The aim of this study was to investigate the molecular characteristics and in vitro susceptibility to bedaquiline of Mycobacterium tuberculosis (MTB) isolates from Shaanxi, China. Methods: The minimum inhibitory concentration (MIC) of bedaquiline was determined using the microplate alamarBlue assay for 518 MTB isolates from Shaanxi. Isolates with MIC values of bedaquiline !0.12 mg/mL were sequenced for the atpE, Rv0678, and pepQ genes. Drug susceptibility testing and spoligotyping were also conducted for all strains. Results: Ten (1.93%) bedaquiline-resistant strains were isolated from 518 tuberculosis patients. The resistance rate of bedaquiline was not correlated to sex, age, treatment history, region, or genotype. Five bedaquiline-resistant isolates and one bedaquiline-susceptible isolate were found to carry Rv0678 mutations; six mutation types were identified, including G5T, A263G, C185T, G19deletion, C265T, and T323C. No mutations within the atpE and pepQ genes were observed. Conclusions: Bedaquiline showed strong in vitro antibacterial activity against MTB isolates, and the Rv0678 gene serves as the major mechanism contributing to bedaquiline resistance among MTB isolates from Shaanxi, China. Two novel mutation types (C265 T and T323 C) of the Rv0678 gene were associated with resistance to bedaquiline. Furthermore, in addition to the current three resistance-associated genes (atpE, Rv0678, and pepQ), other mechanisms of resistance to bedaquiline may exist that need further study.
Background and AimsPrediction of pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) for breast cancer is critical for surgical planning and evaluation of NAC efficacy. The purpose of this project was to assess the efficiency of a novel nomogram based on ultrasound and clinicopathological features for predicting pCR after NAC.MethodsThis retrospective study included 282 patients with advanced breast cancer treated with NAC from two centers. Patients received breast ultrasound before NAC and after two cycles of NAC; and the ultrasound, clinicopathological features and feature changes after two cycles of NAC were recorded. A multivariate logistic regression model was combined with bootstrapping screened for informative features associated with pCR. Then, we constructed two nomograms: an initial-baseline nomogram and a two-cycle response nomogram. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were analyzed. The C-index was used to evaluate predictive accuracy.ResultsSixty (60/282, 21.28%) patients achieved pCR. Triple-negative breast cancer (TNBC) and HER2-amplified types were more likely to obtain pCR. Size shrinkage, posterior acoustic pattern, and elasticity score were identified as independent factors by multivariate logistic regression. In the validation cohort, the two-cycle response nomogram showed better discrimination than the initial-baseline nomogram, with the C-index reaching 0.79. The sensitivity, specificity, and NPV of the two-cycle response nomogram were 0.77, 0.77, and 0.92, respectively.ConclusionThe two-cycle response nomogram exhibited satisfactory efficiency, which means that the nomogram was a reliable method to predict pCR after NAC. Size shrinkage after two cycles of NAC was an important in dependent factor in predicting pCR.
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