Association of ABCC2 and CDDP-Resistance in Two Sublines Resistant to CDDP Derived from a Human Nasopharyngeal Carcinoma Cell Line

Cisplatin (CDDP) is one of the most active drugs to treat nasopharyngeal carcinoma (NPC) patients. To further understand the mechanisms of CDDP-resistance in NPC, two CDDP-resistant sublines (CNE2-CDDP and CNE2-CDDP-5Fu) derived from parental NPC cell line CNE2 were established. It was found that at the IC50 level, the resistance of CNE2-CDDP and CNE2-CDDP-5Fu against CDDP was 2.63-fold and 5.35-fold stronger than that of parental CNE2, respectively. Of the four ABC transporters (ABCB1, ABCC1, ABCC2 and ABCG2) related to MDR, only ABCC2 was found to be elevated both in CDDP-resistant sublines, with ABCC2 located in nucleus of CNE2-CDDP-5Fu but not in CNE2-CDDP and parental CNE2. Further research showed that compared to untreated CNE2, the intracellular levels of CDDP were decreased by 2.03-fold in CNE2-CDDP and 2.78-fold in CNE2-CDDP-5Fu. After treatment with PSC833, a modulator of MDR associated transporters including ABCC2, the intracellular level of CDDP was increased in CDDP-resistant sublines, and the resistance to CDDP was partially reversed from 2.63-fold to 1.62-fold in CNE2-CDDP and from 5.35-fold to 4.62-fold in CNE2-CDDP-5Fu. These data indicate that ABCC2 may play an important role in NPC resistant to CDDP

Prevalence and spectrum of Nkx2.5 mutations associated with idiopathic atrial fibrillation

OBJECTIVE: The aim of this study was to evaluate the prevalence and spectrum of Nkx2.5 mutations associated with idiopathic atrial fibrillation (AF). METHODS: A cohort of 136 unrelated patients with idiopathic atrial fibrillation and 200 unrelated, ethnically matched healthy controls were enrolled. The coding exons and splice junctions of the Nkx2.5 gene were sequenced in 136 atrial fibrillation patients, and the available relatives of mutation carriers and 200 controls were subsequently genotyped for the identified mutations. The functional characteristics of the mutated Nkx2.5 gene were analyzed using a dual-luciferase reporter assay system. RESULTS: Two novel heterozygous Nkx2.5 mutations (p.N19D and p.F186S) were identified in 2 of the 136 unrelated atrial fibrillation cases, with a mutational prevalence of approximately 1.47%. These missense mutations co-segregated with atrial fibrillation in the families and were absent in the 400 control chromosomes. Notably, 2 mutation carriers also had congenital atrial septal defects and atrioventricular block. Multiple alignments of the Nkx2.5 protein sequences across various species revealed that the altered amino acids were completely conserved evolutionarily. Functional analysis demonstrated that the mutant Nkx2.5 proteins were associated with significantly reduced transcriptional activity compared to their wild-type counterpart. CONCLUSION: These findings associate the Nkx2.5 loss-of-function mutation with atrial fibrillation and atrioventricular block and provide novel insights into the molecular mechanism involved in the pathogenesis of atrial fibrillation. These results also have potential implications for early prophylaxis and allele-specific therapy of this common arrhythmia

Automatic Visual Inspection and Condition-Based Maintenance for Catenary

Defects on catenary components are a major part of device faults as a result of a much higher tension on high-speed catenary, such as looseness of bolts, component broken, and component missing. Traditional inspection on catenary components has to be performed only at night with human eyes. Not only the inspection speed is very slow but also the inspection results are not reliable, as a result of the poor lighting environment and long-time working tiredness. In this chapter, we present an automatic visual inspection system for checking the status of components on catenary. A dedicated designed camera system is mounted on an inspection car, which covers almost all the components to be checked and gives great details of each component. Considering the great data storm at each catenary post, high-performance servers with GPU acceleration are used, and technologies of multi-thread and parallel computing are exploited. Furthermore, an intelligent analysis framework is proposed, which uses structural analysis to localize each component in the image and perform automatic detection based on different features such as geometry, texture, and logic rules. The system has been successfully used in China’s high-speed railways, which shows great advantages in the catenary inspection application

Nighttime Thermal Infrared Image Colorization with Feedback-based Object Appearance Learning

Stable imaging in adverse environments (e.g., total darkness) makes thermal infrared (TIR) cameras a prevalent option for night scene perception. However, the low contrast and lack of chromaticity of TIR images are detrimental to human interpretation and subsequent deployment of RGB-based vision algorithms. Therefore, it makes sense to colorize the nighttime TIR images by translating them into the corresponding daytime color images (NTIR2DC). Despite the impressive progress made in the NTIR2DC task, how to improve the translation performance of small object classes is under-explored. To address this problem, we propose a generative adversarial network incorporating feedback-based object appearance learning (FoalGAN). Specifically, an occlusion-aware mixup module and corresponding appearance consistency loss are proposed to reduce the context dependence of object translation. As a representative example of small objects in nighttime street scenes, we illustrate how to enhance the realism of traffic light by designing a traffic light appearance loss. To further improve the appearance learning of small objects, we devise a dual feedback learning strategy to selectively adjust the learning frequency of different samples. In addition, we provide pixel-level annotation for a subset of the Brno dataset, which can facilitate the research of NTIR image understanding under multiple weather conditions. Extensive experiments illustrate that the proposed FoalGAN is not only effective for appearance learning of small objects, but also outperforms other image translation methods in terms of semantic preservation and edge consistency for the NTIR2DC task.Comment: 14 pages, 14 figures. arXiv admin note: text overlap with arXiv:2208.0296

Home enteral nutrition for patients with esophageal cancer undergoing esophagectomy: A systematic review and meta-analysis

IntroductionHome enteral nutrition (HEN) is a relatively new nutritional intervention that provides patients with EN support at home through jejunostomy or nasogastric feeding tubes. We conducted this systematic review and meta-analysis to explore the safety and effect of HEN compared with normal oral diet (NOD) in postoperative patients with esophageal cancer (EC).MethodsEMBASE, Medline, Web of Science, and the Cochrane Library were used to search articles in English-language journals. The intervention effect was expressed using risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcome measures, with 95% confidence intervals (95% CIs). The chi-square test and I-square test were used to test heterogeneity among studies.ResultsFour studies were eventually included in this meta-analysis. Compared with NOD, HEN has a favorable impact on postoperative body mass index (BMI) (weighted mean difference [WMD] = 0.70, 95% CI: 0.09–1.30, P = 0.02), lean body mass (LBM) (WMD = 0.76, 95% CI: 0.04–1.48, P = 0.04), and appendicular skeletal muscle mass index (ASMI) (WMD = 0.30, 95% CI: 0.02–0.58, P = 0.03). Physical function (WMD = 9.26, 95% CI: 8.00–10.53, P < 0.001), role function (WMD = 9.96, 95% CI: 8.11–11.82, P < 0.001), and social function (WMD = 8.51, 95% CI: 3.48–13.54, P = 0.001) of the HEN group were better than those of the NOD group at 3 months, and HEN could reduce the fatigue of patients (WMD = −12.73, 95% CI: −14.8 to −10.66, P < 0.001) and the incidence of postoperative pneumonia (RR = 0.53, 95% CI: 0.34–0.81, P = 0.004). There was no significant difference in albumin between HEN and NOD groups (WMD = 0.05, 95% CI: −0.03 to 0.13, P = 0.20).ConclusionHEN improved nutritional status and quality of life (QOL) in postoperative patients with EC and reduced fatigue and the incidence of postoperative pneumonia. All in all, the results of our meta-analysis support the use of HEN after esophagectomy

A new model based on gamma-glutamyl transpeptidase to lymphocyte ratio and systemic immune-inflammation index can effectively predict the recurrence of hepatocellular carcinoma after liver transplantation

BackgroundLiver transplantation (LT) is one of the most effective treatment modalities for hepatocellular carcinoma (HCC), but patients with HCC recurrence after LT always have poor prognosis. This study aimed to evaluate the predictive value of the gamma-glutamyl transpeptidase-to-lymphocyte ratio (GLR) and systemic immune-inflammation index (SII) in terms of HCC recurrence after LT, based on which we developed a more effective predictive model.MethodsThe clinical data of 325 HCC patients who had undergone LT were collected and analyzed retrospectively. The patients were randomly divided into a development cohort (n = 215) and a validation cohort (n = 110). Cox regression analysis was used to screen the independent risk factors affecting postoperative recurrence in the development cohort, and a predictive model was established based on the results of the multivariate analysis. The predictive values of GLR, SII and the model were evaluated by receiver operating characteristic (ROC) curve analysis, which determined the cut-off value for indicating patients’ risk levels. The Kaplan-Meier survival analysis and the competing-risk regression analysis were used to evaluate the predictive performance of the model, and the effectiveness of the model was verified further in the validation cohort.ResultsThe recurrence-free survival of HCC patients after LT with high GLR and SII was significantly worse than that of patients with low GLR and SII (P<0.001). Multivariate Cox regression analysis identified GLR (HR:3.405; 95%CI:1.954-5.936; P<0.001), SII (HR: 2.285; 95%CI: 1.304-4.003; P=0.004), tumor number (HR:2.368; 95%CI:1.305-4.298; P=0.005), maximum tumor diameter (HR:1.906; 95%CI:1.121-3.242; P=0.017), alpha-fetoprotein level (HR:2.492; 95%CI:1.418-4.380; P=0.002) as independent risk factors for HCC recurrence after LT. The predictive model based on these risk factors had a good predictive performance in both the development and validation cohorts (area under the ROC curve=0.800, 0.791, respectively), and the performance of the new model was significantly better than that of single GLR and SII calculations (P<0.001). Survival analysis and competing-risk regression analysis showed that the predictive model could distinguish patients with varying levels of recurrence risk in both the development and validation cohorts.ConclusionsThe GLR and SII are effective indicators for evaluating HCC recurrence after LT. The predictive model based on these indicators can accurately predict HCC recurrence after LT and is expected to guide preoperative patient selection and postoperative follow-up