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Background. Acute generalized exanthematous pustulosis (AGEP) is a rare and serious adverse reaction of terbinafine. Understanding AGEP and terbinafine is primarily based on case reports. The purpose is to explore the clinical characteristics of terbinafine-induced AGEP, and to provide reference for clinical diagnosis and treatment. Methods. Case reports and original studies of terbinafine-induced AGEP were retrieved by searching Chinese and English databases from January, 1991, to May 31, 2022. Results. The median age of the 32 patients (17 males and 15 females) was 55 years (range: 6–84). The median time to onset of AGEP is 8 days (range: 1–77) and is usually accompanied by fever (>38°C) and elevated neutrophil levels (>8000/mm3). Four patients (12.5%) had oral mucosal involvement, and 10 patients (31.3%) developed postpustular desquamation. The lesions were mainly distributed in the trunk (43.8%), the whole body (34.4%), and the extremities (53.1%). Skin biopsy revealed subcorneal pustules (65.6%), intraepidermal cavernous pustules (43.8%), necrotic keratinocytes (15.6%), spongy hyperplasia (25.0%), neutrophil exocytosis (34.4%), and papillary dermal edema (40.6%). AGEP resolved completely in all patients at a median time of 12 days (range: 2–90) after discontinuation of terbinafine and symptomatic therapy. Conclusion. Clinicians should be aware that terbinafine-induced AGEP is a rare cutaneous adverse reaction. AGEP usually occurs within 2 weeks after administration and has a good prognosis after discontinuation.

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease that is closely related to obesity and metabolic disorders. 5-methoxyflavone (5-MF) is a flavonoid with DNA polymerase-β inhibitory properties. In this study, we explored the effects of 5-MF on NAFLD and its potential mechanisms using oleic acid/palmitic acid-treated HepG2 cells and high-fat diet-fed C57BL/6J mice. Our results showed that 5-MF not only alleviated fat deposition and hepatic steatosis, but also improved oxidative damage. In addition, 5-MF has the effect of alleviating disorders of glucose metabolism and enhancing energy expenditure in HFD-induced obese mice. Mechanistically, reverse screening methods and molecular docking analysis were used in combination, and revealed that cytochrome P450 1A1 (CYP1A1) is the target for 5-MF. Further experiments showed that 5-MF ameliorated triglycerides deposition by inhibiting the enzyme activity and protein expression of CYP1A1. In conclusion, 5-MF provides a novel strategy for the prevention and treatment of high-fat-induced NAFLD.

Yuan-yuan Wu,1 Wen-Hui Liao,1 Zong-ling Niu,1 Si-Han Zhou,1 Tian-Tian Wu,1 Zhe Li,2 Qi-Hua Zhao,1 Jing-Yuan Xu,2 Ming-jin Xie1 1School of Chemical Science and Technology, Yunnan University, Kunming, People’s Republic of China; 2Department of Chemical Biology and Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Ming-jin Xie, Email mjxie@ynu.edu.cnBackground: Gallium (III) metal-organic complexes have been shown to have the ability to inhibit tumor growth, but the poor water solubility of many of the complexes precludes further application. The use of materials with high biocompatibility as drug delivery carriers for metal-organic complexes to enhance the bioavailability of the drug is a feasible approach.Methods: Here, we modified the ligands of gallium 8-hydroxyquinolinate complex with good clinical anticancer activity by replacing the 8-hydroxyquinoline ligands with 5-bromo-8-hydroxyquinoline (HBrQ), and the resulting Ga(III) + HBrQ complex had poor water solubility. Two biocompatible materials, bovine serum albumin (BSA) and graphene oxide (GO), were used to synthesize the corresponding Ga(III) + HBrQ complex nanoparticles (NPs) BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs in different ways to enhance the drug delivery of the metal complex.Results: Both of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs can maintain stable existence in different solution states. In vitro cytotoxicity test showed that two nanomedicines had excellent anti-proliferation effect on HCT116 cells, which shown higher level of intracellular ROS and apoptosis ratio than that of cisplatin and oxaliplatin. In addition, the superior emissive properties of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs allow their use for in vivo imaging showing highly effective therapy in HCT116 tumor-bearing mouse models.Conclusion: The use of biocompatible materials for the preparation of NPs against poorly biocompatible metal-organic complexes to construct drug delivery systems is a promising strategy that can further improve drug delivery and therapeutic efficacy.Graphical Abstract: Keywords: gallium complex, nanomedicine, anticancer, colorectal cells, drug delivery, in vivo imaging

Benefiting from excellent mechanical properties, large surface area, rich hydroxyl groups, good sustainability, etc., nanocellulose is highly promising for various applications. However, intense chemical treatment and long-term processing are usually required to fabricate nanocellulose. Herein, a new synthesis method of nanocellulose is developed by using ultraviolet light irradiation-assisted delignification and subsequent sonification. This method is more cost-effective, time-saving, and environmentally benign compared to most of previously reported synthesis methods of nanocellulose. The obtained nanocellulose contains a small amount of lignin, which is unfavorable for high-temperature stability and optimal transparency. However, a small amount of lignin is beneficial to mechanical properties and in-water stability. With this nanocellulose, flexible MnO

Mucin 4 (MUC4) overexpression promotes tumorigenesis and increases the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). To date, no study has reported the association between radiomics and MUC4 expression in PDAC. Thus, we aimed to explore the utility of radiomics based on multi-sequence magnetic resonance imaging (MRI) to predict the status of MUC4 expression in PDAC preoperatively.This retrospective study included 52 patients with PDAC who underwent MRI. The patients were divided into two groups based on MUC4 expression status. Two feature sets were extracted from the arterial and portal phases (PPs) of dynamic contrast-enhanced MRI (DCE-MRI). Univariate analysis, minimum redundancy maximum relevance (MRMR), and principal component analysis (PCA) were performed for the feature selection of each dataset, and features with a cumulative variance of 90% were selected to develop radiomics models. Clinical characteristics were gathered to develop a clinical model. The selected radiomics features and clinical characteristics were modeled by multivariable logistic regression. The combined model integrated radiomics features from different selected data sets and clinical characteristics. The classification metrics were applied to assess the discriminatory power of the models.There were 22 PDACs with a high expression of MUC4 and 30 PDACs with a low expression of MUC4. The area under the receiver operating characteristic (ROC) curve (AUC) values of the arterial phase (AP) model, the PP model, and the combined model were 0.732 (0.591-0.872), 0.709 (0.569-0.849), and 0.861 (0.760-0.961), respectively. The AUC of the clinical model was 0.666 (0.600-0.682). The combined model that was constructed outperformed the AP, the PP, and the clinical models (P0.05, although no statistical significance was observed in the combined modelRadiomics models based on multi-sequence MRI have the potential to predict MUC4 expression levels in PDAC.

Many factors were reported to be associated with diabetic retinopathy (DR); however, their contributions remained unclear. We aimed to evaluate the prognostic and diagnostic accuracy of logistic regression and three machine learning models based on various medical records.This was a cross-sectional study. We investigated the prevalence and associations of DR among 757 participants aged 40 years or older in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). We trained the models to predict if the participants had DR with 15 predictor variables. Area under the receiver operating characteristic (AUROC) and mean squared error (MSE) of each algorithm were compared in the external validation dataset using a replicate cohort from NHANES 2007-2008.Among the 757 participants, 53 (7.00%) subjects had DR, the mean (standard deviation, SD) age was 57.7 (13.04), and 78.0% were male (n = 42). Logistic regression revealed that female gender (OR = 4.130, 95% CI: 1.820-9.380; P 0.05), HbA1c (OR = 1.665, 95% CI: 1.197-2.317; P 0.05), serum creatine level (OR = 2.952, 95% CI: 1.274-6.851; P 0.05), and eGFR level (OR = 1.009, 95% CI: 1.000-1.014, P 0.05) increased the risk of DR. The average performance obtained from internal validation was similar in all models (AUROC ≥ 0.945), and k-nearest neighbors (KNN) had the highest value with an AUROC of 0.984. In external validation, they remained robust or with modest reductions in discrimination with AUROC still ≥ 0.902, and KNN also performed the best with an AUROC of 0.982. Both logistic regression and machine learning models had good performance in the clinical diagnosis of DR.This study highlights the utility of comparing traditional logistic regression to machine learning models. We found that logistic regression performed as well as optimized machine learning methods when classifying DR patients.