RESUMO
Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and progression of tumors, leading to resistance and poor prognosis. Activation of STAT3 signaling is frequently detected in hepatocellular carcinoma (HCC), but potent and less toxic STAT3 inhibitors have not been discovered. Here, based on antisense technology, we designed a series of stabilized modified antisense oligonucleotides targeting STAT3 mRNA (STAT3 ASOs). Treatment with STAT3 ASOs decreased the STAT3 mRNA and protein levels in HCC cells. STAT3 ASOs significantly inhibited the proliferation, survival, migration, and invasion of cancer cells by specifically perturbing STAT3 signaling. Treatment with STAT3 ASOs decreased the tumor burden in an HCC xenograft model. Moreover, aberrant STAT3 signaling activation is one of multiple signaling pathways involved in sorafenib resistance in HCC. STAT3 ASOs effectively sensitized resistant HCC cell lines to sorafenib in vitro and improved the inhibitory potency of sorafenib in a resistant HCC xenograft model. The developed STAT3 ASOs enrich the tools capable of targeting STAT3 and modulating STAT3 activity, serve as a promising strategy for treating HCC and other STAT3-addicted tumors, and alleviate the acquired resistance to sorafenib in HCC patients. A series of novel STAT3 antisense oligonucleotide were designed and showed potent anti-cancer efficacy in hepatocellular carcinoma in vitro and in vivo by targeting STAT3 signaling. Moreover, the selected STAT3 ASOs enhance sorafenib sensitivity in resistant cell model and xenograft model.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas , Fator de Transcrição STAT3 , Sorafenibe , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Animais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos Nus , Oligonucleotídeos Antissenso/farmacologia , Oligonucleotídeos Antissenso/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de Xenoenxerto , Movimento Celular/efeitos dos fármacos , Masculino , Transdução de Sinais/efeitos dos fármacos , Oligonucleotídeos/farmacologiaRESUMO
In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.
Assuntos
Agnosia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Estimulação Magnética Transcraniana , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Encéfalo , Córtex CerebralRESUMO
Resistance to epidermal growth factor receptor (EGFR) inhibitors, from the first-generation erlotinib to the third generation osimertinib, is a clinical challenge in the treatment of patients with EGFR-mutant lung adenocarcinoma. Our previous work found that a novel allosteric inhibitor of phosphoglycerate mutase 1 (PGAM1), HKB99, restrains erlotinib resistance in lung adenocarcinoma cells. However, the role of HKB99 in osimertinib resistance and its underlying molecular mechanism remains to be elucidated. Herein, we found that IL-6/JAK2/STAT3 signaling pathway is aberrantly activated in both erlotinib and osimertinib resistant cells. Importantly, HKB99 significantly blocks the interaction of PGAM1 with JAK2 and STAT3 via the allosteric sites of PGAM1, which leads to inactivation of JAK2/STAT3 and thereby disrupts IL-6/JAK2/STAT3 signaling pathway. Consequently, HKB99 remarkably restores EGFR inhibitor sensitivity and exerts synergistic tumoricidal effect. Additionally, HKB99 alone or in combination with osimertinib down-regulated the level of p-STAT3 in xenograft tumor models. Collectively, this study identifies PGAM1 as a key regulator in IL-6/JAK2/STAT3 axis in the development of resistance to EGFR inhibitors, which could serve as a therapeutic target in lung adenocarcinoma with acquired resistance to EGFR inhibitors.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Cloridrato de Erlotinib/farmacologia , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Interleucina-6/genética , Interleucina-6/farmacologia , Interleucina-6/uso terapêutico , Fosfoglicerato Mutase/metabolismo , Fosfoglicerato Mutase/farmacologia , Resistencia a Medicamentos Antineoplásicos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Receptores ErbB , Transdução de Sinais , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Mutação , Linhagem Celular Tumoral , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Janus Quinase 2/farmacologiaRESUMO
The UK screening and treatment of retinopathy of prematurity (ROP) updated 2022 guidelines were developed by a multidisciplinary guideline development group from the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists, following the standards of the National Institute for Health and Care Excellence. They were published on the websites of the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists in March 2022, and formally published in Early Human Development in March 2023. The guidelines provide evidence-based recommendations for the screening and treatment of ROP. The most significant change in the 2022 updated version compared to the previous guidelines is the lowering of the gestational age screening criterion to below 31 weeks. The treatment section covers treatment indications, timing, methods, and follow-up visits of ROP. This article interprets the guidelines and compares them with ROP guidelines/consensus in China, providing a reference for domestic peers.
Assuntos
Guias de Prática Clínica como Assunto , Retinopatia da Prematuridade , Humanos , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/terapia , Recém-Nascido , Reino Unido , Triagem Neonatal , Idade GestacionalRESUMO
Although long noncoding RNAs (lncRNAs) have significant tissue specificity, their expression and variability in single cells remain unclear. Here, we developed ColorCells (http://rna.sysu.edu.cn/colorcells/), a resource for comparative analysis of lncRNAs expression, classification and functions in single-cell RNA-Seq data. ColorCells was applied to 167 913 publicly available scRNA-Seq datasets from six species, and identified a batch of cell-specific lncRNAs. These lncRNAs show surprising levels of expression variability between different cell clusters, and has the comparable cell classification ability as known marker genes. Cell-specific lncRNAs have been identified and further validated by in vitro experiments. We found that lncRNAs are typically co-expressed with the mRNAs in the same cell cluster, which can be used to uncover lncRNAs' functions. Our study emphasizes the need to uncover lncRNAs in all cell types and shows the power of lncRNAs as novel marker genes at single cell resolution.
Assuntos
Bases de Dados de Ácidos Nucleicos , Regulação da Expressão Gênica , RNA Longo não Codificante , Análise de Célula Única , Software , Animais , Humanos , Anotação de Sequência Molecular , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genéticaRESUMO
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have achieved satisfactory clinical effects in the therapy of non-small cell lung cancer (NSCLC), but acquired resistance limits their clinical application. NRF2 has been shown to enhance the resistance to apoptosis induced by radiotherapy and some chemotherapy. In this study, we investigated the role of NRF2 in resistance to EGFR-TKIs. We showed that NRF2 protein levels were markedly increased in a panel of EGFR-TKI-resistant NSCLC cell lines due to slow degradation of NRF2 protein. NRF2 knockdown overcame the resistance to EGFR-TKIs in HCC827ER and HCC827GR cells. Furthermore, we demonstrated that NRF2 imparted EGFR-TKIs resistance in HCC827 cells via upregulation of GPX4 and SOD2, and suppression of GPX4 and SOD2 reversed resistance to EGFR-TKIs. Thus, we conclude that targeting NRF2-GPX4/SOD2 pathway is a potential strategy for overcoming resistance to EGFR-TKIs.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Neoplasias Pulmonares/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Superóxido Dismutase/metabolismo , Carbolinas/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/fisiologia , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/farmacologia , Gefitinibe/farmacologia , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Fator 2 Relacionado a NF-E2/genética , Inibidores de Proteínas Quinases/farmacologia , RNA Interferente Pequeno/farmacologia , Superóxido Dismutase/genética , Regulação para Cima/fisiologiaRESUMO
More than 100 distinct chemical modifications to RNA have been characterized so far. However, the prevalence, mechanisms and functions of various RNA modifications remain largely unknown. To provide transcriptome-wide landscapes of RNA modifications, we developed the RMBase v2.0 (http://rna.sysu.edu.cn/rmbase/), which is a comprehensive database that integrates epitranscriptome sequencing data for the exploration of post-transcriptional modifications of RNAs and their relationships with miRNA binding events, disease-related single-nucleotide polymorphisms (SNPs) and RNA-binding proteins (RBPs). RMBase v2.0 was expanded with â¼600 datasets and â¼1 397 000 modification sites from 47 studies among 13 species, which represents an approximately 10-fold expansion when compared with the previous release. It contains â¼1 373 000 N6-methyladenosines (m6A), â¼5400 N1-methyladenosines (m1A), â¼9600 pseudouridine (Ψ) modifications, â¼1000 5-methylcytosine (m5C) modifications, â¼5100 2'-O-methylations (2'-O-Me), and â¼2800 modifications of other modification types. Moreover, we built a new module called 'Motif' that provides the visualized logos and position weight matrices (PWMs) of the modification motifs. We also constructed a novel module termed 'modRBP' to study the relationships between RNA modifications and RBPs. Additionally, we developed a novel web-based tool named 'modMetagene' to plot the metagenes of RNA modification along a transcript model. This database will help researchers investigate the potential functions and mechanisms of RNA modifications.
Assuntos
Bases de Dados Genéticas , Perfilação da Expressão Gênica , Processamento Pós-Transcricional do RNA , Análise de Sequência de RNA , 5-Metilcitosina/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Sítios de Ligação , Doença/genética , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Pseudouridina/metabolismo , RNA Longo não Codificante/química , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismo , Ratos , Interface Usuário-ComputadorRESUMO
Although thousands of pseudogenes have been annotated in the human genome, their transcriptional regulation, expression profiles and functional mechanisms are largely unknown. In this study, we developed dreamBase (http://rna.sysu.edu.cn/dreamBase) to facilitate the investigation of DNA modification, RNA regulation and protein binding of potential expressed pseudogenes from multidimensional high-throughput sequencing data. Based on â¼5500 ChIP-seq and DNase-seq datasets, we identified genome-wide binding profiles of various transcription-associated factors around pseudogene loci. By integrating â¼18 000 RNA-seq data, we analysed the expression profiles of pseudogenes and explored their co-expression patterns with their parent genes in 32 cancers and 31 normal tissues. By combining microRNA binding sites, we demonstrated complex post-transcriptional regulation networks involving 275 microRNAs and 1201 pseudogenes. We generated ceRNA networks to illustrate the crosstalk between pseudogenes and their parent genes through competitive binding of microRNAs. In addition, we studied transcriptome-wide interactions between RNA binding proteins (RBPs) and pseudogenes based on 458 CLIP-seq datasets. In conjunction with epitranscriptome sequencing data, we also mapped 1039 RNA modification sites onto 635 pseudogenes. This database will provide insights into the transcriptional regulation, expression, functions and mechanisms of pseudogenes as well as their roles in biological processes and diseases.
Assuntos
Bases de Dados Genéticas , Pseudogenes , DNA/genética , DNA/metabolismo , Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Ligação Proteica/genética , RNA/genética , RNA/metabolismo , Processamento Pós-Transcricional do RNA , Proteínas de Ligação a RNA/metabolismo , Análise de Sequência de RNARESUMO
Introduction: Increase in right relative to left frontal electroencephalography (EEG) activity has been observed in patients with schizophrenia, both in cognitive tasks and during rest; and this lateralisation may be related to the severity of schizotypal traits. Methods: We used the Schizotypal Personality Questionnaire (SPQ) to assess schizotypal traits, and examined the correlation between these traits and resting EEG frontal asymmetry (left-right) in 52 college students, as well as the reliability of this correlation over a three-month interval. Results: A higher total score on the SPQ was correlated with reduced asymmetry in different frequency bands: gamma and beta2 frequency bands at baseline, and delta and alpha frequency bands three months later. Additionally, the reduced left relative to right frontal gamma and beta2 asymmetry was correlated with the participants' verbal fluency ability. However, this correlation was no longer statistically significant after the total SPQ score was controlled. Conclusions: These findings suggest that resting frontal EEG asymmetry is correlated with powers in different frequency bands, and may be an endophenotype for schizophrenia spectrum disorders.
Assuntos
Esquizofrenia , Transtorno da Personalidade Esquizotípica , Eletroencefalografia/métodos , Humanos , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
The abnormal transcriptional regulation of non-coding RNAs (ncRNAs) and protein-coding genes (PCGs) is contributed to various biological processes and linked with human diseases, but the underlying mechanisms remain elusive. In this study, we developed ChIPBase v2.0 (http://rna.sysu.edu.cn/chipbase/) to explore the transcriptional regulatory networks of ncRNAs and PCGs. ChIPBase v2.0 has been expanded with â¼10 200 curated ChIP-seq datasets, which represent about 20 times expansion when comparing to the previous released version. We identified thousands of binding motif matrices and their binding sites from ChIP-seq data of DNA-binding proteins and predicted millions of transcriptional regulatory relationships between transcription factors (TFs) and genes. We constructed 'Regulator' module to predict hundreds of TFs and histone modifications that were involved in or affected transcription of ncRNAs and PCGs. Moreover, we built a web-based tool, Co-Expression, to explore the co-expression patterns between DNA-binding proteins and various types of genes by integrating the gene expression profiles of â¼10 000 tumor samples and â¼9100 normal tissues and cell lines. ChIPBase also provides a ChIP-Function tool and a genome browser to predict functions of diverse genes and visualize various ChIP-seq data. This study will greatly expand our understanding of the transcriptional regulations of ncRNAs and PCGs.
Assuntos
Imunoprecipitação da Cromatina , Bases de Dados Genéticas , Redes Reguladoras de Genes , Proteínas/genética , RNA não Traduzido/genética , Análise de Sequência de DNA , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação , Proteínas de Ligação a DNA/metabolismo , Perfilação da Expressão Gênica , Genômica , Humanos , Metadados , Anotação de Sequência Molecular , RNA não Traduzido/metabolismo , Elementos Reguladores de Transcrição , Análise de Sequência de RNA , Software , Transcrição GênicaRESUMO
OBJECTIVE: To compare the effect and safety of prednisolone and adrenocorticotropic hormone (ACTH) in the treatment of infantile spasms (IS). METHODS: Cochrane Library, Embase, PubMed, China Biology Medicine Disc, CNKI, and Wanfang Data were searched for clinical studies on the comparison between prednisolone and ACTH in the treatment of IS. Literature screening, data extraction, and quality assessment were performed. Review Manager 5.3 was used for Meta analysis. RESULTS: Five clinical studies were included according to the inclusion criteria and exclusion criteria. Meta analysis showed that there was no significant difference in the spasm remission rate, spasm remission time, complicating infection rate, and irritability rate between the prednisolone and ACTH treatment groups (P>0.05), but the disappearance rate of hypsarrhythmia in the electroencephalogram was higher in the ACTH treatment group than in the prednisolone treatment group (P<0.05). CONCLUSIONS: The available evidence shows no difference in the clinical efficacy of prednisolone versus ACTH in the treatment of IS. However, ACTH is superior to prednisolone in stabilizing EEG. The two therapies have no difference in the incidence of adverse reactions such as infection and irritability.
Assuntos
Espasmos Infantis , Hormônio Adrenocorticotrópico , Anticonvulsivantes , China , Humanos , Lactente , Prednisolona , Espasmo , Resultado do TratamentoRESUMO
Skeletal muscle is an essential tissue to maintain the normal functions of an organism. It is also closely associated with important economic performance, such as carcass weight, of domestic animals. In recent years, studies using high-throughput sequencing techniques have identified numerous long non-coding RNAs (lncRNAs) with myogenic functions involved in regulation of gene expression at multiple levels, including epigenetic, transcriptional and post-transcriptional regulation. These lncRNAs target myogenic factors, which participate in all processes of skeletal muscle development, including proliferation, migration and differentiation of skeletal muscle stem cells, proliferation, differentiation and fusion of myocytes, muscle hypertrophy and conversion of muscle fiber types. In this review, we summarize the functional roles of lncRNAs in regulation of myogenesis in humans and mice, describe the methods for the analysis of lncRNA function, discuss the progress of lncRNA research in domestic animals, and highlight the current problems and challenges in lncRNA research on livestock production. We hope to provide a useful reference for research on lncRNA in domestic animals, thereby further identifying the molecular regulatory mechanisms in skeletal muscle growth and development.
Assuntos
Animais Domésticos/genética , Músculo Esquelético/crescimento & desenvolvimento , RNA Longo não Codificante/genética , Animais , Animais Domésticos/crescimento & desenvolvimento , Animais Domésticos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Músculo Esquelético/metabolismo , RNA Longo não Codificante/metabolismoRESUMO
Endogenous small non-coding RNAs (sRNAs), including microRNAs, PIWI-interacting RNAs and small interfering RNAs, play important gene regulatory roles in animals and plants by pairing to the protein-coding and non-coding transcripts. However, computationally assigning these various sRNAs to their regulatory target genes remains technically challenging. Recently, a high-throughput degradome sequencing method was applied to identify biologically relevant sRNA cleavage sites. In this study, an integrated web-based tool, StarScan (sRNA target Scan), was developed for scanning sRNA targets using degradome sequencing data from 20 species. Given a sRNA sequence from plants or animals, our web server performs an ultrafast and exhaustive search for potential sRNA-target interactions in annotated and unannotated genomic regions. The interactions between small RNAs and target transcripts were further evaluated using a novel tool, alignScore. A novel tool, degradomeBinomTest, was developed to quantify the abundance of degradome fragments located at the 9-11th nucleotide from the sRNA 5' end. This is the first web server for discovering potential sRNA-mediated RNA cleavage events in plants and animals, which affords mechanistic insights into the regulatory roles of sRNAs. The StarScan web server is available at http://mirlab.sysu.edu.cn/starscan/.
Assuntos
Software , Animais , Humanos , Internet , Clivagem do RNA , RNA de Plantas/química , RNA de Plantas/metabolismo , Pequeno RNA não Traduzido/química , Pequeno RNA não Traduzido/metabolismo , Análise de Sequência de RNARESUMO
27-hydroxycholesterol (27-HC), the most abundant metabolite of cholesterol, is a risk factor for breast cancer. It can increase the proliferation of breast cancer cells and promote the metastasis of breast tumours in mouse models. Myc is a critical oncoprotein overexpressed in breast cancer. However, whether 27-HC affects Myc expression has not been reported. In the current study, we aimed to investigate the effects of 27-HC on Myc and the underlying mechanisms in MCF-7 breast cancer cells. Our data demonstrated that 27-HC activated Myc via increasing its protein stability. Three key negative modulators of Myc protein stability, PP2A, SCP1 and FBW7, were suppressed by 27-HC at the transcriptional level. We performed a data-mining analysis of the chromatin immunoprecipitation with next-generation DNA sequencing (ChIP-Seq) data in the ChIPBase, and discovered that a number of putative transcription factors (TFs), including Myc itself, were involved in the transcriptional regulation of PP2A, SCP1 and FBW7. Our results provide a novel mechanistic insight into the activation of Myc by 27-HC via transcriptional repression of PP2A, SCP1 and FBW7 to increase Myc protein stability in breast cancer cells.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas F-Box/metabolismo , Hidroxicolesteróis/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteína 7 com Repetições F-Box-WD , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Ativação TranscricionalRESUMO
BACKGROUND: Klebsiella pneumoniae has been the dominant pathogen for liver abscesses in several Asian countries. Although the prevalence of K. pneumoniae liver abscess (KLA) in mainland China is increasing recently, the clinical and microbiological characteristics of KLA in China have not been elucidated. METHODS: Clinical and microbiology characteristics of 45 consecutive patients with KLA from a tertiary teaching hospital in China between June 2008 and June 2012 were retrospectively evaluated. RESULTS: Vast majority of the strains were susceptible to main antimicrobial agents. Most of K. pneumoniae strains from pyogenic liver abscess patients belonged to K1/K2 serotype (68.9% for K1 serotype and 20% for K2 serotype). All K. pneumoniae strains were rmpA positive, and 68.9% of these strains were magA positive. Overall, 57.8% (26/45) of K. pneumoniae strains belonged to ST23. Twenty-five of 26 ST23 K. pneumoniae isolates (96.2%) from KLA patients were magA-positive and K1 serotype. Only 28.9% (13/45) of KLA isolates exhibited hypermucoviscous phenotype, which is clinically used as the characteristic of hypervirulent K. pneumoniae (hvKP). Liver abscess sizes in patients infected with hvKP were tend to be larger than those in patients infected with cKP. There was no significant association between the microbiological and clinical characteristics including serotypes, magA and rmpA genotypes, and STs with the metastatic infection and prognosis of KLA. CONCLUSIONS: Neither the serotypes, magA and rmpA genotypes, nor the STs of K. pneumoniae were associated with the metastatic infection and prognosis of KLA. However, further studies with larger sample are needed in the future.
Assuntos
Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Abscesso Hepático Piogênico/microbiologia , Adolescente , Adulto , China/epidemiologia , DNA Bacteriano/genética , Feminino , Genótipo , Humanos , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/isolamento & purificação , Abscesso Hepático Piogênico/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Sorogrupo , Adulto JovemRESUMO
BACKGROUND/PURPOSE: Since little has been reported in previous studies, we aimed to find the clinical and electrophysiologic characteristics associated with childhood Guillain-Barré Syndrome (GBS) in Northeast China. METHODS: The clinical and electrophysiologic data were collected and reviewed retrospectively in 33 children and 105 adults with GBS during the period between 2006 and 2010 from the First Hospital of Jilin University. RESULTS: Most of the children with GBS were older than 8 years of age and symptoms were severe at GBS onset. Simultaneous involvement of four limbs was the most common clinical feature, and cranial nerve involvement was common; however, previous infection, sensory nerve involvement and elevated proteins in cerebrospinal fluid occurred much less in the children with GBS than those in adult patients. Recruited children were classified as having acute inflammatory demyelinating polyneuropathy (AIDP; 41%), acute motor axonal neuropathy (AMAN; 38%), and were unclassified (21%). Electrophysiologic features and prognosis in these children were not different from those in adults. For children with AMAN, the efficacy of intravenous immunoglobulin (IVIg) was not different from that in adults; however, IVIg was not significantly effective for AIDP in these children. CONCLUSION: Childhood GBS in Northeast China exhibits characteristics of clinical and electrophysiologic alternations; early diagnosis and appropriate treatments should be provided accordingly.
Assuntos
Eletrodiagnóstico/métodos , Síndrome de Guillain-Barré/diagnóstico , Adolescente , Adulto , Criança , China/epidemiologia , Feminino , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Incidência , Masculino , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Hematoma expansion (HE) is common in patients with intracerebral hemorrhage (ICH) and associated with a worse outcome. Imaging makers and shorter time from symptom onset are both associated with HE, but prognostic scores based on these parameters individually have not been satisfactory. We hypothesized that a score including both imaging markers of expansion, and time of onset, would improve prediction. METHODS: Patients with supratentorial ICH within 6 h after onset were consecutively recruited from six centers between January 2018 and August 2022. Three markers were used: hypodensities, the blend sign, and the island sign. We first defined frequency of imaging markers (FIM) as the relationship between the number of imaging markers and onset-to-CT time (OCT). The time-adjusted FIM was defined as the ratio of the number of imaging markers to the onset-to-initial imaging time. Multivariate analysis was performed to determine the relationship between FIM and HE. Receiver operating curve analysis was used to identify potential threshold values of FIM that optimally predict HE. In addition, the sensitivity, specificity, positive and negative predictive values (PPVs and NPVs), and the area under the curve (AUC) of the optimal cut-off in predicting HE were calculated. RESULTS: In total, 1488 patients were eligible for inclusion, of whom 418 had incident HE. Multivariate analysis showed that age, male sex, baseline Glasgow Coma Scale score, presence of intraventricular hemorrhage, and FIM were independent predictors of HE (odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.97-0.99; OR = 1.73, 95% CI = 1.28-2.35; OR = 0.87, 95% CI = 0.83-0.92; OR = 0.42, 95% CI = 0.28-0.62; OR = 7.82, 95% CI = 5.86-10.42, respectively). The optimal cut-off point for FIM in predicting HE was 0.63, with sensitivity, specificity, PPV, NPV, and AUC values of 0.69, 0.89, 0.71, 0.88, and 0.83, respectively. CONCLUSION: The FIM adjusted for time since symptom onset is a significant predictor of HE. Its use may allow improved prediction of those patients with ICH who develop HE, and the score may be clinically applicable in the management of patients with ICH.
Assuntos
Acidente Vascular Cerebral , Humanos , Masculino , Acidente Vascular Cerebral/complicações , Hemorragia Cerebral/complicações , Hematoma/diagnóstico por imagem , Hematoma/complicações , Tomografia Computadorizada por Raios X , Angiografia por Tomografia Computadorizada , Estudos RetrospectivosRESUMO
Objective: Maintenance hemodialysis (MHD) patients suffer from enormous physical, mental stress and poor quality of life, so an increasing number of patients are in a long-term state of depression. A prominent feature of MHD patients is chronic persistent inflammation, which is also an important mechanism for the onset of depression. Therefore, finding economically convenient inflammatory markers to predict and diagnose the onset of depression in MHD patients is of great value. As a novel inflammatory marker, systemic immune inflammation index (SII) can more comprehensively reflect the inflammation and immunity level of patients. This study aims to explore the relationship between SII and depressive symptoms in MHD patients. Methods: A cross-sectional study was conducted on 206 MHD patients from three dialysis centers. Based on the Hospital Anxiety and Depression Scale (HADS) scores, patients were divided into non-depression and depression groups. Inter group comparison and multivariate logistic regression analysis were performed to determine whether SII is an independent risk factor for depression in MHD patients. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SII on depression symptoms in MHD patients. Results: According to the HADS scale score, 38.83% of the included patients were in a state of depression. After adjusting for all confounding factors, MHD patients with SII>963.93 had a 4.709 times higher risk of depression than those with SII ≤ 478.32 (OR=4.709, 95% CI 1.821-12.178, P<0.01). ROC analysis showed that SII>685.11 was the best cutoff value for MHD depression patients, and the area under the curve (AUC) was 0.681. Conclusions: High SII is an independent risk factor for depressed MHD patients and an ideal inflammatory marker for predicting and identifying depression in MHD patients as assessed by the HADS scale.
RESUMO
This study aimed to develop a suitable dosage form of volatile oil from wampee leaves and to explore its antibacterial mechanism in vitro. The chemical composition of the volatile oil from wampee leaves was determined by gas chromatography-mass spectrometry (GC-MS). Different microemulsion ratios were tested and their stabilities were investigated to determine the optimal ratio. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the wampee leaves volatile oil emulsion (WVOE) against Salmonella typhimurium (S. typhimurium) and Staphylococcus aureus (S. aureus) were determined using double-dilution and plate-counting methods, respectively. Morphological changes in these two bacteria were observed using scanning electron microscopy. Death, ultrastructural morphology, and biofilm formation were also assessed for S. aureus. Finally, we established an S. aureus-infected Lewis lung carcinoma (LLC) cell model to evaluate the protective effects of the volatile oil emulsion and the associated mechanisms. The volatile oil extracted from wampee leaves contained 37 compounds, of which 96.49% were aromatic hydrocarbons, terpenoids, and their oxygen-containing derivatives. The emulsion was most stable at 1:1 in the oil phase and 1:9 in the water phase. WVOE had poor antibacterial activity against S. typhimurium, but the MIC and MBC against S. aureus were 312.5 and 2,500 µg/mL, respectively. S. aureus survival rates were 84.6%, 14.5%, and 12.8% in the 1/2, 1, and 4 × MIC groups, respectively, compared with 97.2% in the control group. S. typhimurium survival was not affected by WVOE treatment. WVOE administration induced cavity formation and abnormal binary fission, and significantly inhibited biofilm formation in S. aureus cells. The WVOE notably reduced the number of S. aureus and inhibited TLR4, NLRP3, NF-κB, IL-6, IL-18, and TNF-α gene expression in S. aureus-infected LLC cells. The WVOE had a significant inhibitory effect on S. aureus and altered its cell membrane permeability. Moreover, it alleviated inflammation by inhibiting the NF-κB-NLRP3 pathway in S. aureus-infected LLC cells.