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GZF1 was recently reported as a genetic factor associated with Larsen syndrome. Two patients presenting hip dislocation, scoliosis and severe myopia, as well as hearing loss and other abnormal features, were found to carry two novel compounds heterozygous variants in GZF1 (c.397400del, p. Leu133fs; and c.1474del, p. Met492fs) through whole-exome sequencing. The mRNA expression level of L133fs-GZF1 did not significantly differ from that of WT-GZF1. However, no HA-conjugated mutant protein was detected by western blotting, which was also confirmed by immunofluorescence staining. In addition, both mRNA transcription and protein expression levels of M492fs-GZF1 were significantly lower than those of wild type, and HA-tagged M492fs-GZF1 was mainly distributed in the cytoplasm of HEK 293 T cells. These results suggested that the two variants could lead to loss of function of GZF1. Our study was the second to report the association between GZF1 variants and Larsen syndrome. We also provided functional evidence for the pathogenicity of GZF1 variants, which expands the mutation spectrum and offers a basis for functional research on the role of GZF1 in the development of Larsen syndrome.
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Fatores de Transcrição Kruppel-Like/genética , Osteocondrodisplasias/genética , Povo Asiático/genética , Feminino , Variação Genética , Humanos , Osteocondrodisplasias/patologia , Linhagem , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real , Sequenciamento do Exoma , Adulto JovemRESUMO
OBJECTIVE: To evaluate the application value of time to positivity (TTP) for blood culture combined with inflammatory parameters that included immature granulocyte percentage (IG%), immature granulocyte count (IG#), C-reactive protein (CRP), white blood cells (WBC) neutrophil percentage (NE%), and neutrophil-to-lymphocyte ratio (NLR), and to identify bloodstream infections from contamination with coagulase-negative staphylococci (CoNS) in pediatric patients. METHODS: Data of 12 897 inpatients with blood culture CoNS were retrospectively collected and analyzed from January-December 2019 at our hospital. According to pre-defined criteria, they were divided into a CoNS infection group (132 cases) and a CoNS contamination group (124 cases). Infection with Staphylococcus aureus (SA, 27 cases) at the same period was considered a positive control group. ROC curve analysis assisted in determining the value of applying TTP combined with the above-mentioned inflammatory parameters to distinguish CoNS infection from contamination. RESULTS: Among the 256 strains of CoNS, Staphylococcus hominis (55.1%), Staphylococcus epidermidis (32.0%), and Staphylococcus capitis (7.0%) were common. There was no significant difference in the subspecies distribution between the infection and contamination groups. The TTP of the CoNS infection group was significantly lower than the contamination group (P < .05). IG%, IG#, CRP, NE%, and NLR were all higher in the infected group as compared to the contaminated group (P < .05), while WBC was similar among groups. There was also no statistical difference in those parameters when comparing the CoNS infection and SA groups. ROC analysis showed that TTP value in identifying CoNS infection from contamination was the highest with area under the curve (AUC) of 0.913, and the sensitivity and specificity were 0.827 and 0.852, respectively, at the optimal cutoff value of 23.9 hours. This was followed by IG% (AUC = 0.712), with an optimal critical value of 0.55%, and a sensitivity of 0.519 and specificity of 0.797. All the AUC values of IG#, CRP, NE%, and NLR were <0.7. A combination of TTP with IG%, CRP, and NLR improved the AUC, sensitivity, specificity, accuracy, PPV, and NPV values to 0.977, 0.922, 0.957, 91.8%, 92.2%, and 91.3%, respectively. CONCLUSIONS: TTP within 24 hours indicates likelihood of CoNS as the pathogenic agent in pediatric patient blood culture. The combination of TTP with IG% CRP and NLR might improve the diagnostic accuracy.
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Bacteriemia/diagnóstico , Hemocultura , Proteína C-Reativa/análise , Contagem de Leucócitos , Infecções Estafilocócicas/diagnóstico , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Criança , Pré-Escolar , Feminino , Granulócitos/citologia , Humanos , Lactente , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus/patogenicidade , Fatores de TempoRESUMO
BACKGROUND: Kawasaki disease (KD), which is characterized by vasculitis, is prone to occur in patients under 5 years of age, has an ambiguous etiology, and displays coronary artery lesions as the chief complication. Previous studies have linked miRNA-149 to cancers, and rs2292832 T>C is related to allergic diseases and inflammatory bowel disease, which both show immune system disorders and coronary artery disease. Therefore, we performed a study concentrating on the association between the miRNA-149 rs2292832 T>C polymorphism and KD susceptibility. METHODS: The subjects enrolled were 532 children with KD and 623 controls. We used TaqMan real-time PCR to obtain the genotypes of the rs2292832 T>C polymorphism. RESULTS: Ultimately, no significant association was found between the miRNA-149 rs2292832 T>C polymorphism and KD susceptibility, even in stratification analysis. CONCLUSION: Our results indicated that in southern Chinese patients, the miRNA-149 rs2292832 T>C polymorphism did not affect KD susceptibility, which needs to be further confirmed.
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MicroRNAs/genética , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo de Nucleotídeo Único , Povo Asiático/genética , Estudos de Casos e Controles , Pré-Escolar , Frequência do Gene , Predisposição Genética para Doença , HumanosRESUMO
BACKGROUND: miRNAs play important roles in a variety of diseases. Thus, the association between miRNA-196a2 rs11614913 T>C polymorphism and Kawasaki disease susceptibility is still unknown. METHODS: We included 532 children with Kawasaki disease and 623 healthy children from South China, and their DNA was extracted for genotyping by TaqMan methodology. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of association. RESULTS: No significant associations were observed between the miRNA-196a2 rs11614913 T>C polymorphisms and Kawasaki disease risk (TC vs TT: adjusted OR = 1.04, 95% CI = 0.79-1.37; CC vs TT: adjusted OR = 0.87, 95% CI = 0.63-1.21; dominant model: adjusted OR = 0.99, 95% CI = 0.76-1.27; and recessive model: adjusted OR = 0.85, 95% CI = 0.64-1.13). There was also no significant correlation found in stratified analyses. CONCLUSION: This study suggests that miRNA-196a2 rs11614913 T>C may not be associated with Kawasaki disease susceptibility in a southern Chinese population. Larger, multicenter studies are needed to confirm our conclusions.
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Povo Asiático/genética , Estudos de Associação Genética , Predisposição Genética para Doença , MicroRNAs/genética , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo de Nucleotídeo Único/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , MicroRNAs/metabolismoRESUMO
GATA zinc finger domain-containing 2B (GATAD2B) is a subunit of the methyl-CpG-binding protein-1 complex (MECP1), which deacetylates methylated nucleosomes and regresses transcriptional activity. Recently, GATAD2B has been elucidated as a candidate gene in patients with intellectual disability (ID). In this study, we identified two novel heterozygous frameshift mutations of GATAD2B in two unrelated ID cases through next-generation sequencing (NGS). Both of the mutations c.80_81insGATGT and c.552_555delGAAA cause truncated proteins that might be detrimental to neurodevelopment. We performed western blotting and observed a reduction in the target protein compared with normal controls. This is the first report of GATAD2B in Chinese ID patients. Our findings will broaden the spectrum of GATAD2B mutations and facilitate genetic diagnosis and counseling.
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Fatores de Transcrição GATA/genética , Estudos de Associação Genética , Deficiência Intelectual/genética , Criança , Pré-Escolar , Feminino , Mutação da Fase de Leitura , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Deficiência Intelectual/patologia , Masculino , Proteínas RepressorasRESUMO
POGZ, the gene encoding pogo transposable element-derived protein with zinc-finger domain, has been implicated in autism spectrum disorder and it is widely expressed in the human tissues, including the brain. Intellectual disability (ID) is highly heterogeneous neurodevelopment disorder and affects ~2-3% of the general population. Here we report the identification of a novel frameshift mutation in the coding region of the POGZ gene (c.1277_1278insC), which occurred de novo in a Chinese patient with ID. In silico analysis and western blotting revealed this frameshift mutation generating truncated protein in peripheral blood lymphocytes, and this may disrupt several important domains of POGZ gene. Our finding broadens the spectrum of POGZ mutations and may help to understand the molecular basis of ID and aid genetic counseling.
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Transtorno do Espectro Autista/genética , Mutação da Fase de Leitura/genética , Deficiência Intelectual/genética , Transposases/genética , Transtorno do Espectro Autista/patologia , Criança , Exoma/genética , Feminino , Humanos , Deficiência Intelectual/patologiaRESUMO
BACKGROUND: Cilia play an important role in cellular signaling pathways. Defective ciliary function causes a variety of disorders involve retina, skeleton, liver, kidney or others. Cilia-related kidney disorders are characterized by cystic renal disease, nephronophthisis and renal failure in general. METHODS: In this study, we collected 33 families clinically suspected of cilia-related kidney disorders. Capture-based next-generation sequencing (NGS) of 88 related genes, Sanger sequencing, pedigree analysis and functional study were performed to analyze their genetic cause. RESULTS: 40 mutations in PKD1, PKD2, PKHD1, DYNC2H1 and TMEM67 genes were identified from 27 of 33 affected families. 70% (28/40) of the mutations were first found in patients. We reported a very early-onset autosomal dominant polycystic kidney disease (ADPKD) family caused by a novel heterozygous PKD1 mutation; another fetus with DYNC2H1 compound heterozygous missense mutations showed mainly kidney dysplasia instead of skeletal abnormalities; and a novel PKD1 mutation, c.12445-3Câ¯>â¯G, was confirmed to cause two wrong splicing modes. As for previously reported mutations, such as PKD1, c.6395â¯Tâ¯>â¯G (p.F2132C) and c.6868Gâ¯>â¯T (p.D2290Y), we had new and different findings. CONCLUSION: The findings provided new references for genotype-phenotype analyses and broadened the mutation spectrum of detected genes, which were significantly valuable for prenatal diagnosis and genetic counseling.
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Doenças Renais Císticas/genética , Mutação , Insuficiência Renal/genética , Adulto , Pré-Escolar , China , Dineínas do Citoplasma/sangue , Dineínas do Citoplasma/genética , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Doenças Renais Císticas/sangue , Masculino , Proteínas de Membrana/sangue , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Fenótipo , Gravidez , Receptores de Superfície Celular/sangue , Receptores de Superfície Celular/genética , Insuficiência Renal/sangue , Canais de Cátion TRPP/sangue , Canais de Cátion TRPP/genética , Adulto JovemRESUMO
Giant axonal neuropathy (GAN) is a rare and grievous autosomal recessive neurodegenerative disease due to loss-of-function mutation in GAN. However, the chimerism of complex rearrangement sequences of GAN has not been reported so far, and the mechanism for its complex rearrangements remains to be determined. We identified a family with clinical symptoms of GAN and aimed to reveal a genetic cause underlying this disease. By whole-exome sequencing in the patient we identified a novel homozygous frameshift mutation with 1 bp deletion (c.27delC) in GAN. However, when analyzed the patient's genomic DNA (gDNA) by quantitative real-time PCR and breakpoint DNA sequencing, we found the chimerism of multiple complex rearrangement sequences encompassing exon 1 of GAN in the patient's genome. The microhomology and localization of the breakpoint indicated that they may be caused by Alu repeat elements. We also found that the mRNA expression level of GAN in patient's lymphocyte was decreased, confirming the pathogenicity of these mutations. Our study is the first reported on many complex rearrangement sequences mosaic in GAN mediated by Alu element. The patient here is not a simple homozygous frameshift mutation, but a compound heterozygous paternal c.27delC mutation and the chimerism of multiple de novo complex rearrangement sequences in GAN. Our results may also provide new insights into the formation and pathogenicity of complex rearrangement in GAN, and may be helpful to genetic counseling and genetic testing. It also enriches the Alu-mediated disease-associated database which are important for correct clinical interpretation.
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Elementos Alu/genética , Neuropatia Axonal Gigante/genética , Criança , Quimerismo , DNA/genética , Humanos , Masculino , Mutação , Reação em Cadeia da PolimeraseRESUMO
Fluoroquinolone (FQ)-resistant Group B Streptococcus (GBS) has been reported with considerable cross-resistance, worsening the crisis of multidrug-resistant (MDR) GBS in clinical settings. However, national epidemiological data on FQ-resistant GBS in mainland China have not been well-characterized. This study aimed to determine the prevalence of FQ resistance among GBS from neonatal invasive infections and maternal colonization in northern and southern China, to investigate the serotyping, multilocus sequence typing, and antibiotic cross-resistance, and to characterize the mutations in gyrA and parC genes in quinolone resistance-determining region (QRDR). In order to provide a comprehensive view of the location and structure of resistance genes, whole-genome sequencing on III/ST19 MDR isolates were performed. Among 426 GBS, 138 (32.4%) were FQ resistant, with higher prevalence in northern China than in southern China in both neonates (57.8%, 37/64 vs. 21.7%, 39/180) and pregnant women (50.9%, 29/57 vs. 26.4%, 33/125). Serotypes were distributed as III (48.5%), Ib (39.9%), V (6.5%), and Ia (5.1%). Sequence types were mainly ST19 (53.6%) and ST10 (39.1%), followed by ST12 (1.4%), ST17 (1.4%), ST23 (1.4%), and 0.7% each of ST27, ST188, ST197, and ST597. ST19 isolates were more prevalent in southern China than in northern China in both neonates (64.1%, 25/39 vs. 27.0%, 10/37) and pregnant women (81.8%, 27/33 vs. 41.4%, 12/29), whereas ST10 isolates were more common in northern China than in southern China in both neonates (64.9%, 24/37 vs. 20.5%, 8/39) and pregnant women (58.6%, 17/29 vs. 15.2%, 5/33). Serotype III isolates were mainly ST19 (89.6%, 60/67), while Ib isolates were largely ST10 (94.5%, 52/55). Sequencing data revealed several mutations in QRDR, including Ser81Leu in gyrA (99.2%, 130/131), Ser79Phe or Tyr in parC (76.2%, 48/63), and a previously unreported Ile218Thr and Ile219Phe double mutation pattern (49.2%, 31/63) in parC. ST10 isolates were associated with Ser79Phe (84%, 21/25), while ST19 isolates were limited to Ser79Tyr (95.7%, 22/23). A new integrative and conjugative element (ICE) harboring tetM and gyrA genes was identified in a III/ST19 isolate. This study investigates the molecular characteristics of FQ-resistant GBS in northern and southern China, emphasizing the need for continuous surveillance geographically and further research to characterize the mechanisms of ICE transfer.
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Children with Kawasaki disease (KD) resistant to intravenous immunoglobulin (IVIG) have a higher incidence of coronary artery lesions (CAL). Despite the association between Purinergic receptor P2Y12 (P2RY12) polymorphism, KD genetic susceptibility, and CAL complications being proved, few studies have assessed the relationship between P2RY12 polymorphisms and IVIG resistance in patients with KD. We recruited 148 KD patients with IVIG resistance and 611 with IVIG sensitivity and selected five P2RY12 polymorphisms: rs9859538, rs1491974, rs7637803, rs6809699, and rs2046934. A significant difference in the genotype distributions between patients was only observed for the rs6809699 A > C polymorphism (AC vs. AA: adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.27-0.84, P=0.011; AC/CC vs. AA: adjusted OR = 0.47, 95% CI = 0.27-0.83, P=0.0084). After adjusting for age and gender, the carriers of the rs6809699 C allele had OR of 0.44 to 0.49 for IVIG sensitivity (AC vs. AA: adjusted OR = 0.48, 95% confidence interval (CI) = 0.27-0.84, P=0.011; AC/CC vs. AA: adjusted OR = 0.47, 95% CI = 0.27-0.83, P=0.0084) compared to the carriers of a rs6809699 AA genotype, suggesting the protective effect of this SNP against IVIG resistance. Moreover, individuals with all five protective polymorphisms experienced a significantly decreased IVIG resistance compared to that of individuals with up to three protective polymorphisms (adjusted OR = 0.27, 95% CI = 0.13-0.57, P=0.0006). Our results suggest that the P2RY12 rs6809699 polymorphism could be used as a biomarker to predict IVIG resistance in KD patients.
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Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/prevenção & controle , Resistência a Medicamentos/genética , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Receptores Purinérgicos P2Y12/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Tomada de Decisão Clínica , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/imunologia , Feminino , Frequência do Gene , Heterozigoto , Homozigoto , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/imunologia , Seleção de Pacientes , Testes Farmacogenômicos , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
Oculocutaneous albinism is an autosomal recessive disorder characterized by either a complete lack of or reduction in melanin biosynthesis in the skin, hair, and eyes. The aim of the present study was to identify the molecular basis for 59 Chinese OCA families. In this study, compound heterozygous or homozygous pathogenic variants were found in 53 families, 4 families possessed only one heterozygous variant, and the pathogenic variants of 2 families remain undiscovered by using Sanger sequencing, whole exome sequencing and multiplex ligation-dependent probe amplification. We have identified a total of 55 variants including 21 novel variants in TYR, OCA2, SLC45A2, SLC24A5, and HPS1. The 21 novel variants include 11 missense changes, 4 nonsense changes, 2 splice site changes, 1 frameshift and 3 gross deletions. Forty-six variants including 14 novel variants were segregated with the phenotype in 37 families. We conducted RT-PCR of the novel splicing site variant (c.399-14Gâ¯>â¯A) of HPS1 and verified that the variant would result in the inclusion of 12 bp of intronic material in exon 6 of HPS1. The results of platelet whole mount electron microscopy further confirmed the diagnosis of HPS1. These novel variants identified in our study expand the mutational spectrum of the disease, which contributes to prenatal diagnosis and genetic counselling.
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Albinismo Oculocutâneo/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Adolescente , Adulto , Alelos , Povo Asiático , Criança , Pré-Escolar , China , Biologia Computacional/métodos , Exoma , Feminino , Estudos de Associação Genética/métodos , Genótipo , Humanos , Lactente , Masculino , Mutação , Prevalência , Fluxo de Trabalho , Adulto JovemRESUMO
BACKGROUND: Neonatal sepsis (NS) is one of the leading causes of infant morbidity and mortality, but little is known about pathogen incidence and distribution in China. METHODS: In this retrospective study (January 2012 to December 2016), culture-proven cases aged less than 28 days with diagnosed NS in the Guangzhou Women and Children's Medical Center, South China, were analyzed for pathogen incidence and antimicrobial resistance. RESULTS: A total of 620 isolates were identified from 597 NS cases. Gram-negative bacteria (n=371, 59.8%) dominated over Gram-positive bacteria (n=218, 35.2%) and fungi (n=30, 4.8%). Klebsiella pneumoniae (21.9%), Escherichia coli (21.9%), group B Streptococcus (GBS, 13.2%), and Staphylococcus aureus (6.8%) were the four most predominant pathogens. In early-onset sepsis (EOS), GBS (30.0%) and E. coli (20.0%) were dominant, whereas in late-onset sepsis (LOS), K. pneumoniae (25.6%) and E. coli (22.4%) were dominant. E. coli (25.2%) and GBS (17.7%) were the most frequently isolated from term patients, whereas K. pneumoniae was the most frequently isolated from preterm patients (34.9%). Of the infected infants, 9.5% died from sepsis, most commonly by E. coli infection (16.2%). Among 91,215 live births (LBs) delivered in the study hospital (2012-2016), 252 infants developed sepsis infection (2.76 per 1000 LBs, 95% CI 2.4-3.1), including EOS (0.78 per 1000 LBs) and LOS (2.13 per 1000 LBs). All GBS isolates were susceptible to ß-lactam antibiotics, and S. aureus, including methicillin-resistant isolates, were susceptible to vancomycin. An extended-spectrum ß-lactamase producer was identified in 37.3% of E. coli and 50.4% of K. pneumoniae. CONCLUSION: K. pneumoniae was the most frequent pathogen in culture-proven NS in South China, primarily associated with LOS in preterm, whereas GBS was the dominant pathogen in EOS. E. coli was common in both episodes with the highest mortality.
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BACKGROUND: Kawasaki disease (KD) is an acute vasculitis disease that commonly causes acquired heart disease in children. Coronary artery aneurysm (CAA) is a major complication of KD. However, the pathogenesis of KD remains unclear. The results of a genome-wide association study (GWAS) showed that two functional single-nucleotide polymorphisms (SNPs; rs699A>G and rs5050T>G) in the angiotensinogen (AGT) gene were related to cardiovascular disease susceptibility. The purpose of our study was to estimate the relationship between the two GWAS-identified AGT gene polymorphisms and the risk of CAA in Southern Chinese children with KD. METHODS: We genotyped the two AGT gene polymorphisms (rs699A>G and rs5050T>G) in 760 KD cases and 972 healthy controls. We used the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the degree of the associations. RESULTS: These two AGT gene polymorphisms were not associated with a risk of KD relative to the controls, but after adjusting for sex and age, the carriers of the rs5050G allele with TG/GG vs TT had an adjusted OR = 1.56, 95% CI = 1.01-2.41, and P = 0.044 relative to the carriers of the rs5050TT genotype. The susceptibility to CAA was more predominant in KD patients younger than 12 months old. CONCLUSIONS: Our results indicate that the AGT gene polymorphism rs5050T>G may increase the risk of CAA in children with KD, especially those who are younger than 12 months. These results need to be verified by a validation study with a larger sample size.
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Angiotensinogênio/genética , Aneurisma Coronário/genética , Síndrome de Linfonodos Mucocutâneos/complicações , Polimorfismo de Nucleotídeo Único , Criança , Pré-Escolar , China , Aneurisma Coronário/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
BACKGROUND: A multidrug-resistant (MDR) RR2 gene cluster was identified by whole-genome sequencing in several highly virulent (ST-17) Group B streptococcus (GBS) isolates, which caused neonatal invasive infections in southern China in 2016. Tracing the transmission and distribution of MDR isolates in this area is important for the effective management of future infections. The aim of this study was to obtain longitudinal data of MDR isolates to monitor epidemiological trends of general common isolates in southern China, and provide evidence for future characterization of antimicrobial resistance mechanisms. METHODS: Clinical information and antimicrobial susceptibility of GBS isolates were acquired from electronic information management system databases of the hospital under study between January 2011 and December 2017. To confirm the presence of intact RR2, the tetO, ant6, lnuB, and ant9 genes located upstream, midstream, and downstream of RR2 were detected by PCR and DNA sequencing. RESULTS: A total of 149 cases of neonatal invasive GBS infection were identified during the period 2011-2017. Among them, 119 cases (79.9%) were caused by MDR isolates, with a general increasing trend over the past 7 years. Further characterization of 11 isolates showed that six isolates causing late-onset disease (LOD) carry the tetO, ant6, and lnuB genes, which are located on RR2. Moreover, lnuB and ant9 consistently co-occurred in GBS isolates, which suggests their close proximity to one another in the RR2 gene cluster. CONCLUSION: The MDR GBS is responsible for a large number of neonatal invasive infections and occurs with increasing frequency over time. Particularly, the MDR GBS isolates that cause LOD are more likely to carry the RR2 gene cluster, compared with those that cause early-onset disease. The rise in number of MDR GBS isolates emphasizes the pressing need for continuous surveillance to monitor their antibiotic susceptibility and epidemiology.
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Trauma remains a tremendous medical burden partly because of increased expenditure for the management of multiple organ dysfunction syndrome (MODS) developed during hospital stay. The intestinal barrier injury continues to be a second insult resulting in MODS which currently lacks efficient strategies for prevention. Recent studies have uncovered multi-organ protective benefits of atrial natriuretic peptide (ANP) in cardiovascular disease. However, the role of ANP in the prevention of MODS following severe trauma has not been understood. In our laboratory study, 1-h infusion of exogenous ANP during hemorrhagic shock following severe trauma induced high-level expression of endogenous serum ANP after 24âh, this effect was related to the improved level of functional biomarkers in multiple organs. Such phenomenon has not been found in other laboratories. A thorough literature review consequently was performed to uncover the potential mechanisms, to appraise therapy safety, and to propose uncertainties. In severe trauma, short-term exogenous ANP therapy during hemorrhagic shock may promote sustained endogenous expression of ANP from intestinal epithelium through activating a positive feedback loop mechanism involving phospholipase C-γ1 and reactive oxygen species crosstalk. This feedback loop may prevent MODS through multiple signaling pathways. Administration of ANP during hemorrhagic shock is thought to be safe. Further studies are required to confirm our proposed mechanisms and to investigate the dose, duration, and timing of ANP therapy in severe trauma.
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Fator Natriurético Atrial/sangue , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Ferimentos e Lesões/complicações , Fator Natriurético Atrial/uso terapêutico , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Humanos , Insuficiência de Múltiplos Órgãos/prevenção & controle , Choque Hemorrágico/sangue , Ferimentos e Lesões/sangueRESUMO
AIM: To discuss the the diagnostic value of fluorescence quantitative PCR in screening of influenza A virus. METHODS: Influenza A virus RNA in 150 cases of suspected influenza patients with throat swab was measured by fluorescence quantitative RT-PCR. The white blood cell count was measured by XT-1800 automated hematology analyzer in patients' anticoagulant EDTA whole blood. 45 cases of influenza A virus RNA-positive patients were detected with influenza A virus core protein by colloidal gold. RESULTS: In 150 patients, 54 cases were detected influenza A virus RNA positive, the positive rate was 36%.The 54 cases of influenza A virus RNA-positive patients were detected with influenza A virus core protein by colloidal gold, the results were all negative.The white blood cell count is (6.81+/-2.12) x 10(9)/L in the influenza A virus RNA-positive patients, and (6.64+/-3.13) x 10(9)/L for the negative cases. White blood cell count in patients with influenza A and non-influenza patients have no significant difference. CONCLUSION: Fluorescence quantitative RT-PCR in the detection of influenza A virus RNA has a better positive rate, its sensitivity and specificity are better than colloidal gold and white blood cell count, and it can be screened quickly and efficiently in patients with influenza to prevent disease outbreaks.
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Vírus da Influenza A/isolamento & purificação , Influenza Humana/diagnóstico , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Vírus da Influenza A/genética , Influenza Humana/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Espectrometria de Fluorescência , Proteínas do Core Viral/análise , Adulto JovemRESUMO
OBJECTIVE: To study the change of special antibodies titer IgG, IgM and nucleocapsid to SARS coronavirus (CoV) and observing the expression of stomach and enteric involvement on SARS-CoV infection by monoclonal antibody against N protein of SARS-CoV in the 7-year recovery period among family clustering cases of severe acute respiratory syndrome. METHODS: Special antibody titer to SARS-CoV of 14 patients from 5 different families and their 10 kinfolks continuously tested by IFA and antigen-capturing ELISA methods. Samples were taken in the 1(st) - 7(th) year periods after SARS patients infected by SARS-CoV, being diluted and measured on it titers of three kinds of antibodies. Immunochemical staining with monoclonal antibody (mAb) against N protein of SARS-CoV was used to determine the stomach and enteric tissues among 5 SARS patients with their nucleocapsid antibody titer ascended obviously after 1(st)-7(th) year. RESULTS: When testing the IgG antibody titer of the 14 SARS patients by IFA method, the average titer was 1/71 (95%CI: 1/58 - 1/85) in the 1(st) year, but began to descend in the following years, and the IgG antibody of the most SARS patients disappeared in the 7(th) year. Regarding the IgM titer, it disappeared in most of the SARS patients 1 year later. The average value of nucleocapsid antibody titer was 1/146 (95%CI: 1/122 - 1/171) in the 1(st) year, and it descended as the IgG antibody titer did. In 5 cases, differences appeared. The nucleocapsid antibody titer was between 1/156 and 1/210 in 3 cases, and 2 cases were normal. Immunochemical staining with mAb against N protein of SARS-CoV was identified in the stomach and enteric tissues of 5 SARS patients with the nucleocapsid antibody titer increased significantly, 1(st)-7(th) year later. The five patients were detected by gastroscopy detection and cell immunohistochemistry test. 3 cases showed N protein antibody positive in the serum, and positive immunohistochemical expression in most of the cytoplasm in the gastric tissue mucous gland epithelial cells. 1 case also expressed in the intestinal tissue slurry columnar epithelium and interstitial cells. The other two cases showed negative on both serum N protein antibody and immunohistochemical expression. The biopsy results of the 5 patients were as follows: 1 case diagnosed as "signet-ring cell carcinoma of the stomach and rectum multiple transfer", 1 case of gastric polyp, 1 case of superficial antral gastritis and 2 cases were normal. CONCLUSION: By testing the special IgG, IgM, nucleocapsid antibody to SARS-CoV of the 14 family clustering cases, we found that they all decreased in the 7(th) year, and most of them disappeared. The nucleocapsid antibody titer was related to pathogenetic condition. SARS-CoV was proved to be still present in stomach and enteric tissues of SARS patients with the nucleocapsid antibody titer increased significantly after the 7(th) year.