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Objective: Hepatocellular carcinoma (HCC) has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence. This study aims to investigate the efficacy and safety of anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence factors., Methods: For this multicenter, retrospective study, we recruited 63 HCC patients who received either anlotinib (n=27) or transcatheter arterial chemoembolization (TACE) (n=36) from six research centers in China between March 2019 and October 2020. The primary endpoint was disease-free survival (DFS) and the secondary endpoints were overall survival (OS) and safety., Results: In this study, the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups, respectively. There was no significant difference in the median DFS between the anlotinib [26.8 months, 95% confidence interval (95% CI): 6.8-NE] and TACE groups (20.6 months, 95% CI: 8.4-NE). The 12-month OS rates in the anlotinib and TACE groups were 96.3% and 97.2%, respectively. In the anlotinib group, 19 of 27 patients (70.4%) experienced treatment-emergent adverse events, with the most common events (≥10%) being hypertension (22.2%) and decreased platelet count (22.2%)., Conclusions: The results indicate that anlotinib, as a new, orally administered tyrosine kinase inhibitor, has the same efficacy as TACE, and side effects can be well controlled., (Copyright ©2023 Chinese Journal of Cancer Research. All rights reserved.)

Fine particulate matter (PM 2.5 ) has been listed as an important environmental risk factor for human health. However, the systemic biological effects on metabolic responses induced by PM 2.5 and its components were poorly understood. This study was aimed to evaluate the toxicity of different components of PM 2.5 at molecular level via metabolomics approach. In the present study, we adopted a 1 H NMR-based metabolomics approach to evaluate metabolic profiles in mice after acute exposure to Total-PM 2.5 , water soluble components of PM 2.5 (WS-PM 2.5 ) and water insoluble components of PM 2.5 (WIS-PM 2.5 ). First, we characterized the morphological features and chemical composition of PM 2.5 . Then, the metabolites changes of serum and urine in mice were systematically analyzed using 800 MHz 1 H NMR techniques in combination with multivariate statistical analysis. Total-PM 2.5 exposure affected metabolites mainly involved in amino acid metabolism, protein biosynthesis, energy metabolism and metabolism of cofactors and vitamins. WS-PM 2.5 exposure influenced lipid metabolism and carbohydrate metabolism. WIS-PM 2.5 exposure mainly perturbed amino acid metabolism and energy metabolism. The results suggested that acute exposure to the Total-PM 2.5 , WS-PM 2.5 and WIS-PM 2.5 in mice exhibited marked systemic metabolic changes. In addition, the insoluble fraction of PM 2.5 contributed greatly to the toxicity of PM 2.5., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The reproductive toxicity of silica nanoparticles (SiNPs) is well known, but the underlying mechanism is still not clear. To investigate the toxic mechanism of SiNPs on spermatogenic cells, 60 C57 male mice were randomly and equally divided into three groups (the control group, the saline control group, and the SiNPs group) with two observed time points (45 days and 75 days). The mice in the SiNPs group were administered with SiNPs 2 mg/kg diluted in normal saline, and the mice of the saline control group were given equivoluminal normal saline by tracheal perfusion every 3 days for 45 days (in total 15 times). The control group mice were bred without treatment. In each group, a half number of the mice were sacrificed on the 45th day after the first dose, and the remaining half were sacrificed on the 75th day. The results showed that SiNPs increased the malformation of sperms and decreased the motility and concentration of sperms in epididymis on the 45th day after the first dose. SiNPs induced oxidative stress in testis and led to apoptosis and necroptosis of the spermatogenic cells. Furthermore, SiNPs increased the expression of Fas/FasL/RIPK1/FADD/caspase-8/caspase-3 and RIPK3/MLKL on the 45th day after the first dose. However, compared with the saline control group, the index of sperms and the expression of Fas/FasL/RIPK1/FADD/caspase-8/caspase-3/RIPK3/MLKL showed no significant changes in the SiNPs group on the 75th day after the first dose. These data suggested that SiNPs could induce apoptosis and necroptosis in the spermatogenic cells by activating the RIPK1 pathway resulting from oxidative stress in male mice. SiNPs-induced damage recovered on the 75th day after the first dose, which suggested that SiNPs-induced toxicity is reversible.

A solid-phase extraction (SPE) method for the simultaneous extraction of hexabromocyclododecanes (HBCDs)/tetrabromobisphenol A (TBBPA) and polybrominated diphenyl ethers (PBDEs) in human serum was developed. The extracts of HBCDs/TBBPA and PBDEs were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-negative chemical ionization/mass spectrometry (GC-NCI/MS), respectively. The samples with the spiked internal standards, 13C(12)-HBCD, 13C(12)-TBBPA, 3, 3', 4, 4'-tetrabromodiphenyl ether (BDE-77) and 13C(12)-decabromodiphenyl ether (BDE-209), were extracted using the mixture of methyl tert-butyl ether (MTBE) and hexane (1:1, v/v). Then the co-extracted lipid was removed by sulfuric acid treatment. The newly obtained extract was purified using SPE with an LC-Si column and two fractions of HBCDs/TBBPA and PBDEs were finally got. The determination of HBCDs/TBBPA was performed on a 50 mm BEH C18 column in the multi-reaction monitoring (MRM) mode and the determination of PBDEs was on a 15 m capillary column in the selected ion-monitoring (SIM) mode. The limits of detection (LODs, S/N = 3) ranged from 1.81 to 42.16 pg/g. The average recoveries were from 80.3% to 108.8% at two spiked levels of 0.5 and 5 ng/g for HBCDs, 0.05 and 0.5 ng/g for TBBPA and BDE-209 with the relative standard deviations between 1.02% and 11.42% (n = 5). The developed method has been successfully applied to the determination of the 12 analytes in 42 pooled human serum samples. The levels of TBBPA in the samples ranged from < LOD to 6.58 ng/g, that of alpha-HBCD diastereoisomer ranged from < LOD to 7.22 ng/g, which was the most abundant isomer comparing with beta- and gamma-HBCD. The total PBDEs found ranged from 2.90 to 89.69 ng/g. This method was validated to be accurate and sensitive for the analysis of HBCDs, TBBPA and PBDEs in serum samples.

Polybrominated diphenyl ethers (PBDEs) and dechlorane plus (DP) are two kinds of widely used organic flame retardants, and PBDE and DP residues have been found in both environment and biota. A method for the determination of 8 PBDEs and 2 DPs in fish and fish oil supplements was developed using auto gel permeation chromatography (GPC) coupled with gas chromatography-negative chemical ionization/mass spectrometry (GC-NCI/MS) in the selected ion-monitoring (SIM) mode on a 15 m capillary column. The sample added with BDE-77 and 13C12-BDE-209 as the internal standards was extracted using a Soxhlet extractor, and further purified by auto GPC and a multilayer silica gel column. The sample preparation procedure was optimized, and the characteristic ions and fragmentations of the analytes in NCI/MS were studied. The limits of detection (LODs, S/N = 3) ranged from 2.2 to 39.8 ng/kg. The average recoveries were between 71.1% and 121.4% at two spiked levels of 2 and 20 ng/g for both BDE-209 and DP and 0.2 and 2 ng/g for others with the relative standard deviations between 2.96% and 13.31%. The developed method has been successfully applied in the determination of PBDEs and DPs in several fish and fish oil supplements samples. The total PBDEs found ranged from 2.18 to 15.93 ng/g, and DP was not found. This method was validated to be accurate and sensitive for the trace analysis of PBDEs and DPs in the samples with fat.

A method for the detection of the alpha, beta and gamma-diastereoisomers of hexabromocyclododecane (HBCDs) in foods of animal origin, such as fish, chick, milk, butter etc., was developed using ultra performance liquid chromatography-electrospray ionization mass spectrometry (UPLC-ESI-MS) and isotope dilution. The HBCDs with the spiked isotopic 13C-HBCDs, the internal standards, were extracted using Soxhiet extraction, and further purified using acidic silica treatment and solid phase extraction. The separation of HBCDs was performed on Waters ACQUITY UPLC system with the column of BEH C8 and the gradient elution solvent of methanol-acetonitrile and water at a flow rate of 0.2 mL/min. The HBCDs were identified on the basis of the retention times and precursor ions, and quantitatively determined under the selected ion recording mode, m/z 640.7 for the [M-H]-ion. The limits of detection (LODs) of HBCDs ranged from 0.1 to 0.4 ng/g; and the limits of quantification (LOQs) ranged from 0.4 to 1.2 ng/g. The average recoveries ranged from 92.9% to 99.3% for the spiked levels of 0.6, 2.0 and 6.0 ng/g. with the relative standard deviations (RSDs) between 3.1% and 8.0%.