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Background Adequate safe margin in tongue cancer radical surgery is one of the most important prognostic factors. However, the role of peritumoral tissues in predicting lymph node metastasis (LNM) and prognosis using radiomics analysis remains unclear. Purpose To investigate whether magnetic resonance imaging (MRI)‐based radiomics analysis with peritumoral extensions contributes toward the prediction of LNM and prognosis in tongue cancer. Study type Retrospective. Population Two hundred and thirty‐six patients (38.56% female) with tongue cancer (training set, N = 157; testing set, N = 79; 37.58% and 40.51% female for each). Field Strength/Sequence 1.5 T; T2‐weighted turbo spin‐echo images. Assessment Radiomics models (Rprim, Rprim+3, Rprim+5, Rprim+10, Rprim+15) were developed with features extracted from the primary tumor without or with peritumoral extensions (3, 5, 10, and 15 mm, respectively). Clinicopathological characteristics selected from univariate analysis, including MRI‐reported LN status, radiological extrinsic lingual muscle invasion, and pathological depth of invasion (DOI) were further incorporated into radiomics models to develop combined radiomics models (CRprim, CRprim+3, CRprim+5, CRprim+10, CRprim+15). Finally, the model performance was validated in the testing set. DOI was measured from the adjacent normal mucosa to the deepest point of tumor invasion. Statistical Tests Chi‐square test, regression analysis, receiver operating characteristic curve (ROC) analysis, decision analysis, spearman correlation analysis. The Delong test was used to compare area under the ROC (AUC). P < 0.05 was considered statistically significant. Results Of all the models, the CRprim+10 reached the highest AUC of 0.995 in the training set and 0.872 in the testing set. Radiomics features were significantly correlated with pathological DOI (correlation coefficients, −0.157 to −0.336). The CRprim+10 was an independent indicator for poor disease‐free survival (hazard ratio, 5.250) and overall survival (hazard ratio, 17.464) in the testing set. Data Conclusion Radiomics analysis with a 10‐mm peritumoral extension had excellent power to predict LNM and prognosis in tongue cancer.

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A rapid and simple high-performance liquid chromatography-ultraviolet method was developed for the separation and quantification of 15 sulfonamides (SAs) in foods of animal origin without the need of clean-up procedure. A mixture of acetonitrile-formic acid-ammonium acetate-water was used as the mobile phase to separate 15 SAs on a C18 column with gradient. The selected SAs were separated completely from the matrix mixture based on different retention behaviors at different concentration of acetonitrile. The effects of the additive of formic acid and ammonium acetate in mobile phases on the separation of SAs were also investigated. The additive can greatly improve the resolution between SAs and impurities, so that the SAs can be quantified directly under the optimized chromatographic condition the sample preparation which does not need extra sample clean-up procedure. Complete baseline separation of 15 SAs was achieved in <40 min, the linear range is 0.01-130 μg/mL with a correlation coefficient R2-value > 0.999. Excellent method reproducibility was found by intra- and inter-day precisions with the relative standard deviation <9.5%. The detection limit was <11.0 ng/mL and it can be used for routine screening of the SA residues in foods of animal origin.

Fentanyl, a potent opioid analgesic that is used to treat cancer pain, is commonly administered with paclitaxel in advanced tumors. However, the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanism of action is not well studied. The purpose of this study was to investigate the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanisms of action. Pharmacokinetic parameters of paclitaxel were tested using reversed phase high-performance liquid chromatography (RP-HPLC). Aspartate transaminase (AST), alanine aminotransferase (ALT), and mouse liver histopathology were examined. Moreover, the cytotoxicity of anti-carcinogens was examined using 1-(4, 5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), and the intracellular accumulation of doxorubicin and rhodamine 123 was detected by flow cytometry. Furthermore, the expression of ABCB1 and the activity of ABCB1 ATPase and CYP3A4 were also examined. In this study, the co-administration of fentanyl and paclitaxel prolonged the half-life (t1/2) of paclitaxel from 1.455 hours to 2.344 hours and decreased the clearance (CL) from 10.997 ml/h to 7.014 ml/h in mice. Fentanyl significantly increased the levels of ALT in mice to 88.2 U/L, which is more than 2-fold higher than the level detected in the control group, and it increased the histological damage in mouse livers. Furthermore, fentanyl enhanced the cytotoxicity of anti-carcinogens that are ABCB1 substrates and increased the accumulation of doxorubicin and rhodamine 123. Additionally, fentanyl stimulated ABCB1 ATPase activity and inhibited CYP3A4 activity in the liver microsomes of mice. Our study indicates that the obvious hepatotoxicity during this co-administration was due to the inhibition of CYP3A4 activity and ABCB1 transport activity. These findings suggested that the accumulation-induced hepatotoxicity of paclitaxel when it is combined with fentanyl should be avoided.

A Tempol compound with an amine group (4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl, NH-Tempol) was cross-linked to hemoglobin in a one-step polymerization reaction to produce a novel hemoglobin-based oxygen carrier (HBOC) designated PolyHb-Tempol. The reaction parameters, including the reaction time, pH, temperature, and ratio of reactants, were optimized, and the physiochemical properties of the resulting product were characterized. PolyHb-Tempol didn't show any toxicity towards endothelial cells. Furthermore, from observations of cell morphology and viability, PolyHb-Tempol showed a significant ability to inhibit or eliminate oxidative stress induced by superoxide free radicals. These results suggest that PolyHb-Tempol may potentially be suitable as an HBOC.

Objectives Ceftazidime/avibactam is not active against MBL-producing bacteria. Combining ceftazidime/avibactam or avibactam with aztreonam can counter the resistance of MBL-producing Enterobacterales. The aim of this study was to evaluate whether the addition of avibactam could reduce or close the mutant selection window (MSW) of aztreonam in Escherichia coli and Klebsiella pneumoniae harbouring MBLs; MSW is a pharmacodynamic (PD) parameter for the selection of emergent resistant mutants. Methods In vitro susceptibility of 19 clinical isolates to ceftazidime/avibactam, aztreonam alone, and in co-administration (aztreonam/ceftazidime/avibactam and aztreonam/avibactam) was determined, as well as the mutant prevention concentration (MPC). The fraction of time within 24 h that the free drug concentration was within the MSW (fTMSW) and the fraction of time that the free drug concentration was above the MPC (fT&gt;MPC) in both plasma and epithelial lining fluid (ELF) were determined from simulations of 10 000 profiles. The joint PTA was used to derive a joint cumulative fraction of response (CFR). Results All isolates were resistant to ceftazidime/avibactam or aztreonam. Combining aztreonam and avibactam or ceftazidime/avibactam resulted in synergistic bactericidal activities against all isolates. Synergism was primarily due to the aztreonam/avibactam combination. For aztreonam/avibactam dosing regimens evaluated in clinical trials, fT&gt;MPC values were &gt;90% and &gt;80%, whereas fTMSW measures were &lt;10% and &lt;20% in plasma and ELF, respectively. The CFR was 100% for aztreonam/avibactam against the collection of clinical isolates. Conclusions Effective antimicrobial combination optimized the PD parameters measuring selection for emergent mutants by increasing fT&gt;MPC and reducing fTMSW.

Mg-Zn-Y-Nd-Zr alloy has been developed as a new type of biodegradable orthopaedic implant material by the authors' research group with its excellent mechanical properties and controllable degradation rate. In this study, the cytocompatibility of Mg-Zn-Y-Nd-Zr alloy was systematically evaluated through in vitro cell culture method. MTT assay was applied to evaluate the cytotoxicity of Mg-Zn-Y-Nd-Zr alloy and no toxic effect was observed on L929 and MC3T3-E1 cells followed the protocol of ISO 10993 standard. Considering the potential ion accumulation in the bony environment, this study further investigated the cytotoxic effect of accumulated metallic ions during the alloy degradation by extending the extract preparation time. When the extract preparation time was prolonged to 1440 h, the accumulated metallic ions leaded to severe cell apoptosis, of which the combined ion concentration was determined as 39.5-65.8 µM of Mg, 3.5-5.9 µM of Zn, 0.44-0.74 µM of Y, 0.3-0.52 µM of Nd and 0.11-0.18 µM of Zr for L929, and 65.8-92.2 µM of Mg, 5.9-8.3 µM of Zn, 0.74-1.04 µM of Y, 0.52-0.73 µM of Nd and 0.18-0.25 µM of Zr for MC3T3-E1 cells. Besides the cell viability assessment, high expression of ALP activity and calcified nodules implied that metal elements in Mg-Zn-Y-Nd-Zr alloys can promote the osteogenic differentiation. Hence, excellent cytocompatibility has equipped Mg-Zn-Y-Nd-Zr alloy as a promising candidate for orthopaedic implant application, which can remarkably guide the magnesium-based alloy design and provide scientific evidence for clinical practice in future.