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1.
Plant Cell Environ ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39222055

RESUMO

Pentatricopeptide repeat (PPR) gene family constitutes one of the largest gene families in plants, which mainly participate in RNA editing and RNA splicing of organellar RNAs, thereby affecting the organellar development. Recently, some evidence elucidated the important roles of PPR proteins in the albino process of plant leaves. However, the functions of PPR genes in the woody mangrove species have not been investigated. In this study, using a typical true mangrove Kandelia obovata, we systematically identified 298 PPR genes and characterized their general features and physicochemical properties, including evolutionary relationships, the subcellular localization, PPR motif type, the number of introns and PPR motifs, and isoelectric point, and so forth. Furthermore, we combined genome-wide association studies (GWAS) and transcriptome analysis to identify the genetic architecture and potential PPR genes associated with propagule leaves colour variations of K. obovata. As a result, we prioritized 16 PPR genes related to the albino phenotype using different strategies, including differentially expressed genes analysis and genetic diversity analysis. Further analysis discovered two genes of interest, namely Maker00002998 (PLS-type) and Maker00003187 (P-type), which were differentially expressed genes and causal genes detected by GWAS analysis. Moreover, we successfully predicted downstream target chloroplast genes (rps14, rpoC1 and rpoC2) bound by Maker00002998 PPR proteins. The experimental verification of RNA editing sites of rps14, rpoC1, and rpoC2 in our previous study and the verification of interaction between Maker00002998 and rps14 transcript using in vitro RNA pull-down assays revealed that Maker00002998 PPR protein might be involved in the post-transcriptional process of chloroplast genes. Our result provides new insights into the roles of PPR genes in the albinism mechanism of K. obovata propagule leaves.

2.
BMC Infect Dis ; 24(1): 745, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075343

RESUMO

BACKGROUND: Data on pyogenic liver abscess (PLA) of children in China have been limited. We aimed to summarize the clinical feather, microbiological characteristics, management, and outcome of PLA in children. METHOD: We retrospectively reviewed PLA cases from January 2008 to June 2023 at Beijing Children's Hospital. Clinical characteristics, pathogens and management were analyzed. RESULTS: We diagnosed 57 PLA patients in our center. The median onset age was 4.5 years and the male-to-female ratio was 1.6:1. The median diagnostic time was nine days and the median length of stay was 22 days. Twenty-eight patients (49.1%) had predisposing factors, around 71.4% of the patients had malignant hematology and primary immunodeficiency disease. Patients with underlying factors were more likely to have extrahepatic organ involvement (p = 0.024), anemia (p < 0.001), single abscess (p = 0.042), unilateral involvement (p = 0.039), and small size of the abscess (p = 0.008). Twenty-four patients (42.1%) had extrahepatic organ involvement. Pathogens were identified in 17 patients (29.8%), the most common pathogens were Klebsiella pneumoniae and Staphylococcus aureus. The positive rate of metagenomic next-generation sequencing (mNGS) was 87.5% (7/8). On multivariable analysis, the extrahepatic organ involved (p = 0.029) and hepatomegaly (p = 0.025) were two independent factors associated with poor outcomes. CONCLUSIONS: PLA is usually seen in children with predisposing factors. Malignant hematology and primary immunodeficiency disease were the most common underlying diseases. Extrahepatic organ involvement and hepatomegaly are associated with poor prognosis. Increased use of mNGS could be beneficial for identifying pathogens.


Assuntos
Abscesso Hepático Piogênico , Humanos , Abscesso Hepático Piogênico/microbiologia , Abscesso Hepático Piogênico/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Pré-Escolar , Criança , Lactente , Pequim/epidemiologia , Adolescente , Klebsiella pneumoniae/isolamento & purificação , Antibacterianos/uso terapêutico , Fatores de Risco , Staphylococcus aureus/isolamento & purificação
3.
Med Sci Monit ; 30: e942687, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38439525

RESUMO

BACKGROUND Sleep disorders are a common disease faced by people today and can lead to fatigue, lack of concentration, impaired memory, and even death. In recent years, the development of brain stimulation techniques has provided a new perspective for the treatment of sleep disorders. However, there is a lack of bibliometric analyses related to sleep disorders and brain stimulation techniques. Therefore, this study analyzed the application status and trend of brain stimulation technology in sleep disorder research. MATERIAL AND METHODS Articles and reviews published between 1999 and 2023 were retrieved from the Web of Science. CiteSpace was used to visually analyze the publications, countries, institutions, journals, authors, references, and keywords. RESULTS A total of 459 publications were obtained. The number of studies was shown to be on a general upward trend. The country with the largest number of publications was the United States; UDICE-French Research Universities had the highest number of publications; Neurology had the highest citation frequency; 90% of the top 10 references cited were from Journal Citation Reports Q1; Brigo was the author with the highest number of publications; and the most frequent keywords were "transcranial magnetic stimulation", "deep brain stimulation", and "Parkinson disease". CONCLUSIONS Our study used CiteSpace software to analyze 459 studies published since 1999 on brain stimulation techniques for the treatment of sleep disorders, revealing research trends and the current state of the field. Our results will help researchers to understand the existing research quickly and provide direction for future research.


Assuntos
Bibliometria , Transtornos do Sono-Vigília , Humanos , Fadiga , Transtornos do Sono-Vigília/terapia , Tecnologia , Encéfalo
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(5): 481-485, 2024 May 15.
Artigo em Zh | MEDLINE | ID: mdl-38802908

RESUMO

OBJECTIVES: To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation (PMV) due to different primary diseases. METHODS: A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022. According to the primary disease, they were divided into respiratory disease (RD) group, central nervous system (CNS) group, neuromuscular disease (NMD) group, and other disease group. The four groups were compared in terms of general information, treatment, and outcome. RESULTS: There were significant differences among the four groups in age, body weight, Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score, Pediatric Risk of Mortality III (PRISM Ⅲ) score, analgesic and sedative treatment, nutrition supply, rehabilitation treatment, tracheotomy, successful ventilator weaning, and outcomes (P<0.05). Compared with the RD group, the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment, and the CNS group had a significantly higher proportion of children receiving tracheotomy (P<0.008). Compared with the other disease group, the CNS group and the NMD group had significantly lower PELOD-2 and PRISM III scores, and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged (P<0.008). CONCLUSIONS: There are differences in clinical characteristics among children receiving PMV due to different etiologies. Most children in the RD group have a younger age, and children in the CNS group have a relatively good prognosis.


Assuntos
Doenças Neuromusculares , Respiração Artificial , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pré-Escolar , Lactente , Doenças Neuromusculares/terapia , Doenças Neuromusculares/etiologia , Criança , Doenças do Sistema Nervoso Central/etiologia , Doenças do Sistema Nervoso Central/terapia , Doenças Respiratórias/terapia , Doenças Respiratórias/etiologia
5.
Lupus ; 32(4): 500-507, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36748829

RESUMO

OBJECTIVE: To accelerate the onset of systemic lupus erythematosus in C57BL/6 mice by injecting cadmium chloride nanoemulsion and shorten the traditional modeling time. METHODS: Pristane cadmium chloride nanoemulsion was prepared, and 66 C57BL/6 mice were randomly divided into four groups. The pristane group was intraperitoneally injected with 0.6 mL of pristane blank nanoemulsion, the model group was injected with 0.6 mL of pristane cadmium chloride nanoemulsion, the Cadmium chloride control group was injected with 0.6 mL of cadmium chloride nanoemulsion, and the control group was injected with the same amount of 0.9% sodium chloride solution. Urine protein content, anti-dsDNA antibody content, Th1 cell/Th2 cell ratio, and kidney staining were detected in each group. RESULTS: The model group began to develop disease in the 4th week, the anti-dsDNA antibody level reached 566.71 ± 1.44 ng/L, and the proteinuria reached 245.38 ± 30.54 ng/mL. The model group showed an onset at least 5 weeks earlier than that in the pristane group. There was no significant difference in anti-dsDNA antibody content between Cadmium chloride control group and blank group. At the 12th week, the Th1/Th2 cell ratio in the model group significantly decreased, and the pathological changes in the kidneys were consistent with the typical manifestations of lupus in mouse models. CONCLUSION: These results suggest that cadmium chloride promotes earlier onset of pristane-induced systemic lupus erythematosus in a C57BL/6 mouse model.


Assuntos
Lúpus Eritematoso Sistêmico , Camundongos , Animais , Cloreto de Cádmio/toxicidade , Camundongos Endogâmicos C57BL , Terpenos/efeitos adversos , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C
6.
Plant Cell Rep ; 42(9): 1473-1485, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37516984

RESUMO

KEY MESSAGE: This study provided important insights into the genetic architecture of variations in A. thaliana leaf ionome in a cell-type-specific manner. The functional interpretation of traits associated variants by expression quantitative trait loci (eQTL) analysis is usually performed in bulk tissue samples. While the regulation of gene expression is context-dependent, such as cell-type-specific manner. In this study, we estimated cell-type abundances from 728 bulk tissue samples using single-cell RNA-sequencing dataset, and performed cis-eQTL mapping to identify cell-type-interaction eQTL (cis-eQTLs(ci)) in A. thaliana. Also, we performed Genome-wide association studies (GWAS) analyses for 999 accessions to identify the genetic basis of variations in A. thaliana leaf ionome. As a result, a total of 5,664 unique eQTL genes and 15,038 unique cis-eQTLs(ci) were significant. The majority (62.83%) of cis-eQTLs(ci) were cell-type-specific eQTLs. Using colocalization, we uncovered one interested gene AT2G25590 in Phloem cell, encoding a kind of plant Tudor-like protein with possible chromatin-associated functions, which colocalized with the most significant cis-eQTL(ci) of a Mo-related locus (Chr2:10,908,806:A:C; P = 3.27 × 10-27). Furthermore, we prioritized eight target genes associated with AT2G25590, which were previously reported in regulating the concentration of Mo element in A. thaliana. This study revealed the genetic regulation of ionomic variations and provided a foundation for further studies on molecular mechanisms of genetic variants controlling the A. thaliana ionome.


Assuntos
Arabidopsis , Locos de Características Quantitativas , Arabidopsis/genética , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética
7.
Aging Male ; 23(5): 841-846, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31058560

RESUMO

BACKGROUND AND OBJECTIVES: Evidence has supported obesity as a risk factor for both benign prostate hyperplasia (BPH) and hypogonadism. In this paper, we performed a retrospective study and discussed the prevalence of testosterone deficiency (TD) and its relationship to body mass index (BMI) in aging Chinese men with BPH who have surgical intervention. MATERIAL AND METHODS: We reviewed the clinical data by age, BMI, medical history, serum prostate-specific antigen (PSA) levels, serum total testosterone (TT) levels, biochemical analysis, and transrectal ultrasound. BMI and other variables were considered to be independent variables in an effort to evaluate any potential associations between these factors and TD status using non-adjusted and multivariate-adjusted regression models. RESULTS: Of the 795 BPH participants, 27.2% (216) patients had TD. After adjusting for all potential covariates, there was a similar J-shaped relationship between BMI and TD, with an inflection point of 19.2 kg/m2. The effect sizes and the confidence intervals on the left and right sides of this inflection point were 0.6 (0.4-1.0) (p = .043) and 1.2 (1.1-1.3) (p < .001), respectively. CONCLUSION: Nearly one-third of the aging Chinese BPH patients had TD in this study. The association between BMI and TD is not simple. A J-shaped curve correlation was detected. BMI was positively correlated with TD when it was over 19.2 kg/m2 and inversely correlated with TD when it was below 19.2 kg/m2. Long-term prospective studies are needed to confirm these findings.


Assuntos
Hiperplasia Prostática , Envelhecimento , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Humanos , Masculino , Hiperplasia Prostática/complicações , Estudos Retrospectivos , Testosterona
8.
Andrologia ; 52(11): e13763, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32829482

RESUMO

Acute urinary retention (AUR) is one of the progressive manifestations of benign prostatic hyperplasia (BPH). This cross-sectional study was conducted to analyse the possible association between serum interleukin 8 (sIL-8) and AUR in BPH patients to provide evidence of sIL-8 as a potential biomarker for the prediction of AUR. The relationship between sIL-8 levels and AUR was evaluated by logistic regressions in 245 ageing Chinese men with BPH. The discriminant validity of sIL-8 and the optimal cut-off value were determined by a receiver operating characteristic curve. The levels of sIL-8 increased significantly in BPH patients with AUR (p < 0.001). The sIL-8 concentration was positively correlated with AUR in BPH patients (OR = 1.024, 95% CI: 1.009-1.040, p = 0.002). The correlation with AUR in the group with a high sIL-8 level (≥43.05 pg/ml) was significantly enhanced (OR = 8.853, 95% CI: 2.433-32.205, p = 0.001). The sIL-8 level correlated with AUR in Chinese BPH patients independently. As a possible predictor, sIL-8 may contribute to the screening of high-risk populations for AUR to create opportunities for the early effective interventions to improve prognosis and enhance the quality of life. Prospective studies are needed to support all these results.


Assuntos
Hiperplasia Prostática , Retenção Urinária , China/epidemiologia , Estudos Transversais , Humanos , Interleucina-8 , Masculino , Estudos Prospectivos , Hiperplasia Prostática/complicações , Qualidade de Vida , Retenção Urinária/etiologia
9.
FASEB J ; 27(11): 4332-42, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23024374

RESUMO

A "longevity " gene, sirtuin 1 (SIRT1), can attenuate age-dependent induction of left ventricular dysfunction. This study aimed to characterize the role of SIRT1 in the tolerance of aged heart to ischemic insults. Male C57BL/6 young (4-6 mo) and aged (24-26 mo) mice were used to determine the role of SIRT1 in myocardial ischemia/reperfusion (I/R) tolerance. SIRT1 localization was assessed by confocal microscopy. Immunoblotting was used to evaluate SIRT1 expression and translocation. The results demonstrated that SIRT1 is expressed predominantly as a sumoylated form in cardiomyocyte nuclei. Moreover, cardiac overexpression of desumoylase, sentrin-specific protease 2 (SENP2), significantly reduces nuclear sumoylated SIRT1 levels (P<0.05). Interestingly, I/R stress leads to desumoylation and translocation of nuclear SIRT1 into the cytoplasm in aged but not in young hearts. SIRT1 activity in ischemic young hearts was 3.2-fold higher than that seen in ischemic aged hearts, which suggests that aging causes impaired nucleocytoplasmic shuttling and activation of SIRT1 during ischemic stress. The infarct size in aged and Sirt1(+/-) knockout hearts was higher than that observed in young and Sirt1(+/+) WT littermate hearts, respectively (all P<0.05). SIRT1 agonist, SRT1720, reduced myocardial infarction in both aged and Sirt1(+/-) hearts. Therefore, impaired cardiac SIRT1 activity plays a critical role in the observed increase in susceptibility of the aged heart to I/R injury. SIRT1 agonist can restore this aging-related loss of cardioprotection.


Assuntos
Envelhecimento , Núcleo Celular/metabolismo , Coração/crescimento & desenvolvimento , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Sirtuína 1/metabolismo , Transporte Ativo do Núcleo Celular , Fatores Etários , Animais , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Citoplasma/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Transporte Proteico , Sirtuína 1/efeitos dos fármacos , Sirtuína 1/genética , Estresse Fisiológico , Sumoilação
10.
World J Gastrointest Surg ; 16(1): 6-12, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38328310

RESUMO

Gastric cancer (GC) is a prevalent malignant tumor within the digestive system, with over 40% of new cases and deaths related to GC globally occurring in China. Despite advancements in treatment modalities, such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents, the prognosis for GC remains poor. New targeted therapies and immunotherapies are currently under investigation, but no significant breakthroughs have been achieved. Studies have indicated that GC is a heterogeneous disease, encompassing multiple subtypes with distinct biological characteristics and roles. Consequently, personalized treatment based on clinical features, pathologic typing, and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer (PLGC). Current research has categorized GC into four subtypes: Epstein-Barr virus-positive, microsatellite instability, genome stability, and chromosome instability (CIN). Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas. Among these, ultrasensitive chromosomal aneuploidy detection (UCAD) can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology, in conjunction with bioinformatics analysis, to achieve qualitative and quantitative detection of chromosomal stability. This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

11.
Curr Pediatr Rev ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38778597

RESUMO

BACKGROUND: The COVID-19 global pandemic was caused by a novel coronavirus (SARS-CoV-2), which then became an endemic infection. COVID refers to the World Health Organization's coined acronym for coronavirus disease. CASE PRESENTATION: We have, herein, reported three cases of coronavirus diseases that could have been misdiagnosed as COVID-19. All of these families reported previous COVID-19 infection based on self-administered Rapid Antigen Testing (RAT) and completed a period of home isolation. In the current presentation, one child had an RSV-associated asthma attack, one had norovirus gastritis, and another had an infection with Campylobacter and E. coli. NL63, OC43, and 229E, respectively, were found by PCR in these patients. DISCUSSION: Seven human coronaviruses cause infectious diseases, including in children. Confusion and issues associated with coronavirus disease diagnosis by Polymerase Chain Reaction (PCR) testing and Rapid Antigen Test (RAT) may arise. Some RATs are Antigen Fluorescent Immunoassays (FIA) that target monoclonal antibodies for the detection of viral nucleocapsid protein. Others target the non-nucleocapsid proteins. False positivity is possible. False negativity is also possible if the specimen's antigen level is below the test's detection limit. RAT results usually remain positive for 6 to 7 days, but they may stay positive as long as 2 weeks. Stigmatization with the COVID-19 diagnosis may occur. The PCR test is a highly sensitive 'gold standard' for the detection of COVID-19, but it can also detect non-infectious individuals' fragmented non-infectious viral nucleic acids, and could be positive for a long period. An individual may be tested positive for a few weeks to months after the individual becomes non-infectious. CONCLUSION: The cases presented here had coronavirus diseases other than COVID-19. Coronavirus diseases can be caused by coronavirus variants other than SARS-CoV-2. Co-infections with other pathogens are present in these diseases. PCR testing of non-COVID-19 diseases may help in the accurate diagnosis of these ailments and respiratory co-infections.

12.
PLoS Genet ; 6(5): e1000932, 2010 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-20463879

RESUMO

Genome-wide association studies (GWAS) have demonstrated the ability to identify the strongest causal common variants in complex human diseases. However, to date, the massive data generated from GWAS have not been maximally explored to identify true associations that fail to meet the stringent level of association required to achieve genome-wide significance. Genetics of gene expression (GGE) studies have shown promise towards identifying DNA variations associated with disease and providing a path to functionally characterize findings from GWAS. Here, we present the first empiric study to systematically characterize the set of single nucleotide polymorphisms associated with expression (eSNPs) in liver, subcutaneous fat, and omental fat tissues, demonstrating these eSNPs are significantly more enriched for SNPs that associate with type 2 diabetes (T2D) in three large-scale GWAS than a matched set of randomly selected SNPs. This enrichment for T2D association increases as we restrict to eSNPs that correspond to genes comprising gene networks constructed from adipose gene expression data isolated from a mouse population segregating a T2D phenotype. Finally, by restricting to eSNPs corresponding to genes comprising an adipose subnetwork strongly predicted as causal for T2D, we dramatically increased the enrichment for SNPs associated with T2D and were able to identify a functionally related set of diabetes susceptibility genes. We identified and validated malic enzyme 1 (Me1) as a key regulator of this T2D subnetwork in mouse and provided support for the association of this gene to T2D in humans. This integration of eSNPs and networks provides a novel approach to identify disease susceptibility networks rather than the single SNPs or genes traditionally identified through GWAS, thereby extracting additional value from the wealth of data currently being generated by GWAS.


Assuntos
Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/genética , Expressão Gênica , Estudo de Associação Genômica Ampla , Fígado/metabolismo , Polimorfismo de Nucleotídeo Único , Animais , Estudos de Coortes , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
13.
Pediatr Pulmonol ; 58(7): 2017-2024, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37098833

RESUMO

BACKGROUND: With the increase in macrolide-resistant M. pneumoniae infections, off-label use is difficult to avoid. This study assessed the safety of moxifloxacin in pediatric patients with severe refractory M. pneumoniae pneumonia (SRMPP). METHODS: We retrospectively reviewed the medical records of children with SRMPP between January 2017 and November 2020 at Beijing Children's Hospital. They were divided into the moxifloxacin group and azithromycin group according to whether or not moxifloxacin was used. The clinical symptoms, radiographs of both knees, and cardiac ultrasounds of the children were collected after drug withdrawal for at least 1 year. A multidisciplinary team reviewed all adverse events and determined their relationship with moxifloxacin. RESULTS: A total of 52 children with SRMPP were included in this study (31 in the moxifloxacin group and 21 in the azithromycin group). In the moxifloxacin group, four patients had arthralgia, one had joint effusion, and seven had heart valve regurgitation. In the azithromycin group, three patients had arthralgia, one had claudication, and one had heart valve regurgitation; no obvious knee abnormalities were observed in the radiographs. No statistically significant differences in clinical symptoms or imaging findings were found between the groups. As for the adverse events, 11 patients in moxifloxacin group were deemed to be doubtfully related and one possibly related to moxifloxacin; in the azithromycin group, four patients were regarded to be doubtfully related to azithromycin and one not related. CONCLUSION: Moxifloxacin was well tolerated and safe for treating SRMPP in children.


Assuntos
Azitromicina , Pneumonia por Mycoplasma , Criança , Humanos , Azitromicina/efeitos adversos , Moxifloxacina/uso terapêutico , Mycoplasma pneumoniae , Estudos Retrospectivos , Pneumonia por Mycoplasma/diagnóstico por imagem , Pneumonia por Mycoplasma/tratamento farmacológico , Antibacterianos/efeitos adversos , Farmacorresistência Bacteriana
14.
J Immunol Res ; 2023: 8942415, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37026113

RESUMO

Background: Systemic lupus erythematosus (SLE) is characterized by poor regulation of the immune response leading to chronic inflammation and multiple organ dysfunction. Glucocorticoid (GC) is currently one of the main treatments. However, a high dose or prolonged use of GC may result in glucocorticoid-induced osteoporosis (GIOP). Jiedu Quyu Ziyin decoction (JP) is effective in treating SLE and previous clinical studies have proved that JP can prevent and treat SLE steroid osteoporosis (SLE-GIOP). We aim to examine JPs main mechanism on SLE-GIOP through network pharmacology and molecular docking. Methods: TCMSP and TCMID databases were used to screen potential active compounds and targets of JP. The SLE-GIOP targets are collected from GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. R software was used to obtain the cross-targets of JP and SLE-GIOP and to perform GO and KEGG enrichment analysis. Cytoscape software was used to make the Chinese Medicines-Active Ingredient-Intersection Targets network diagram. STRING database construct protein-protein interaction network and obtain the core targets. Auto Dock Tools and Pymol software were used for docking. Results: Fifty eight targets overlapped between JP and SLE-GIOP were suggested as potential targets of JP in the treatment of SLE-GIOP. Network topology analysis identified five core targets. GO enrichment analysis was obtained 1,968 items, and the top 10 biological process, closeness centrality, and molecular function were displayed. A total of 154 signaling pathways were obtained by KEGG enrichment analysis, and the top 30 signaling pathways were displayed. JP was well bound by MAPK1, TP53, and MYC according to the molecular docking results. Conclusion: We investigated the potential targets and signaling pathways of JP against SLE-GIOP in this study. It shows that JP is most likely to achieve the purpose of treating SLE-GIOP by promoting the proliferation and differentiation of osteoblasts. A solid theoretical foundation will be provided for the future study of clinical and experimental topics.


Assuntos
Medicamentos de Ervas Chinesas , Lúpus Eritematoso Sistêmico , Osteoporose , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Glucocorticoides , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Osteoporose/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
15.
Biochem Biophys Res Commun ; 421(3): 501-7, 2012 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-22521889

RESUMO

A series of inhibitors of d-amino acid oxidase (DAAO) are specific in blocking chronic pain, including formalin-induced tonic pain, neuropathic pain and bone cancer pain. This study used RNA interference technology to further validate the notion that spinal DAAO mediates formalin-induced pain. To target DAAO, a siRNA/DAAO formulated in polyetherimide (PEI) complexation and a shRNA/DAAO (shDAAO, with the same sequence as siRNA/DAAO after intracellular processing) expressed in recombinant adenoviral vectors were designed. The siRNA/DAAO was effective in blocking DAAO expression in NRK-52E rat kidney tubule epithelial cells, compared to the nonspecific oligonucleotides. Furthermore, multiple-daily intrathecal injections of both siRNA/DAAO and Ad-shDAAO for 7 days significantly inhibited spinal DAAO expression by 50-80% as measured by real-time quantitative PCR and Western blot, and blocked spinal DAAO enzymatic activity by approximately 60%. Meanwhile, both siRNA/DAAO and Ad-shDAAO prevented formalin-induced tonic phase pain by approximately 60%. Multiple-daily intrathecal injections of siRNA/DAAO and Ad-shDAAO also blocked more than 30% spinal expression of GFAP, a biomarker for the activation of astrocytes. These results further suggest that down-regulation of spinal DAAO expression and enzymatic activity leads to analgesia with its mechanism potentially related to activation of astrocytes in the spinal cord.


Assuntos
Analgesia/métodos , D-Aminoácido Oxidase/antagonistas & inibidores , Dor/fisiopatologia , Medula Espinal/enzimologia , Animais , Astrócitos/enzimologia , Astrócitos/fisiologia , D-Aminoácido Oxidase/genética , Regulação para Baixo , Células Epiteliais/enzimologia , Formaldeído/farmacologia , Injeções Espinhais , Túbulos Renais/enzimologia , Masculino , Dor/induzido quimicamente , Dor/enzimologia , Interferência de RNA , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Medula Espinal/fisiopatologia , Transgenes
16.
J Assist Reprod Genet ; 29(12): 1435-42, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23090745

RESUMO

BACKGROUND: Identification of a non-invasive technique to assess embryo implantation potential in assisted reproduction would greatly increase success rates and lead more efficiently to single embryo transfer. Early studies suggested metabonomic analysis of spent culture media could improve embryo selection. The goal of this study is to assess if embryo implantation can be predicted based on proton nuclear magnetic resonance ((1)H NMR) profiles of spent embryo culture media from patients undergoing transfer of multiple embryos on cycle day 3. METHOD: We conducted a retrospective study in an academic assisted reproduction technology (ART) program and analyzed the data in a university research center. Two hundred twenty-eight spent culture media samples originating from 108 patients were individually analyzed. Specifically, five distinct sets (1 to 5) of different types of spent media samples (volume ~14 µL) from embryos that resulted in clinical pregnancy (positive heart rate at 6 weeks gestation) (n (1) = 29; n (2) = 19; n (3) = 9; n (4) = 12; n (5) = 33; n (total) = 102) and from embryos that did not implant (n (1) = 28; n (2) = 29; n (3) = 18; n (4) = 15; n (5) = 36; n (total) = 126) were collected on day 3 of embryo growth. The media samples were profiled using (1)H NMR spectroscopy, and the NMR profiles of sets 1 to 5 were subject to standard uni- and multi-variate data analyses in order to evaluate potential correlation of profiles with implantation success. RESULTS: For set 1 of the media samples, a borderline class separation of NMR profiles was obtained by use of principal component analysis (PCA) and logistic regression. This tentative class separation could not be repeated and validated in any of the other media sets 2 to 5. CONCLUSIONS: Despite the rigorous technical approach, (1)H NMR based profiling of spent culture media cannot predict success of implantation for day 3 human embryos.


Assuntos
Meios de Cultivo Condicionados/química , Implantação do Embrião , Feto/diagnóstico por imagem , Prognóstico , Transferência de Embrião Único , Adulto , Transferência Embrionária , Desenvolvimento Embrionário , Feminino , Fertilização in vitro , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Gravidez , Taxa de Gravidez , Prótons , Radiografia , Técnicas de Reprodução Assistida , Estudos Retrospectivos
17.
World J Pediatr ; 18(3): 214-221, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35150398

RESUMO

BACKGROUND: Early post-traumatic seizures (EPTS) refer to epileptic seizures occurring within one week after brain injury. This study aimed to define the risk factors of EPTS and the protective factors that could prevent its occurrence. METHODS: This is a single-center retrospective study in the PICU, Beijing Children's Hospital. Patients diagnosed with traumatic brain injury (TBI), admitted with and without EPTS between January 2016 and December 2020 were included in the study. RESULTS: We included 108 patients diagnosed with TBI. The overall EPTS incidence was 33.98% (35/108). The correlation between EPTS and depressed fractures is positive (P = 0.023). Positive correlations between EPTS and intracranial hemorrhage and subarachnoid hemorrhage had been established (P = 0.011and P = 0.004, respectively). The detection rates of EPTS in the electroencephalogram (EEG) monitoring was 80.00%. There was a significant difference in the EEG monitoring rate between the two groups (P = 0.041). Forty-one (37.86%, 41/108) post-neurosurgical patients were treated with prophylactic antiepileptic drugs (AEDs), and eight (19.51%, 8/41) still had seizures. No statistical significance was noted between the two groups in terms of prophylactic AEDs use (P = 0.519). Logistic regression analysis revealed that open craniocerebral injury and fever on admission were risk factors for EPTS, whereas, surgical intervention and use of hypertonic saline were associated with not developing EPTS. CONCLUSIONS: Breakthrough EPTS occurred after severe TBI in 33.98% of pediatric cases in our cohort. This is a higher seizure incidence than that reported previously. Patients with fever on admission and open craniocerebral injuries are more likely to develop EPTS.


Assuntos
Lesões Encefálicas Traumáticas , Epilepsia Pós-Traumática , Epilepsia , Anticonvulsivantes/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/epidemiologia , Criança , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Epilepsia/etiologia , Epilepsia Pós-Traumática/epidemiologia , Epilepsia Pós-Traumática/etiologia , Epilepsia Pós-Traumática/prevenção & controle , Febre , Humanos , Estudos Retrospectivos , Convulsões/diagnóstico
18.
World J Pediatr ; 18(11): 734-745, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35737181

RESUMO

BACKGROUND: We explored the differences in baseline characteristics, pathogens, complications, outcomes, and risk factors between children with hospital-acquired septic shock (HASS) and community-acquired septic shock (CASS) in the pediatric intensive care unit (PICU). METHODS: This retrospective study enrolled children with septic shock at the PICU of Beijing Children's Hospital from January 1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided into the HASS and CASS group. Logistic regression analysis was used to identify risk factors for mortality. RESULTS: A total of 298 children were enrolled. Among them, 65.9% (n = 91) of HASS patients had hematologic/oncologic diseases, mainly with Gram-negative bacterial bloodstream infections (47.3%). Additionally, 67.7% (n = 207) of CASS patients had no obvious underlying disease, and most experienced Gram-positive bacterial infections (30.9%) of the respiratory or central nervous system. The 28-day mortality was 62.6% and 32.7% in the HASS and CASS groups, respectively (P < 0.001). Platelet [odds ratio (OR) = 0.996, 95% confidence interval (CI) = 0.992-1.000, P = 0.028], positive pathogen detection (OR = 3.557, 95% CI = 1.307-9.684, P = 0.013), and multiple organ dysfunction syndrome (OR = 10.953, 95% CI = 1.974-60.775, P = 0.006) were risk factors for 28-day mortality in HASS patients. Lactate (OR = 1.104, 95% CI = 1.022-1.192, P = 0.012) and mechanical ventilation (OR = 8.114, 95% CI = 1.806-36.465, P = 0.006) were risk factors for 28-day mortality in patients with CASS. CONCLUSIONS: The underlying diseases, pathogens, complications, prognosis, and mortality rates varied widely between the HASS and CASS groups. The predictors of 28-day mortality were different between HASS and CASS pediatric patients with septic shock.


Assuntos
Choque Séptico , Criança , Hospitais , Humanos , Ácido Láctico , Ácido Penicilânico/análogos & derivados , Prognóstico , Estudos Retrospectivos , Choque Séptico/diagnóstico , Choque Séptico/terapia
19.
Front Pharmacol ; 13: 1021661, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467038

RESUMO

Background: Pneumonia, caused by infection or other factors, seriously endangers the health of children. Meropenem is an effective broad-spectrum antibiotic using in the treatment of infectious diseases. In the therapy of pneumonia, meropenem is mostly employed for the treatment of moderate to severe pneumonia. Previously, we established a population pharmacokinetics (PPK) model for meropenem in pediatric severe infection and simulated the control rate of the time during which the free plasma concentration of meropenem exceeds the minimum inhibitory concentration (MIC) is 70% of the dosing interval (70% fT > MIC). Therefore, we plan to conduct a multicenter randomized controlled trial (RCT) to compare the efficacy and safety between conventional regimen and model regimen for meropenem in pediatric severe pneumonia. Methods: One hundred patients (aged 3 months to 15 years) will be recruited in this RCT. They will be assigned randomly (at a 1:1 ratio) to a conventional treatment group (20 mg/kg, q8h, with 0.5-1 h infusion) and a model treatment group (20 mg/kg, q8 h, with 4 h infusion). The primary outcome will be 70% fT > MIC. Secondary outcomes will be the prevalence of meropenem therapy failure, duration of antibiotic therapy, changes in levels of inflammatory indicators, changes in imaging examination results, and prevalence of adverse events. Ethical approval of our clinical trial has been granted by the ethics committee of Beijing Children's Hospital ([2022]-E-133-Y). This trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2200061207). Discussion: Based on our previous PPK data, we have designed this RCT. It is hoped that it will promote rational use of antibacterial drugs in children suffering from severe pneumonia. Clinical Trial Registration: http://www.chictr.org.cn identifier, ChiCTR2200061207.

20.
Polymers (Basel) ; 14(9)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35566886

RESUMO

Currently, the provisional stenting technique is the gold standard in revascularization of lesions located in the left main (LM) bifurcation. The benefit of the routine kissing balloon technique (KBI) in bifurcation lesions is still debated, particularly following the single stent treatment. We compared the latest-generation drug-eluting stent (DES) with no side branch (SB) dilatation "keep it open" technique (KIO) vs. KBI technique vs. bifurcation dedicated drug-eluting stent (BD-DES) implantation. In vitro testing was performed under a static condition in bifurcation silicone vessel models. All the devices were implanted in accordance with the manufacturers' recommendations. As a result, computational fluid dynamics (CFD) analysis demonstrated a statistically higher area of high shear rate in the KIO group when compared to KBI. Likewise, the maximal shear rate was higher in number in the KIO group. Floating strut count based on the OCT imaging was significantly higher in KIO than in KBI and BD-DES. Furthermore, according to OTC analysis, the thrombus area was numerically higher in both KIO and KBI than in the BD-DES. Scanning electron microscopy (SEM) analysis shows the highest degree of strut coating damage in the KBI group. This model demonstrated significant differences in CFD analysis at SB ostia with and without KBI optimization in the LM setting. The adoption of KBI was related to a meaningful reduction of flow disturbances in conventional DES and achieved results similar to BD-DES.

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