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1.
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
2.
Eur J Clin Microbiol Infect Dis ; 43(8): 1517-1531, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38842766

RESUMO

BACKGROUND: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited. PURPOSE: To gain a better understanding about GAS meningitis. METHODS: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized. RESULTS: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%. CONCLUSIONS: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death.


Assuntos
Meningites Bacterianas , Infecções Estreptocócicas , Streptococcus pyogenes , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Antibacterianos/uso terapêutico , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia , Meningites Bacterianas/mortalidade , Fatores de Risco , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/mortalidade
4.
BMJ Open ; 12(3): e049840, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35296470

RESUMO

OBJECTIVE: To date, there is no standard diagnostic practice to identify the underlying disease-causing mechanism for paediatric patients suffering from chronic fever without any specific diagnosis, which is one of the leading causes of death in paediatric patients. Therefore, we aimed this retrospective study to analyse medical records of paediatric patients with fever of unknown origin (FUO) to provide a preliminary basis for improving the diagnostic categories and facilitate the treatment outcomes. DESIGN: A retrospective study. SETTING: Beijing Children's Hospital. PARTICIPANTS: Clinical data were collected from 1288 children between 1 month and 18 years of age diagnosed with FUO at Beijing Children's Hospital between January 2010 and December 2017. INTERVENTIONS: According to the aetiological composition, age, duration of fever and laboratory examination results, the diagnostic strategies were analysed and formulated. PRIMARY AND SECONDARY OUTCOME MEASURES: The statistical analyses were carried out using SPSS V.24.0 platform along with the χ2 test and analysis of variance (p<0.05). RESULTS: The duration of fever ranged from 2 weeks to 2 years, with an average of 6 weeks. There were 656 cases (50.9%) of infectious diseases, 63 cases (4.9%) of non-infectious inflammatory diseases (NIIDs), 86 cases (6.7%) of neoplastic diseases, 343 cases (26.6%) caused by miscellaneous diseases and 140 cases (10.9%) were undiagnosed. With increasing age, the proportion of FUO from infectious diseases gradually decreased from 73.53% to 44.21%. NIID was more common in children over 3 years old, and neoplastic diseases mainly occurred from 1 to 6 years of age. Among miscellaneous diseases, the age distribution was mainly in school-aged children over 6 years. Respiratory tract infection was the most common cause of FUO in children, followed by bloodstream infections. Bacterial infection was the most common cause in children with less than 1 year old, while the virus was the main pathogen in children over 1 year old. CONCLUSIONS: The diagnosis of neoplastic diseases and miscellaneous diseases-related diseases still depends mainly on invasive examination. According to our clinical experience, the diagnostic process was formulated based on fever duration and the type of disease. This process can provide a guide for the diagnosis and treatment of paediatric FUO in the future.


Assuntos
Doenças Transmissíveis , Febre de Causa Desconhecida , Pequim/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Doenças Transmissíveis/diagnóstico , Febre de Causa Desconhecida/diagnóstico , Febre de Causa Desconhecida/epidemiologia , Febre de Causa Desconhecida/etiologia , Humanos , Lactente , Estudos Retrospectivos
5.
J Pediatric Infect Dis Soc ; 10(5): 635-640, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-33491083

RESUMO

BACKGROUND: Few data on recurrent bacterial meningitis (RBM) in children are available. Here, we estimated the frequency of RBM in children and investigated the predisposing conditions, etiology, and clinical characteristics of RBM in children. METHODS: Cases of RBM in the Beijing Children's Hospital medical record database between January 2006 and December 2019 were collected. RESULTS: In total, 1905 children with bacterial meningitis (BM) were documented in the Beijing Children's Hospital medical record database. A total of 43 patients had RBM. The rate of RBM in children was 2.3% (43/1905). Forty (93.0%) patients had predisposing conditions, including 15 (34.9%) cases of inner ear malformations, 5 (11.6%) cases of dermal sinus tracts, 9 (20.9%) cases of head injury, 5 (11.6%) cases of congenital cranial meningocele, 3 (7.0%) cases of congenital skull base defects, 3 (7.0%) cases of immunodeficiency, and other 3 (7.0%) cases of unknown reason. Among all the 121 BM episodes, a total of 64 episodes were etiologically confirmed BM and the other 57 episodes were probable BM. Streptococcus pneumoniae (n = 52) was accounted for 81.3% of confirmed BM episodes. Thirty-four of the 37 patients with congenital or acquired anatomical defects were available to follow up after surgeries, and all of them had no BM after surgeries. Three patients with antibody deficiencies got intravenous immunoglobulin therapy and they did not suffer BM anymore. CONCLUSIONS: RBM is rare in children. The majority of children with RBM had predisposing conditions including congenital/acquired anatomical defects and immunodeficiency. Interventions should be implemented to solve the underlying conditions to avoid RBM.


Assuntos
Síndromes de Imunodeficiência , Meningites Bacterianas , Criança , Hospitais Pediátricos , Humanos , Estudos Retrospectivos , Streptococcus pneumoniae
6.
Pediatr Infect Dis J ; 40(2): 109-115, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33044433

RESUMO

BACKGROUND: There are limit studies about pediatric brain abscess in China. The aim of this study was to analyze clinical characteristics and outcomes of pediatric brain abscess in recent years in China. METHODS: The clinical information of children with brain abscess hospitalized in Beijing Children's Hospital between January 1, 2007 and December 31, 2016 were retrospectively reviewed. RESULTS: Ninety-four children were enrolled in this study. A Streptococcus milleri group (13.8%) was identified as the most common causative organisms, followed by Staphylococcus aureus (6.4%). The overall mortality was 21.6%, with 50.0% of deaths happening in the first week after diagnosis. Long-term outcomes of 74 patients were assessed with Glasgow Outcome Scale-Extended Pediatric Reversion: 50 patients with a score of 1-2 (favorable outcome) and 24 patients with a score of 3-8 (unfavorable outcome). Patients with multiple abscesses (P = 0.029) and intraventricular rupture of brain abscess/hydrocephalus (P = 0.024) had higher risk of unfavorable outcomes. CONCLUSIONS: Brain abscess is a serious disease with high mortality in children; more aggressive treatments should be considered in the first week of diagnosis because of high risk of death, and for patients with multiple brain abscesses and intraventricular rupture of brain abscess/hydrocephalus because of their higher risk of unfavorable.


Assuntos
Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Abscesso Encefálico/microbiologia , Abscesso Encefálico/patologia , Bactérias/classificação , Bactérias/isolamento & purificação , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/terapia , Pequim/epidemiologia , Abscesso Encefálico/epidemiologia , Abscesso Encefálico/terapia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Resultado do Tratamento
7.
Cell Death Dis ; 11(11): 971, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184264

RESUMO

Vagus nerve stimulation (VNS) restores autonomic balance, suppresses inflammation action and minimizes cardiomyocyte injury. However, little knowledge is known about the VNS' role in cardiomyocyte phenotype, sarcomere organization, and energy metabolism of infarcted hearts. VNS in vivo and acetylcholine (ACh) in vitro optimized the levels of α/ß-MHC and α-Actinin positive sarcomere organization in cardiomyocytes while reducing F-actin assembly of cardiomyocytes. Consistently, ACh improved glucose uptake while decreasing lipid deposition in myocytes, correlating both with the increase of Glut4 and CPT1α and the decrease of PDK4 in infarcted hearts in vivo and myocytes in vitro, attributing to improvement in both glycolysis by VEGF-A and lipid uptake by VEGF-B in response to Ach. This led to increased ATP levels accompanied by the repaired mitochondrial function and the decreased oxygen consumption. Functionally, VNS improved the left ventricular performance. In contrast, ACh-m/nAChR inhibitor or knockdown of VEGF-A/B by shRNA powerfully abrogated these effects mediated by VNS. On mechanism, ACh decreased the levels of nuclear translocation of FoxO3A in myocytes due to phosphorylation of FoxO3A by activating AKT. FoxO3A overexpression or knockdown could reverse the specific effects of ACh on the expression of VEGF-A/B, α/ß-MHC, Glut4, and CPT1α, sarcomere organization, glucose uptake and ATP production. Taken together, VNS optimized cardiomyocytes sarcomere organization and energy metabolism to improve heart function of the infarcted heart during the process of delaying and/or blocking the switch from compensated hypertrophy to decompensated heart failure, which were associated with activation of both P13K/AKT-FoxO3A-VEGF-A/B signaling cascade.


Assuntos
Proteína Forkhead Box O3/metabolismo , Insuficiência Cardíaca/metabolismo , Miócitos Cardíacos/metabolismo , Sarcômeros/metabolismo , Estimulação do Nervo Vago/métodos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator B de Crescimento do Endotélio Vascular/metabolismo , Animais , Diferenciação Celular/fisiologia , Metabolismo Energético , Insuficiência Cardíaca/patologia , Masculino , Miócitos Cardíacos/patologia , Fenótipo , Ratos , Ratos Sprague-Dawley , Sarcômeros/patologia , Transdução de Sinais
8.
J Neurovirol ; 26(2): 273-276, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31654372

RESUMO

This case report presents a 1-year-old boy from China, with sudden onset of fever, convulsion, and sleepiness, screened for viral DNA in blood and cerebrospinal fluid (CSF) sample using next-generation sequencing (NGS) to diagnose herpes simplex virus type 1 (HSV-1) encephalitis, further validated by PCR. After acyclovir treatment, the patient's symptom disappeared and HSV-1 DNA unique reads decreased from 4290 to zero in CSF, and from 23 to zero in blood detected by NGS. The clinical presentation and outcome were consistent with the pathogenic diagnostic results of NGS. NGS of CSF samples can be used as a diagnostic assay for HSV-1 encephalitis and also might be a semi-quantitative method for evaluation of treatment effect.


Assuntos
DNA Viral/líquido cefalorraquidiano , Encefalite por Herpes Simples/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Lactente , Masculino , Análise de Sequência de DNA/métodos , Simplexvirus
9.
Stem Cell Res Ther ; 10(1): 294, 2019 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547879

RESUMO

INTRODUCTION: Accumulation of vascular smooth muscle cells (VSMCs) within the neointimal region is a hallmark of atherosclerosis and vessel injury. Evidence has shown that Sca-1-positive (Sca-1+) progenitor cells residing in the vascular adventitia play a crucial role in VSMC assemblages and intimal lesions. However, the underlying mechanisms, especially in the circumstances of vascular injury, remain unknown. METHODS AND RESULTS: The neointimal formation model in rats was established by carotid artery balloon injury using a 2F-Forgaty catheter. Most Sca-1+ cells first appeared at the adventitia of the vascular wall. S100B expressions were highest within the adventitia on the first day after vessel injury. Along with the sequentially increasing trend of S100B expression in the intima, media, and adventitia, respectively, the numbers of Sca-1+ cells were prominently increased at the media or neointima during the time course of neointimal formation. Furthermore, the Sca-1+ cells were markedly increased in the tunica media on the third day of vessel injury, SDF-1α expressions were obviously increased, and SDF-1α levels and Sca-1+ cells were almost synchronously increased within the neointima on the seventh day of vessel injury. These effects could effectually be reversed by knockdown of S100B by shRNA, RAGE inhibitor (SPF-ZM1), or CXCR4 blocker (AMD3100), indicating that migration of Sca-1+ cells from the adventitia into the neointima was associated with S100B/RAGE and SDF-1α/CXCR4. More importantly, the intermediate state of double-positive Sca-1+ and α-SMA cells was first found in the neointima of injured arteries, which could be substantially abrogated by using shRNA for S100B or blockade of CXCR4. S100B dose-dependently regulated SDF-1α expressions in VSMCs by activating PI3K/AKT and NF-κB, which were markedly abolished by PI3K/AKT inhibitor wortmannin and enhanced by p65 blocker PDTC. Furthermore, S100B was involved in human umbilical cord-derived Sca-1+ progenitor cells' differentiation into VSMCs, especially in maintaining the intermediate state of double-positive Sca-1+ and α-SMA. CONCLUSIONS: S100B triggered neointimal formation in rat injured arteries by maintaining the intermediate state of double-positive Sca-1+ progenitor and VSMCs, which were associated with direct activation of RAGE by S100B and indirect induction of SDF-1α by activating PI3K/AKT and NF-κB.


Assuntos
Ataxina-1/metabolismo , Lesões das Artérias Carótidas/metabolismo , Mioblastos/metabolismo , Miócitos de Músculo Liso/metabolismo , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Túnica Adventícia/citologia , Túnica Adventícia/fisiologia , Animais , Ataxina-1/genética , Lesões das Artérias Carótidas/patologia , Células Cultivadas , Humanos , Músculo Liso Vascular/citologia , Mioblastos/citologia , Miócitos de Músculo Liso/citologia , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Regeneração , Subunidade beta da Proteína Ligante de Cálcio S100/genética , Túnica Íntima/citologia , Túnica Íntima/fisiologia
10.
Medicine (Baltimore) ; 98(28): e16108, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305394

RESUMO

BACKGROUND: The treatment methods about surgery, chemotherapy, and radiation therapy were recommended for gastric cancer (GC) patients by National Comprehensive Cancer Network (NCCN) guidelines. However, for the advanced gastric cancer patients or with metastatic lesions who have lost their chance of surgery, the current adjuvant chemotherapy treatments are still controversial. Therefore, this network meta-analysis is mainly to assess the relative efficacy of different adjuvant chemotherapy regimens for advanced gastric cancer (AGC). METHODS: In order to compare the relative efficacy among different adjuvant chemotherapy regimens for AGC patients, randomized controlled trials (RCTs) and non-RCTs were systematic searched in PubMed, Web of Science, Clinical Trials, Cochrane Library and Embase database. R-3.4.1 software will be used for data analysis. The risk of bias in RCTs and non-RCTs will be evaluated through the risk of bias tool from the Cochrane Handbook version 5.1.0 and non-randomized studies of interventions (ROBINS-I), respectively. RESULTS AND CONCLUSION: The results of this network meta-analysis will evaluate the relative effectiveness and rank the interventions among all chemotherapy methods for unresectable AGC patients, and provide more evidence-based guidance in clinical practice. PROTOCOL REGISTRATION NUMBER: CRD42018111835.


Assuntos
Quimioterapia Adjuvante , Neoplasias Gástricas , Humanos , Metanálise em Rede , Neoplasias Gástricas/terapia , Metanálise como Assunto
11.
Int J Syst Evol Microbiol ; 69(9): 2767-2774, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31237538

RESUMO

In this study, two bacterial strains designated B210T and SEH01T, isolated from coastal sediment sampled in Weihai, PR China, were characterized using a polyphasic approach. Strains were Gram-stain-negative, facultative anaerobic, rod-shaped and motile. According to the results of phylogenetic analyses based on their 16S rRNA genes, these two strains should be classified under the order Bradymonadales and they both show <90 % sequence similarities with Bradymonas sediminis FA350T. Moreover, strain B210T showed 98.6 % sequence similarity to strain SEH01T. Genomic characteristics including average nucleotide identity and in silico DNA-DNA hybridization values clearly separated strain B210T from strain SEH01T. The sole quinone of these two strains was menaquinone MK-7, and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified lipid. Iso-C15 : 0 was the major fatty acid in both strains B210T and SEH01T, and iso-C14 : 0 3-OH was also a major fatty acid for strain SEH01T. Based on the polyphasic analysis, these two strains represent two novel species of a new genus within the family Bradymonadaceae. Consequently, the novel genus Lujinxingia gen. nov. is proposed, containing two new species Lujinxingia litoralis gen. nov. sp. nov. and Lujinxingia sediminis sp. nov., with strain B210T (=KCTC 42951T=CGMCC 1.16770T) and strain SEH01T (=KCTC 42950T=DSM 101859T) as the type strains, respectively.


Assuntos
Deltaproteobacteria/classificação , Sedimentos Geológicos/microbiologia , Filogenia , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Deltaproteobacteria/isolamento & purificação , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
12.
BMC Infect Dis ; 19(1): 495, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164085

RESUMO

BACKGROUND: There is currently no research on the diagnostic value of metagenomic next-generation sequencing (mNGS) for a single pathogens in CSF. The aim of this study was to analyse the value of mNGS for identifying Streptococcus pneumoniae (S. pneumoniae) in paediatric bacterial meningitis. METHODS: Bacterial meningitis (BM) cases from October 23, 2014, to December 31, 2016, and December 1, 2017, to July 31, 2018 at Beijing Children's Hospital were reviewed. Clinical features and pathogens were analysed. RESULTS: We diagnosed 135 patients with BM in this study. A total of 43 S. pneumoniae were identified by combination methods. 26/135 (19.3%) patients had positive results in S. pneumoniae by blood and/or cerebrospinal fluid (CSF) culture. Alere BinaxNow®Streptococcus pneumoniae Antigen test was positive in 35/135(25.9%) cases. 32/135 (23.7%) S. pneumoniae were identified by mNGS. Six CSF samples were identified as S. pneumoniae only by mNGS technology. Taking culture as the gold standard, the sensitivity and specificity of mNGS for diagnosing S. pneumoniae meningitis were 73.1 and 88.1%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of diagnosing S. pneumoniae meningitis by mNGS were 59.4 and 93.2%, respectively. When comparison between mNGS and combined tests (culture and Alere BinaxNow®Streptococcus pneumoniae Antigen test), the sensitivity and specificity of mNGS for S. pneumoniae identification were 70.3 and 93.9%, the PPV and NPV in the identification of S. pneumoniae by mNGS were 81.4 and 89.3%, respectively. The difference in number of unique reads of S. pneumoniaein from CSF sample (< 14 days onset) and CSF sample (> 14 days from onset) was statistically significant (170.5 VS. 13, P = 0.019). The difference in the collected time of CSF for culture and mNGS was statistically significant (4 days VS. 14 days, P < 0.001). CONCLUSIONS: mNGS has high sensitivity and specificity for S. pneumoniae identification. The pathogen load (number of unique reads) of S. pneumonia is related to the CSF collection time. mNGS was less affected than culture by the use of antibiotics before CSF collection.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Meningites Bacterianas/diagnóstico , Metagenômica/métodos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Adolescente , Fatores Etários , Antígenos de Bactérias/análise , Antígenos de Bactérias/sangue , Antígenos de Bactérias/líquido cefalorraquidiano , Antígenos de Bactérias/genética , Criança , Pré-Escolar , Testes Diagnósticos de Rotina , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Meningites Bacterianas/sangue , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/microbiologia , Pediatria/métodos , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , Sensibilidade e Especificidade
13.
J Cell Physiol ; 234(12): 22921-22934, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31148189

RESUMO

Bax triggers cell apoptosis by permeabilizing the outer mitochondrial membrane, leading to membrane potential loss and cytochrome c release. However, it is unclear if proteasomal degradation of Bax is involved in the apoptotic process, especially in heart ischemia-reperfusion (I/R)-induced injury. In the present study, KPC1 expression was heightened in left ventricular cardiomyocytes of patients with coronary heart disease (CHD), in I/R-myocardium in vivo and in hypoxia and reoxygenation (H/R)-induced cardiomyocytes in vitro. Overexpression of KPC1 reduced infarction size and cell apoptosis in I/R rat hearts. Similarly, the forced expression of KPC1 restored mitochondrial membrane potential (MMP) and cytochrome c release driven by H/R in H9c2 cells, whereas reducing cell apoptosis, and knockdown of KPC1 by short-hairpin RNA (shRNA) deteriorated cell apoptosis induced by H/R. Mechanistically, forced expression of KPC1 promoted Bax protein degradation, which was abolished by proteasome inhibitor MG132, suggesting that KPC1 promoted proteasomal degradation of Bax. Furthermore, KPC1 prevented basal and apoptotic stress-induced Bax translocation to mitochondria. Bax can be a novel target for the antiapoptotic effects of KPC1 on I/R-induced cardiomyocyte apoptosis and render mechanistic penetration into at least a subset of the mitochondrial effects of KPC1.


Assuntos
Doença das Coronárias/genética , Mitocôndrias/genética , Complexos Ubiquitina-Proteína Ligase/genética , Proteína X Associada a bcl-2/genética , Animais , Apoptose/genética , Hipóxia Celular/genética , Sobrevivência Celular/genética , Doença das Coronárias/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Humanos , Potencial da Membrana Mitocondrial/genética , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteólise , Ratos , Transdução de Sinais/genética
14.
J Infect ; 78(4): 323-337, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30659857

RESUMO

In this study, we applied metagenomic next-generation sequencing (mNGS) to detect the causative pathogens in brain abscess samples from 4 pediatric patients. NGS could offer unbiased sequencing and rapid diagnosis of causative pathogens, moreover, it could detect multiple pathogenic microorganisms from abscess samples. In our study, Fusobacterium nucleatum, and Streptococcus intermedius or combinations of them were found in 3/4 of polymicrobial brain abscesses. Internal organ abscesses are illustrative of the shortcomings of bacterial culture. NGS has the ability to identify both common and rare pathogens without any prior suspicious needed, and is able to offer a new platform for quantification of all detected microorganisms. Our study displayed the possible potential that NGS is about to provide the diagnostic tools that can characterize even the most complex microbial communities during brain abscesses and is less affected by prior antibiotic exposure.


Assuntos
Abscesso Encefálico , Criança , Sequenciamento de Nucleotídeos em Larga Escala , Humanos
17.
Int J Infect Dis ; 74: 47-53, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30100536

RESUMO

OBJECTIVE: To explore the clinical characteristics and etiology of bacterial meningitis (BM) in Chinese children. METHOD: BM cases in children 28days to 18 years old were collected from January 2014-December 2016 and screened according to World Health Organization standards. Clinical features, pathogens, and resistance patterns were analyzed. RESULTS: Overall, 837 cases were classified into five age groups: 28 days-2 months (17.0%), 3-11 months (27.8%), 12-35 months (24.0%), 3-6 years (13.9%), and >6years (17.3%). Major pathogens were Streptococcus pneumoniae (S. pneumoniae, n=136, 46.9%), group B Streptococcus (GBS, n=29, 10.0%), and Escherichia coli (E. coli, n=23, 7.9%). In infants <3 months old, GBS (46.5%) and E. coli (23.3%) were most common; in children >3 months old, S. pneumoniae (54.7%), which had a penicillin non-susceptibility rate of 55.4% (36/65), was most frequent. The resistance rates of S. pneumoniae and E. coli to cefotaxime and ceftriaxone were 14.0%/40.0% and 11.3%/68.4%, respectively. All GBS isolates were sensitive to penicillin. CONCLUSIONS: The occurrence of BM peaked in the first year of life, while S. pneumoniae was the predominant pathogen in children >3months of old. The antibiotic resistance of S. pneumoniae was a concern.


Assuntos
Escherichia coli/isolamento & purificação , Meningites Bacterianas/microbiologia , Streptococcus agalactiae/isolamento & purificação , Streptococcus pneumoniae/isolamento & purificação , Adolescente , Antibacterianos/farmacologia , Cefotaxima/farmacologia , Ceftriaxona/farmacologia , Criança , Pré-Escolar , China/epidemiologia , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/fisiologia , Feminino , Humanos , Lactente , Masculino , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/epidemiologia , Testes de Sensibilidade Microbiana , Penicilina G/farmacologia , Estudos Retrospectivos , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/genética , Streptococcus agalactiae/fisiologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/fisiologia
18.
Cell Physiol Biochem ; 48(2): 433-449, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30016789

RESUMO

BACKGROUND/AIMS: Vagus nerve stimulation (VNS) suppresses arrhythmic activity and minimizes cardiomyocyte injury. However, how VNS affects angiogenesis/arteriogenesis in infarcted hearts, is poorly understood. METHODS: Myocardial infarction (MI) was achieved by ligation of the left anterior descending coronary artery (LAD) in rats. 7 days after LAD, stainless-steel wires were looped around the left and right vagal nerve in the neck for vagus nerve stimulation (VNS). The vagal nerve was stimulated with regular pulses of 0.2ms duration at 20 Hz for 10 seconds every minute for 4 hours, and then ACh levels by ELISA in cardiac tissue and serum were evaluated for its release after VNS. Three and 14 days after VNS, Real-time PCR, immunostaining and western blot were respectively used to determine VEGF-A/B expressions and α-SMA- and CD31-postive vessels in VNS-hearts with pretreatment of α7-nAChR blocker mecamylamine (10 mg/kg, ip) or mACh-R blocker atropine (10 mg/kg, ip) for 1 hour. The coronary function and left ventricular performance were analyzed by Langendorff system and hemodynamic parameters in VNS-hearts with pretreatment of VEGF-A/B-knockdown or VEGFR blocker AMG706. Coronary arterial endothelial cells proliferation, migration and tube formation were evaluated for angiogenesis following the stimulation of VNS in coronary arterial smooth muscle cells (VSMCs). RESULTS: VNS has been shown to stimulate VEGF-A and VEGF-B expressions in coronary arterial smooth muscle cells (VSMCs) and endothelial cells (ECs) with an increase of α-SMA- and CD31-postive vessel number in infarcted hearts. The VNS-induced VEGF-A/B expressions and angiogenesis were abolished by m-AChR inhibitor atropine and α7-nAChR blocker mecamylamine in vivo. Interestingly, knockdown of VEGF-A by shRNA mainly reduced VNS-mediated formation of CD31+ microvessels. In contrast, knockdown of VEGF-B powerfully abrogated VNS-induced formation of α-SMA+ vessels. Consistently, VNS-induced VEGF-A showed a greater effect on EC tube formation as compared to VNS-induced VEGF-B. Moreover, VEGF-A promoted EC proliferation and VSMC migration while VEGF-B induced VSMC proliferation and EC migration in vitro. Mechanistically, vagal neurotransmitter acetylcholine stimulated VEGF-A/B expressions through m/nACh-R/PI3K/Akt/Sp1 pathway in EC. Functionally, VNS improved the coronary function and left ventricular performance. However, blockade of VEGF receptor by antagonist AMG706 or knockdown of VEGF-A or VEGF-B by shRNA significantly diminished the beneficial effects of VNS on ventricular performance. CONCLUSION: VNS promoted angiogenesis/arteriogenesis to repair the infracted heart through the synergistic effects of VEGF-A and VEGF-B.


Assuntos
Infarto do Miocárdio/terapia , Estimulação do Nervo Vago , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator B de Crescimento do Endotélio Vascular/metabolismo , Acetilcolina/análise , Acetilcolina/sangue , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Indóis/farmacologia , Masculino , Microvasos/citologia , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Niacinamida/administração & dosagem , Niacinamida/farmacologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Muscarínicos/química , Receptores Muscarínicos/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genética , Fator B de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator B de Crescimento do Endotélio Vascular/genética , Receptor Nicotínico de Acetilcolina alfa7/antagonistas & inibidores , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
19.
BMC Infect Dis ; 18(1): 248, 2018 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-29855274

RESUMO

BACKGROUND: Bloodstream infections (BSI) caused by carbapenem-resistant K. pneumoniae (CRKP) are associated with high rates of morbidity and mortality. Early identification of patients at highest risk is very important. The aim of this study was to describe the clinical characteristics and mortality of K. pneumoniae BSI and to identify risk factors associated with CRKP BSI among paediatric patients. METHODS: From January 2011 to December 2014, a retrospective case-control study was conducted at Beijing Children's Hospital, China. Risk factors for CRKP BSI and for K. pneumoniae BSI-related death were evaluated. Patients with BSI caused by K. pneumoniae were identified from the microbiology laboratory database. Data regarding demographic, microbiological and clinical characteristics, therapy and outcome were collected from the medical records. RESULTS: A total of 138 patients with K. pneumoniae BSI were enrolled, including 54 patients with CRKP BSI and 84 patients with carbapenem-susceptible K. pneumoniae (CSKP) BSI. Most of the BSI (114; 82.6%) were healthcare-associated, while the rest (24; 17.4%) were community-acquired. Hematologic malignancies (odds ratio (OR):4.712, [95% CI: 2.181-10.180], P <  0.001) and previous cephalosporin administration (OR: 3.427, [95% CI: 1.513-7.766], P = 0.003) were found to be associated with the development of CRKP BSI. 28-day mortality of K. pneumoniae BSI was 8.7%. Mechanical ventilation (OR:9.502, [95% CI: 2.098-43.033], P = 0.003), septic shock (OR:6.418, [95% CI: 1.342-30.686], P = 0.020), and isolation of CRKP (OR:9.171, [95% CI: 1.546-54.416], P = 0.015) were independent risk factors for 28-day mortality of K. pneumoniae BSI. CONCLUSION: Hematologic malignancies and previous cephalosporin administration were associated with the development of CRKP BSI, while mechanical ventilation, septic shock and CRKP infection were independent mortality predictors for K. pneumoniae BSI. More attention should be paid to CRKP BSI in the paediatric population.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/epidemiologia , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/isolamento & purificação , Adolescente , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Estudos de Casos e Controles , Criança , Mortalidade da Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/mortalidade , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
20.
Data Brief ; 16: 266-270, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29204471

RESUMO

In the previous report, Meox1 was found to promote SMCs phenotypic modulation and injury-induced vascular remodeling by regulating the FAK-ERK1/2-autophagy signaling cascade (Wu et al., 2017) [1]. Here, we presented new original data on the involvement of Mesoderm/mesenchyme homeobox gene l (Meox1) in balloon-injury-induced neointima formation of rat. In rat carotid artery balloon injury model to induce vascular remodeling, Meox1 was induced in vascular smooth muscle cell (SMCs) of rat carotid arteries. Most proliferating cell nuclear antigen (PCNA)-positive cells also expressed Meox1. These data suggested that Meox1 may be involved in SMCs proliferation during injury-induced neointima formation. Furthermore, knocked down its expression in injured arteries by adenoviral delivery of Meox1 short hairpin RNA (shRNA) (shMeox1), neointima formation was significantly inhibited. Elastin staining also confirmed the reduction of neointima in Meox1 shRNA-transduced arteries. Moreover, knockdown of Meox1 decreased the collagen production/deposition that was significantly increased in neointima induced by balloon injury.

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