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BACKGROUND: Enterovirus (EV) infections are being increasingly seen in younger infants, often being more severe than in older children. The risk factors of EV infection in infants have been inadequately investigated till date. METHODS: We conducted a retrospective study on hospitalized children with laboratory-confirmed EV infection (50 infants aged 0-3 months and 65 older than 3 months) at a tertiary care center in China. Prevalence, clinical characteristics, and genetic features of the virus were analyzed, and independent predictors for severe infection were assessed. RESULTS: Clinical findings showed that severe infection was more common in infants aged 0-3 months than in older children (78.0% vs. 35.4%, p < 0.001), with higher morbidity of pneumonia, meningitis, and sepsis (p < 0.01). EV-B types were detected more frequently in infants aged 0-3 months than in older children (88.0% vs. 7.7%, p < 0.001). Echovirus 11 was the most identified EV-B, and it recombined with E6 in P2 and P3 regions. Risk factors for severe EV infection included EV-B types infection, age less than 3 months, elevated alanine aminotransferase level, abnormal platelet count, and abnormal cerebrospinal fluid characteristics. CONCLUSIONS: Our data indicated that EV-B types mainly cause severe infection in infants aged 0-3 months. Therefore, knowledge about EV-B types could have implications in designing effective intervention and prevention strategies for young infants with severe EV infection.
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Infecções por Enterovirus , Enterovirus , Parechovirus , Infecções por Picornaviridae , Humanos , Lactente , Enterovirus/genética , Enterovirus Humano B , Infecções por Enterovirus/epidemiologia , Parechovirus/genética , Estudos RetrospectivosRESUMO
BACKGROUND: Identifying sarcopenia's causally associated plasma proteins would provide potential therapeutic targets. METHODS: We screened out sarcopenia-related proteins with genome-wide association studies (GWAS) summary data and cis-protein loci genetic instruments. Summary data of sarcopenia were obtained from a GWAS of 256,523 Europeans aged 60 years and over. The causal effects of the proteins were investigated by cis-Mendelian Randomisation (MR) and multiverse sensitivity analysis. We also explored the robust proteins' causal associations with appendicular lean mass (ALM) and surveyed their druggability and clinical development activities. RESULTS: In sum, 60 proteins from plasma proteome analysis studies and 12 from other studies were enrolled for MR analysis. In the whole population, four proteins (HPT, AT1B2, ISLR2 and TNF12) showed causal associations with the risk of sarcopenia according to the European Working Group on Sarcopenia in Older People (EWGSOP) criterion. In the female population, AT1B2 and TNFSF12 revealed causal associations with sarcopenia risk according to the EWGSOP criterion; HGF revealed a negative association according to the National Institutes of Health criterion. All of them were druggable, and the inhibitors of TNF12 and HGF were evaluated in clinical trials for other diseases. TNF12 also revealed a negative causal association with ALM, whereas HGF was positively causally associated with ALM. CONCLUSIONS: Five druggable plasma proteins revealed causal associations with sarcopenia in the whole or female populations. TNF12 and HGF were the targets of therapeutic agents evaluated in clinical trials, and they were also causally associated with ALM. Our study suggested the potential mechanisms and therapeutic targets for sarcopenia.
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Sarcopenia , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Sarcopenia/diagnóstico , Sarcopenia/tratamento farmacológico , Sarcopenia/genética , Estudo de Associação Genômica Ampla , Composição Corporal , Inquéritos e Questionários , Proteínas SanguíneasRESUMO
BACKGROUND: With better patient selection and the increasing experience in patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) combined surgery, the rate of severe postoperative complications and mortality decreased significantly. However, leukopenia and neutropenia were still a particular concern, and their relation to sarcopenia was not clarified. METHODS: Data of consecutive patients who underwent HIPEC for gastrointestinal cancer were collected and analyzed retrospectively between September 2020 and August 2022. Sarcopenia was assessed using psoas muscle index (PMI) at the L3 level on preoperative computed tomography (CT). RESULTS: Among 103 patients enrolled, 37 (35.9%) were classified as sarcopenic. Most leukopenia and neutropenia occurred during the hospital leaving period after HIPEC and surgery. Before the first time of postoperative chemotherapy, the blood tests revealed 11 (29.73%) and 6 (9.09%) patients were diagnosed with neutropenia in sarcopenia and no sarcopenia groups, respectively. Logistic regression analysis revealed sarcopenia was independently associated with the increased risk of neutropenia (OR 5.58, 95% CI 1.70-18.29, p = 0.005). An incremental albumin level was protective against the occurrence of leukopenia and neutropenia. CONCLUSIONS: Sarcopenia and low albumin level were significantly associated with an increased rate of delayed neutropenia after HIPEC in that disease setting and could be the preoperative risk predictors.
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Neoplasias Gastrointestinais , Hipertermia Induzida , Neutropenia , Sarcopenia , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Sarcopenia/etiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Albuminas , Procedimentos Cirúrgicos de Citorredução/efeitos adversosRESUMO
BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common infectious disease occurring in children under 5 years of age worldwide, and Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CVA-16) are identified as the predominant pathogens. In recent years, Coxsackievirus A6 (CVA-6) and Coxsackievirus A10 (CVA-10) have played more and more important role in a series of HFMD outbreaks. This study aimed to understand the epidemic characteristics associated with HFMD outbreak in Guangzhou, 2018. METHODS: The clinical and laboratory data of 1220 enterovirus-associated HFMD patients in 2018 were analysed in this study. Molecular diagnostic methods were performed to identify its serotypes. Phylogenetic analyses were depicted based on the complete VP1 gene. RESULTS: There were 21 enterovirus serotypes detected in Guangzhou in 2018. Three serotypes of enterovirus, CVA-6 (364/1220, 29.8%), CVA-10 (305/1220, 25.0%), and CVA-16 (397/1220, 32.5%), were identified as the causative pathogens and accounted for 87.3% among all 1220 HFMD patients. In different seasons, CVA-6 was the predominant pathogen of HFMD during autumn, and CVA-10 as well as CVA-16 were more prevalent in summer. Patients infected by CVA-6, CVA-10 or CVA-16 showed similar clinical features and laboratory characteristics, and the ratios of severe HFMD were 5.8, 5.9, and 1.5% in the three serotypes. Phylogenetic analyses of VP1 sequences showed that the CVA-6, CVA-10, and CVA-16 sequences belonged to the sub-genogroup E2, genogroup E, and genogroup B1, respectively. CONCLUSIONS: CVA-6, CVA-10, and CVA-16 were the predominant and co-circulated serotypes in Guangzhou China, 2018, which should be the new target for prevention and control of HFMD. Our findings provide useful information for diagnosis, treatment, and prevention of HFMD.
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Enterovirus Humano A/classificação , Enterovirus Humano A/genética , Epidemias , Doença de Mão, Pé e Boca/epidemiologia , Sequência de Bases/genética , Proteínas do Capsídeo/genética , Criança , Pré-Escolar , China/epidemiologia , Feminino , Genótipo , Doença de Mão, Pé e Boca/virologia , Humanos , Lactente , Masculino , Filogenia , Prevalência , Estações do Ano , SorogrupoRESUMO
OBJECTIVE: To study the distribution of peripheral blood lymphocyte subsets in healthy children aged 0-6 years. METHODS: A total of 826 healthy Han children aged 0-6 years were recruited. According to their age, the children were divided into four groups: newborn, infant, toddler and preschool. Their peripheral blood samples were collected to measure the percentages of lymphocyte subsets by flow cytometry. RESULTS: There were significant differences in the percentages of CD3+ T cells, CD3+CD4+ T cells and CD3-CD19+ B cells and the CD4+/CD8+ ratio between boys and girls (P<0.05). The girls had a lower percentage of CD3-CD19+ B cells, higher percentages of CD3+ T cells and CD3+CD4+ T cells and a higher CD4+/CD8+ ratio than the boys. The newborn group had the highest percentages of CD3+ T cells and CD3+CD4+ T cells and the highest CD4+/CD8+ ratio (P<0.05). The percentage of CD3+CD4+ T cells and the CD4+/CD8+ ratio gradually decreased with age and the preschool group had the lowest values (P<0.05). The newborn group had the lowest percentages of CD3-CD19+ B cells and CD3-CD16+CD56+ NK cells (P<0.05). The percentage of CD3-CD16+CD56+ NK cells gradually increased with age and the preschool group had the highest percentage (P<0.05). The percentage of CD3-CD19+ B cells reached the peak in the toddler period and then decreased with age (P<0.05). The preschool group had the highest percentage of CD3+CD8+ T cells (P<0.05). The variation trend of distribution of lymphocyte subsets in boys from different age groups was consistent with that in children from different age groups. For girls, the newborn group had the highest percentage of CD3+CD4+ T cells and CD4+/CD8+ ratio (P<0.05). CONCLUSIONS: The distribution of peripheral blood lymphocyte subsets in healthy children is significantly different across ages and sexes. Therefore, the reference values should be established according to age and sex.
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Linfócitos B , Subpopulações de Linfócitos , Antígenos CD19 , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Lactente , Recém-Nascido , Células Matadoras Naturais , Contagem de Linfócitos , MasculinoRESUMO
OBJECTIVES: To report our institutional experience in the management of adult genitourinary sarcoma. METHODS: This was a retrospective analysis of data on adult genitourinary sarcoma treated at the West China Hospital, Sichuan University, Chengdu, Sichuan, China from 1985 to 2010. Clinicopathological parameters were analyzed to determine their impact on overall, recurrence-free and metastasis-free survivals. RESULTS: A total of 46 women and 142 men were included, with a median age of 42 years. Of these, 152 cases were high-grade. The most common site was the paratesticular region. Surgical resection was carried out in 155 patients (82.4%), with negative margin in 106. After a minimum follow up of 5 years, 20 patients (11.6%) survived disease-free, 14 (8.1%) were alive with disease and 138 (80.2%) died of disease. Survival rates at 1, 3 and 5 years were 91.3%, 64.0% and 47.7%. In univariate analyses, liposarcoma, high grade, metastasis at diagnosis, a lack of surgical resection and positive margin were predictive of unfavorable survival. In multivariate analyses, high grade, a lack of surgical resection and chemotherapy were independent predictors of poor survival. CONCLUSIONS: Adult genitourinary sarcoma is an aggressive malignancy, usually presenting at advanced stage, with a high incidence of recurrence and metastasis. Complete resection and selective combination of chemotherapy and radiotherapy might constitute the optimal treatment for this disease.
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Sarcoma/mortalidade , Neoplasias Urogenitais/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoma/diagnóstico , Sarcoma/patologia , Análise de Sobrevida , Neoplasias Urogenitais/diagnóstico , Neoplasias Urogenitais/patologia , Adulto JovemRESUMO
The objective of this paper was to evaluate the overall accuracy of elastography in the diagnosis of benign and malignant liver lesions by liver biopsy as the gold standard. Literature databases were searched. The studies which were related to evaluate the diagnostic value of elastography for differentiation in benign and malignant liver lesions in English or Chinese were included. The summary receiver operating characteristic (SROC) curve was performed, and the areas under the curve (AUC) were also calculated to present the accuracy of the elastography for the diagnosis of benign and malignant liver lesions. Six studies which included a total of 448 liver lesions in 384 patients were analyzed. The summary sensitivity and specificity of elastography for the differentiation of malignant liver lesions were 85% (95% CI, 80 to 89%) and 84% (95% CI, 80 to 88%), respectively. And the summary diagnostic odds ratio was 46.33 (95% CI, 15.22 to 141.02), and the SROC was 0.9328. Elastography has a high sensitivity and specificity differentiation for benign and malignant liver lesions. As a non-invasive method, it is promising to be applied to clinical practice. To estimate elastography objectively, a large, prospective, international, and multi-center study is still needed.
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Técnicas de Imagem por Elasticidade/métodos , Neoplasias Hepáticas/diagnóstico , Diagnóstico Diferencial , Humanos , Viés de Publicação , Curva ROC , Inquéritos e QuestionáriosRESUMO
Programmed death ligand 1 (PD-L1) is widely expressed in human tumors. It is widely known for its immunosuppressive function as it can help tumor cells evade T cell immune killing through the PD-1/PD-L1 signal. A number of clinical trials have proved that the destruction of the combination of PD-1 and PD-L1 by antibodies could significantly affect patients with advanced cancer. However, a number of patients with cancer still cannot benefit from PD-1/PD-L1 blocking therapy. The main reason is that PD-L1 also has some intrinsic regulatory functions to promote the progression of tumors. PD-L1 Protein contains an intrinsic domain that could link to other signal pathways, but the mechanism has not yet been fully revealed. The present review mainly discussed the non-immune checkpoint functions of PD-L1, such as its role in regulating cell proliferation, cell metabolism, drug resistance and maintaining epithelial-mesenchymal transition and stemness.
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Genogroup II genotype 4 (GII.4) norovirus causes acute gastroenteritis in children, and its infection is more severe than that of other genotypes. Early and precise detection and treatment are critical for controlling its spread and reducing the severity of infection. In this study, a rapid and efficient isothermal assay for the GII.4 norovirus detection (GII.4-CRISPR detection) was developed based on the CRISPR/Cas13a system. The assay can be applied without expensive instrumentation, and the results can be read via both fluorescence and lateral flow strip (LFS). The analytical sensitivity of this assay was 5 copies/reaction, and there was no cross-reaction with other genotypes of norovirus or other clinically common pathogens. There was a coincidence rate of 100% between our assay and commercial quantitative polymerase chain reaction. GII.4-CRISPR detection improves upon the shortcomings of some previously established molecular methods of detection, particularly with regard to accessibility. It provides an alternative tool for outbreak control and early diagnosis of GII.4 norovirus infection.
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BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition characterized by abundant IgG4 positive plasma cells and fibrosis in the affected tissues. It affects most parts of the body; however, there are not many reports on IgG4-RD involving the colon. CASE SUMMARY: A 50-year-old man complaining of intermittent fever for more than two years was referred to our hospital. Based on various investigations before surgery, we diagnosed him with chronic perforation of the sigmoid colon caused by inflammatory change or tumor. IgG blood tests before the operation suggested IgG4-RD, and postoperative pathology confirmed this prediction. CONCLUSION: We present a patient with IgG4-RD with colon involvement, which is an uncommon site. This report will expand the understanding of IgG4-RD in unknown tissues.
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BACKGROUND: Genital Chlamydia trachomatis (CT) is one of the most common agents of sexually transmitted infections and can cause severe disorders. This study aimed to analyse the genetic and clinical characteristics of genital CT infection among women in Guangzhou, China. METHODS: From September 2020 to August 2021, a total of 8955 female patients were enrolled in this study. The presence of genital CT was detected by real-time PCR, and 273 positive samples were randomly selected for further genetic and clinical characteristics analysis. RESULTS: The positive rate of genital CT infection was 7.5% (670/8955), with the highest rate in women aged 21-30 years. A total of 8 genotypes were identified: DH, J, K, and recombinant genotype Ba/D. The predominant genotype was J (n = 78, 28.6%), followed by E (n = 63, 23.1%), F (n = 48, 17.6%), and D (n = 38, 13.9%). Abnormal vaginal discharge (n = 165, 61.8%), cervical columnar epithelial ectopy (n = 124, 46.4%), vaginal itching (n = 77, 28.8%), and lower abdominal pain (n = 61, 22.8%) were the predominant symptoms. Additionally, genotype G infection exhibited a significantly higher rate of abnormal vaginal discharge (P = 0.03) and genotype D infection exhibited a higher white blood cell count (P = 0.01) than the other genotypes. Phylogenetic analysis revealed a total of 20 variants with 25 mutation positions and the H2 variant in four patients was first discovered in our study. CONCLUSIONS: Genotypes J, E, F, and D were the major genotypes of genital CT in Guangzhou, and they manifested as abnormal vaginal discharge, cervical columnar epithelial ectopy, vaginal itching, and lower abdominal pain. The present study provides guidance for future integrated interventions to reduce the burden of genital CT infection and accelerate the development of vaccines.
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Infecções por Chlamydia , Descarga Vaginal , Dor Abdominal , Adulto , China/epidemiologia , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis/genética , Feminino , Genitália , Humanos , Filogenia , Prurido , Adulto JovemRESUMO
This study is aimed at exploring the potential role of GSDMC in kidney renal clear cell carcinoma (KIRC). We analyzed the expression of GSDMC in 33 types of cancers in TCGA database. The results showed that the expression of GSDMC was upregulated in most cancers. We found a significant association between high expression of GSDMC and shortened patient overall survival, progression-free survival, and disease-specific survival. In vitro experiments have shown that the expression of GSDMC was significantly elevated in KIRC cell lines. Moreover, decreased expression of GSDMC was significantly associated with decreased cell proliferation. In summary, we believe that this study provides valuable data supporting future clinical treatment.
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Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Proteínas de Ligação a DNA/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/fisiologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , China , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/fisiologia , Bases de Dados Genéticas , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Rim/patologia , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Transdução de Sinais/genética , Ativação Transcricional/genética , Transcriptoma/genéticaRESUMO
Norovirus, the leading cause of non-bacterial acute gastroenteritis (AGE) worldwide, is constantly mutating. Continuous monitoring of the evolution of epidemic genotypes and emergence of novel genotypes is, therefore, necessary. This study determined the prevalence and clinical characteristics of norovirus strains in AGE in Guangzhou, China in 2019/2020 season. This study included children aged 2-60 months diagnosed with AGE in Guangzhou Women and Children Hospital, from August 2019 to January 2020. Norovirus was detected by real-time polymerase chain reaction and clinical data were obtained. Genotyping and phylogenetic analyses were performed with partial gene sequence fragments located within the open reading frames 1 and 2. During the study period, 168 children (61.3% males) were confirmed as norovirus infectious AGE. The main symptoms were diarrhoea and vomiting and 38 patients (22.6%) had seizures. Norovirus was mainly prevalent in October and November, and GII.4 Sydney[P31] was the major genotype circulating in Guangzhou. The phylogenetic tree showed that the Guangzhou strains had high homology with the strains circulating in 2017-2019 worldwide. GII.4 Sydney was the main prevalent norovirus genotype in Guangzhou from August 2019 to January 2020, which had more severe diarrhoea than those of other genotypes. These findings provide a valuable reference for the prevention, control, and treatment of norovirus in the future.
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Infecções por Caliciviridae , Gastroenterite , Norovirus , Infecções por Caliciviridae/epidemiologia , Criança , China/epidemiologia , Fezes , Feminino , Gastroenterite/epidemiologia , Genótipo , Humanos , Masculino , Norovirus/genética , Filogenia , Prevalência , RNA Viral , Estações do AnoRESUMO
The aim of this study was to retrospectively compare hematological parameters among normal, α-, and ß-thalassemia fetuses between 17 and 38 weeks of gestation. Pregnant women at risk of having fetuses with thalassemia major and underwent cordocentesis for prenatal diagnosis were recruited. Fetal cord blood samples were collected from 249 fetuses for hematological and DNA analysis. Fetuses were divided into subgroups according to thalassemia DNA genotypes. The average and gestational age of subjects were 27.95 ± 5.78 years and 27.78 ± 3.57 weeks, respectively. The distribution of α-thalassemia, ß-thalassemia, and normal cases was 67.87%, 19.68%, and 12.45%, respectively. Significant differences in almost all the hematological parameters (HbF, HbA, Hb, HCT, MCV, MCH, MCHC, RDW, and NBRCs) were observed in three groups (P < 0.001, except for RBC, P = 0.446). These differences were also observed in four α-thalassemia subgroups (P < 0.001) and were associated with the number of defected genes. Similarly, in five ß-thalassemia genotypes, HbF, HbA, RBC, MCV, MCH and NBRCs were presented differently (P < 0.05). Additionally, the trends in RBC, Hb, and HCT changes in three α-thalassemia subgroups (silent carrier, trait, and major) and ß+/ß+ fetuses' MCV, MCH, and RDW levels with gestation age were opposite to those of normal fetuses. We compared the distribution of hematological parameters in fetuses affected by most genotypes of thalassemia, as well as their trends in relation to gestational age for the first time, which is a good reference for future studies and prenatal diagnostic practices. The investigated hematological parameters are also valuable in diagnosing and differentiating thalassemia.
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Biomarcadores/sangue , Índices de Eritrócitos , Sangue Fetal , Talassemia alfa/sangue , Talassemia alfa/epidemiologia , Talassemia beta/sangue , Talassemia beta/epidemiologia , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Genótipo , Idade Gestacional , Humanos , Mutação , Gravidez , Adulto Jovem , alfa-Globinas/genética , Talassemia alfa/genética , Globinas beta/genética , Talassemia beta/genéticaRESUMO
Hand, foot, and mouth disease (HFMD) is a common infectious disease affecting mainly children under 5 years of age. Coxsackievirus A6 (CVA-6), a major causative pathogen of HFMD, has caused outbreaks in recent years. Currently, no effective vaccine or antiviral treatments are available. In this study, one-step reverse-transcription recombinase polymerase amplification (RT-RPA), combined with a disposable lateral flow strip (LFS) assay, was developed to detect CVA-6. This assay can be performed in less than 35 min at 37°C without expensive instruments, and the result can be observed directly with the naked eye. The sensitivity of the RT-RPA-LFS was 10 copies per reaction, which was comparable to that of the conventional real-time quantitative polymerase chain reaction (qPCR) assays. Moreover, the assay specificity was 100%. The clinical performance of the RT-RPA-LFS assay was evaluated using 142 clinical samples, and the coincidence rate between RT-RPA-LFS and qPCR was 100%. Therefore, our RT-RPA-LFS assay provides a simple and rapid approach for point-of-care CVA-6 diagnosis.
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Objective: Although genetic variants of key enzymes in the folic acid-methionine metabolic circulation, including methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) were thought to be related to the risk of recurrent pregnancy loss (RPL), the results of recent studies have been inconsistent. Therefore, the present retrospective case-control study was designed to explore whether the variants c.66A>G in MTRR and c.677C>T and c.1298A>C in MTHFR are associated with the susceptibility of RPL in Southeast Chinese women. Materials and Methods: In total, samples from 237 RPL patients and 618 healthy controls were collected and genotyped by fluorescent quantitative polymerase chain reaction. The frequencies of the variants were calculated and compared between the two groups. The relative risk of the various genotypes was further determined by calculating the odds ratio (OR) at a 95% confidence interval (CI). Results: A significant positive correlation was observed between the variants MTHFR c.677C>T, MTHFR c.1298A>C, MTRR c.66A>G, and RPL susceptibility (MTHFR c.677C>T, OR = 0.74, 95% CI = 0.58-0.95, p = 0.02; MTHFR c.1298A>C, OR = 1.39, 95% CI = 1.09-1.77, p = 0.008; MTRR c.66A>G, OR = 1.38, 95% CI = 1.10-1.73, p = 0.006). Further analysis of the genotypic distributions of the three variants between the two groups showed that the MTHFR c.677C>T heterozygote was associated with lower RPL risk, while the MTHFR c.1298A>C variant and MTRR c.66A>G heterozygote were correlated with higher RPL risk (dominant model, MTHFR c.677C>T, OR = 0.70, 95% CI = 0.52-0.95, p = 0.02; MTHFR c.1298A>C, OR = 1.39, 95% CI = 1.03-1.88, p = 0.032; MTRR c.66A>G, OR = 1.62, 95% CI = 1.20-2.19, p = 0.002). Conclusion: MTHFR c.677C>T and c.1298A>C and MTRR c.66A>G were associated with RPL in Southeast Chinese women.
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Aborto Espontâneo/genética , Ferredoxina-NADP Redutase/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Aborto Habitual/genética , Aborto Espontâneo/metabolismo , Adolescente , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Gravidez , Estudos RetrospectivosRESUMO
ß-Globin gene mutations reduce or terminate the production of beta globin chains, of which approximately 10% are large deletions within the ß-globin gene cluster. Because gene deletion leads to loss of heterozygosity at single nucleotide polymorphism (SNP), a novel method for detecting ß-globin gene cluster deletions based on SNP heterozygosity analysis was established in this study. The location range of SNPs was selected according to the breakpoint of ß-globin gene cluster deletions. SNPs were screened using bioinformatics analysis and population sequencing data. A novel method which enables genotyping of multiplex SNPs based on tetra-primer ARMS-PCR was designed and optimized. Forty clinical samples were tested in parallel by this method and MLPA to verify the performance of this method for detecting ß-globin gene cluster deletion. Six informative SNPs were obtained, achieving heterozygote coverage of 93.3% in normal individuals. Genotyping of six SNPs were successfully integrated into two multiplex tetra-primer ARMS-PCR reactions. The sensitivity, specificity, positive predictive value and negative predictive value of the method for detecting ß-globin gene cluster deletion were 100%, 96.30%, 92.86%, and 100%, respectively. This is a simple, cost-effective and novel method for detecting ß-globin gene cluster deletions, which may be suitable for use in combination with MLPA for thalassemia molecular testing.
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Biologia Computacional/métodos , Técnicas de Genotipagem/métodos , Polimorfismo de Nucleotídeo Único , Globinas beta/genética , Deleção de Genes , Heterozigoto , Humanos , Família Multigênica , Reação em Cadeia da Polimerase Multiplex , Análise de Sequência de DNARESUMO
BACKGROUND: Coxsackievirus A6 (CA6) infection may lead to high hand-foot-and-mouth disease (HFMD) aggregation in children. We aimed to analyze the clinical and phylogenetic features of severe CA6-associated pediatric HFMD. METHODS: The clinical and laboratory features of 206 and 55 children with mild and severe CA6-associated HFMD, respectively, were summarized. The CA6 phylogenetic tree was depicted using combinatorial analysis of the VP1-encoding regions and neighbor-joining method. RESULTS: CA6 was the major pathogen both in mild and severe HFMD in 2017. Most CA6-associated severe HFMD cases showed high fever, skin rash, age younger than 36â¯months, and elevated white blood cell and C-reactive protein levels, and there were no significant differences compared to the mild cases (pâ¯>â¯0.05). The severe cases were significantly more likely (pâ¯<â¯0.05) to show male sex, long fever duration, decreased oral intake, tonsil enlargement, diarrhea, vomiting, elevated levels of creatine kinase and blood glucose, and positive fecal occult-blood test results. Severe complications included aseptic meningitis (29/55, 52.7%) and pulmonary edema (6/55, 10.9%) were observed in severe cases. Furthermore, genetic analyses showed all CA6 isolates belonged to lineage E2, and two amino acid changes of V174I and T283A in VP1 may be associated with the severity of HFMD. CONCLUSIONS: CA6 has become a major cause of HFMD with severe systemic disorders. V174I and T283A of VP1 may be associated with the severity of CA6 infection. These findings could raise awareness of the clinical importance of CA6 infection among practitioners.
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Proteína C-Reativa/metabolismo , Proteínas do Capsídeo/genética , Enterovirus Humano A/classificação , Doença de Mão, Pé e Boca/virologia , Substituição de Aminoácidos , Criança , Pré-Escolar , Enterovirus Humano A/genética , Enterovirus Humano A/isolamento & purificação , Feminino , Doença de Mão, Pé e Boca/sangue , Doença de Mão, Pé e Boca/metabolismo , Humanos , Lactente , Contagem de Leucócitos , Masculino , Filogenia , Índice de Gravidade de DoençaRESUMO
Conventional culture method for detecting Group B streptococcus (GBS), a common pathogen of neonatal meningitis and sepsis, is time-consuming and unsensitive. Even though real-time fluorescence PCR-based molecular method is more accurate, it need special instrument and elaborate protocol. Here, we established a novel molecular method combining recombinase polymerase amplification with lateral flow strips for detecting GBS. The cAMP factor (cfb) gene is a highly specific and sensitive biomarker to identify GBS and is detectable by using 100 genomic copies as the amplification template. Clinical performance of this assay was evaluated by testing 130 samples, in comparison with culture method and real-time fluorescence PCR, and the results achieved 100% accuracy, which were the same with those of real-time fluorescence PCR, and were better than those of culture method with false-negative detection. This study provides a rapid and visual method, with clinical potential, for the detection of GBS infection of patients.
Assuntos
Técnicas Bacteriológicas/métodos , Técnicas Biossensoriais/métodos , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/isolamento & purificação , Proteínas de Bactérias/genética , DNA Bacteriano/genética , Feminino , Proteínas Hemolisinas/genética , Humanos , Limite de Detecção , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Sistemas Automatizados de Assistência Junto ao Leito , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Streptococcus agalactiae/genéticaRESUMO
Although the SLE risk gene loci of HLA-DR and HLA-DQ within the major histocompatibility complex (MHC) region has been gradually revealed by recent Genome-Wide Association studies (GWAS), the association of HLA-DP polymorphisms with SLE was minimally reported. Considering that the variants in rs3077 and rs9277535 in the HLA-DP region could influence the immune response by affecting antigen presentation of HLA class II molecules to CD4+ T cells, the present study aimed to explore the role of HLA-DP polymorphisms in SLE. In total, samples from 335 SLE patients and 635 healthy controls were collected and genotyped by a polymerase chain reaction-high resolution melting (PCR-HRM) assay. A significant positive correlation was observed between the SNP rs3077, rs9277535 of HLA-DP and SLE susceptibility (rs3077, OR = 0.74, 95%CI = 0.60-0.91, P = 0.004; rs9277535, OR = 0.72, 95%CI = 0.59-0.88, P = 0.001). Rs3077 polymorphism was corelated to IL-17, INF-γ and cutaneous vasculitis (P = 0.037, P = 0.020 and P = 0.006, respectively). Additionally, rs3077 AA genotype carriers showed lower concentration of inflammatory cytokines and lower cutaneous vasculitis incidence than did the other two genotype. No significant association was observed between rs9277535 and cytokines or any clinical features. In conclusion, HLA-DP polymorphisms (rs3077 and rs9277535) were associated with SLE susceptibility and the levels of some inflammatory cytokines in SLE patients.