Background Avian influenza A H7N9 emerged in 2013, threatening public health and causing acute respiratory distress syndrome, and even death, in the human population. However, the underlying mechanism by which H7N9 virus causes human infection remains elusive. Methods Herein, we infected A549 cells with H7N9 virus for different times and assessed tripartite motif-containing protein 46 (TRIM46) expression. To determine the role of TRIM46 in H7N9 infection, we applied lentivirus-based TRIM46 short hairpin RNA sequences and overexpression plasmids to explore virus replication, and changes in type I interferons and interferon regulatory factor 3 (IRF3) phosphorylation levels in response to silencing and overexpression of TRIM46. Finally, we used Co-immunoprecipitation and ubiquitination assays to examine the mechanism by which TRIM46 mediated the activity of TANK-binding kinase 1 (TBK1). Results Type I interferons play an important role in defending virus infection. Here, we found that TRIM46 levels were significantly increased during H7N9 virus infection. Furthermore, TRIM46 knockdown inhibited H7N9 virus replication compared to that in the control group, while the production of type I interferons increased. Meanwhile, overexpression of TRIM46 promoted H7N9 virus replication and decrease the production of type I interferons. In addition, the level of phosphorylated IRF3, an important interferon regulatory factor, was increased in TRIM46-silenced cells, but decreased in TRIM46 overexpressing cells. Mechanistically, we observed that TRIM46 could interact with TBK1 to induce its K48-linked ubiquitination, which promoted H7N9 virus infection. Conclusion Our results suggest that TRIM46 negatively regulates the human innate immune response against H7N9 virus infection.
Background Although the elderly constitute more than a third of hepatocellular carcinoma (HCC) patients, they have not been adequately represented in treatment and prognosis studies. Thus, there is not enough evidence to guide the treatment of such patients. The objective of this study is to identify the prognostic factors of older patients with HCC and to construct a new prognostic model for predicting their overall survival (OS). Methods 2,721 HCC patients aged ≥ 65 were extracted from the public database-Surveillance, Epidemiology, and End Results (SEER) and randomly divided into a training set and an internal validation set with a ratio of 7:3. 101 patients diagnosed from 2008 to 2017 in the First Affiliated Hospital of Zhejiang University School of Medicine were identified as the external validation set. Univariate cox regression analyses and multivariate cox regression analyses were adopted to identify these independent prognostic factors. A predictive nomogram-based risk stratification model was proposed and evaluated using area under the receiver operating characteristic curve (AUC), calibration curves, and a decision curve analysis (DCA). Results These attributes including age, sex, marital status, T stage, N stage, surgery, chemotherapy, tumor size, alpha-fetoprotein level, fibrosis score, bone metastasis, lung metastasis, and grade were the independent prognostic factors for older patients with HCC while predicting survival duration. We found that the nomogram provided a good assessment of OS at 1, 3, and 5 years in older patients with HCC (1-year OS: (training set: AUC = 0.823 (95%CI 0.803–0.845); internal validation set: AUC = 0.847 (95%CI 0.818–0.876); external validation set: AUC = 0.732 (95%CI 0.521–0.943)); 3-year OS: (training set: AUC = 0.813 (95%CI 0.790–0.837); internal validation set: AUC = 0.844 (95%CI 0.812–0.876); external validation set: AUC = 0.780 (95%CI 0.674–0.887)); 5-year OS: (training set: AUC = 0.839 (95%CI 0.806–0.872); internal validation set: AUC = 0.800 (95%CI 0.751–0.849); external validation set: AUC = 0.821 (95%CI 0.727–0.914)). The calibration curves showed that the nomogram was with strong calibration. The DCA indicated that the nomogram can be used as an effective tool in clinical practice. The risk stratification of all subgroups was statistically significant (p < 0.05). In the stratification analysis of surgery, larger resection (LR) achieved a better survival curve than local destruction (LD), but a worse one than segmental resection (SR) and liver transplantation (LT) (p < 0.0001). With the consideration of the friendship to clinicians, we further developed an online interface (OHCCPredictor) for such a predictive function (https://juntaotan.shinyapps.io/dynnomapp_hcc/). With such an easily obtained online tool, clinicians will be provided helpful assistance in formulating personalized therapy to assess the prognosis of older patients with HCC. Conclusions Age, sex, marital status, T stage, N stage, surgery, chemotherapy, tumor size, AFP level, fibrosis score, bone metastasis, lung metastasis, and grade were independent prognostic factors for elderly patients with HCC. The constructed nomogram model based on the above factors could accurately predict the prognosis of such patients. Besides, the developed online web interface of the predictive model provide easily obtained access for clinicians.
Background Length of stay (LOS) is an important metric for evaluating the management of inpatients. This study aimed to explore the factors impacting the LOS of inpatients with type-2 diabetes mellitus (T2DM) and develop a predictive model for the early identification of inpatients with prolonged LOS. Methods A 13-year multicenter retrospective study was conducted on 83,776 patients with T2DM to develop and validate a clinical predictive tool for prolonged LOS. Least absolute shrinkage and selection operator regression model and multivariable logistic regression analysis were adopted to build the risk model for prolonged LOS, and a nomogram was taken to visualize the model. Furthermore, receiver operating characteristic curves, calibration curves, and decision curve analysis and clinical impact curves were used to respectively validate the discrimination, calibration, and clinical applicability of the model. Results The result showed that age, cerebral infarction, antihypertensive drug use, antiplatelet and anticoagulant use, past surgical history, past medical history, smoking, drinking, and neutrophil percentage-to-albumin ratio were closely related to the prolonged LOS. Area under the curve values of the nomogram in the training, internal validation, external validation set 1, and external validation set 2 were 0.803 (95% CI [confidence interval] 0.799–0.808), 0.794 (95% CI 0.788–0.800), 0.754 (95% CI 0.739–0.770), and 0.743 (95% CI 0.722–0.763), respectively. The calibration curves indicated that the nomogram had a strong calibration. Besides, decision curve analysis, and clinical impact curves exhibited that the nomogram had favorable clinical practical value. Besides, an online interface (https://cytjt007.shinyapps.io/prolonged_los/) was developed to provide convenient access for users. Conclusion In sum, the proposed model could predict the possible prolonged LOS of inpatients with T2DM and help the clinicians to improve efficiency in bed management.
A large number of papers have been published since the discovery of the monkeypox virus (MPXV). In 2022, human MPXV broke out in the USA and many European countries, and on July 23 of that year, the World Health Organization declared the MPXV outbreak a "Public Health Emergency of International Concern." In this study, we performed bibliometric analysis of MPXV literature published in core journals of the Web of Science core Collection database, which was conducted on 956 articles from 2000 to 2022. We analyzed the publication country, subject category, main authors and institutions, research hotspots of important publications and research frontiers. Through the analysis of keywords co-occurrence, multi-cited literature and co-cited literature, the research hotspots and trends were summarized. This report revealed that MPXV research has focused on hot areas such as infection and vaccination. Since the 2022 human MPXV outbreak, researchers have increasingly focused on infection control, vaccines, and treatment of monkeypox. This article summarizes the research directions and hotspots of MPXV related literature since the 2000, and we hope to provide support and clear research ideas for the future research and prevention of MPXV in humans.
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