RESUMEN
BACKGROUND: Compared with methicillin sensitive Staphylococcus aureus (MSSA), the prognosis of patients with methicillin resistant Staphylococcus aureus (MRSA) bloodstream infection is poor. Therefore, the construction of MRSA and MSSA identification model has certain value for the selection of antibiotics and treatment outcome control. This study aimed to derive and validate a simple risk prediction model for MRSA bloodstream infection in Chinese patients. METHODS: Three hundred and thirty-five patients with Staphylococcus aureus (S. aureus) bloodstream infection were retrospectively analyzed and divided into three groups. The first group was used for the risk score derivation (n = 163), the second group was used for internal validation (n = 80), and the third group was used for external validation (n = 92). According to the odds ratio (OR) obtained from multivariate logistic regression, the risk prediction model for MRSA bloodstream infection was established, and the prediction efficiency of the model in three cohorts were evaluated. RESULTS: Hospital stay before BSI ≥ 7 days, hospital acquired BSI, infection source ≥ 2 sites, indwelling gastric tube before BSI and carbapenems used before BSI and after admission were independent influencing factors of MRSA in the derivation group, the above influencing factors were scored 3, 5, 4, 3, and 3, respectively. The derivation, internal and external validation groups showed adequate discrimination (the AUCs were 0.788, 0.780, and 0.742, respectively) and good calibration (H-L tests were χ2 = 3.896, p = 0.306; χ2 = 4.221, p = 0.298; and χ2 = 3.974, p = 0.352, respectively). The risk scores were further divided into very low-risk (score 0 - 3), low-risk (score 4 - 7), high-risk (score 8 - 12), and very high-risk (score ≥ 13) layers. CONCLUSIONS: The simple risk score model for predicting MRSA bloodstream infection has good predictive effect, high predictive accuracy, and good clinical applicability, which can help clinicians choose sensitive antibiotics and reduce the adverse prognosis of patients.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Sepsis , Infecciones Estafilocócicas , Humanos , Staphylococcus aureus , Estudios Retrospectivos , Factores de Riesgo , Antibacterianos/uso terapéutico , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
OBJECTIVE: To investigate the molecular mechanism of hsa_circ_0005221 regulating the progression of PCa through the miR-339-5p/STAT5a pathway. METHODS: Localizations of hsa_circ_0005221 and miR-339-5p in cells were detected by nuclear-cytoplasmic isolation. MiRNA-339-5p was selected as the target miRNA bound to hsa_circ_0005221 by RNA pull-down assay. The binding site of the luciferase reporter gene was predicted by software and the binding capability of miR-339-5p validated by luciferase assay. The expression of hsa_circ_0005221 in the prostatic epithelial and PCa cells was determined by qPCR. The hsa_circ_0005221-overexpressed plasmid and siRNA were transfected into the PCa cells for measurement of their proliferation, invasion and migration abilities and the levels of epithelial-mesenchymal transformation (EMT) and apoptosis. After knockdown of hsa_circ_0005221 and transfection of miR-339-5p mimics and miR-339-5p inhibitor, the proliferation, invasion and migration abilities of the DU145 and LNCaP cells were detected, and so were the levels of the EMT signature protein, STAT5a and cell apoptosis. RESULTS: The expression of hsa_circ_0005221 was significantly higher in the PCa than in the prostatic epithelial cells. Nuclear-cytoplasmic isolation experiments showed that hsa_circ_0005221 and miR-339-5p were mainly located in the cytoplasm. The proliferation, invasion and migration abilities and EMT were decreased and the apoptosis increased in the DU145 and LNCaP cells with knockdown of hsa_circ_0005221, which was just the reverse in those with overexpressed hsa_circ_0005221. Among the top 5 miRNAs predicted by software, miR-339-5p, miR-17 and miR-520h were shown by pull-down assay to be bound to hsa_circ_0005221, with most obvious changes in miR-339-5p when hsa_circ_0005221 knocked down or overexpressed. Luciferase reporter gene assay showed the binding of hsa_circ_0005221 to miR-339-5p. Knockdown of hsa_circ_0005221 and transfection of miR-339-5p mimics into the DU145 and LNCaP cells significantly reduced the proliferation, invasion and migration abilities of the cells and the N-cad level, increased their apoptosis and E-cad level, and up-regulated the expression of STAT5a, while overexpression of hsa_circ_0005221 and transfection of miR-339-5p mimics induced just the opposite effects. CONCLUSIONS: Hsa_circ_0005221 enhances the progression of prostate cancer through the miR-339-5p/STAT5a pathway.
Asunto(s)
MicroARNs , Neoplasias de la Próstata , ARN Circular/genética , Factor de Transcripción STAT5 , Humanos , Masculino , MicroARNs/genética , Pelvis , Próstata , Neoplasias de la Próstata/genética , ARN Interferente Pequeño , Factor de Transcripción STAT5/genética , Proteínas Supresoras de TumorRESUMEN
OBJECTIVE: The diagnosis of relapsing polychondritis (RP) is often mistaken or delayed. In this retrospective cohort, we aimed to unveil the causes responsible for such phenomenon, to determine the associated factors, and to compare diagnosis in clinical settings with the current diagnostic criteria. METHOD: Eighty-seven RP patients followed-up by rheumatologists from January 1, 2008, to October 31, 2018, were retrospectively analyzed. RESULTS: A total of 50 male and 37 female patients were included with a mean age of 45.9 ± 14.5 years. Ninety-three percent were initially admitted by non-rheumatologic specialists .Twenty-eight percent were correctly diagnosed, while 72% were misdiagnosed at the first visits, all by non-rheumatologic specialists. Patients admitted by non-rheumatologic specialists had increased odds of misdiagnosis (odds ratio [OR] = 1.3, 95% confidence interval [95% CI] 1.1-1.7, P = 0.000). Fifty-seven (65.5%) patients did not meet with Michet or Damiani criteria, with 16 (18.4%) patients diagnosed as partial RP and 41( 47.1%) patients diagnosed as limited RP. CONCLUSIONS: Incorrect and delayed diagnosis of RP is common in our cohort, and insufficient awareness of the disease in non-rheumatologic specialists at least partially contributes to this. It is imperative to revise the current criteria for early diagnosis.Key Points⢠Diagnosing relapsing polychondritis (RP) in early stage remains challenging after all these years, especially among non-rheumatologic specialists, indicating the importance of teaching non-rheumatologic specialists to improve their understanding of this rare disease.⢠Many RP patients did not fully meet with the current criteria, suggesting that revision of the current criteria is imperative for early diagnosis of this rare disease.