químicamente , Anaplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Cerebelosas/patología
19.
Epidemiol Infect ; 151: e64, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-37009679

RESUMEN

The timely identification of the high-risk groups for nosocomial infections (NIs) plays a vital role in its prevention and control. Therefore, it is crucial to investigate whether the ABO blood group is a risk factor for NI. In this study, patients with NI and non-infection were matched by the propensity score matching method and a logistic regression model was used to analyse the matched datasets. The study found that patients with the B&AB blood group were susceptible to Escherichia coli (OR = 1.783, p = 0.039); the A blood group were susceptible to Staphylococcus aureus (OR = 2.539, p = 0.019) and Pseudomonas aeruginosa (OR = 5.724, p = 0.003); the A&AB blood group were susceptible to Pseudomonas aeruginosa (OR = 4.061, p = 0.008); the AB blood group were vulnerable to urinary tract infection (OR = 13.672, p = 0.019); the B blood group were susceptible to skin and soft tissue infection (OR = 2.418, p = 0.016); and the B&AB blood group were vulnerable to deep incision infection (OR = 4.243, p = 0.043). Summarily, the patient's blood group is vital for identifying high-risk groups for NIs and developing targeted prevention and control measures for NIs.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Infección Hospitalaria , Humanos , Infección Hospitalaria/epidemiología , Escherichia coli , Pseudomonas aeruginosa , Factores de Riesgo , Staphylococcus aureus
20.
Mol Breed ; 43(6): 44, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37313219

RESUMEN

Wheat stripe rust is one of the diseases that seriously affect wheat production worldwide. Breeding resistant cultivars is an effective way to control this disease. The wheat stripe rust resistance gene Yr62 has high-temperature adult-plant resistance (HTAP). In this study, PI 660,060, a single Yr62 gene line, was crossed with four Chinese wheat cultivars, LunXuan987 (LX987), Bainongaikang58 (AK58), ZhengMai9023 (ZM9023), and HanMai6172 (H6172). F1 seeds of four cross combinations were planted and self-crossed to develop the advance generations in the field. The seeds of each cross were mixed harvested and about 2400 to 3000 seeds were sown in each generation for F1 to F4 to maintain the maximum possible genotypes. Forty-five lines were selected and evaluated for resistance to stripe rust and agronomic traits, including plant height, number of grains per spike, and tiller number, in F5 and F6. Then, 33 lines with good agronomic traits and high disease resistance were developed to F9 generation. SSR markers Xgwm251 and Xgwm192 flank linked with the Yr62 were used to detect the presence of Yr62 in these 33 F9 lines. Of these, 22 lines were confirmed with the resistance gene Yr62. Finally, nine lines with good agronomic traits and disease resistance were successfully selected. The selected wheat lines in this study provide material support for the future breeding of wheat for stripe rust resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01393-1.

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