Predictive Model of Oxaliplatin-induced Liver Injury Based on Artificial Neural Network and Logistic Regression.

Background and Aims: Identifying potential high-risk groups of oxaliplatin-induced liver injury (OILI) is valuable, but tools are lacking. So artificial neural network (ANN) and logistic regression (LR) models will be developed to predict the risk of OILI. Methods: The medical information of patients treated with oxaliplatin between May and November 2016 at 10 hospitals was collected prospectively. We used the updated Roussel Uclaf causality assessment method (RUCAM) to identify cases of OILI and summarized the patient and medication characteristics. Furthermore, the ANN and LR models for predicting the risk of OILI were developed and evaluated. Results: The incidence of OILI was 3.65%. The median RUCAM score with interquartile range was 6 (4, 9). The ANN model performed similarly to the LR model in sensitivity, specificity, and accuracy. In discrimination, the area under the curve of the ANN model was larger (0.920>0.833, p=0.019). In calibration, the ANN model was slightly improved. The important predictors of both models overlapped partially, including age, chemotherapy regimens and cycles, single and total dose of OXA, glucocorticoid drugs, and antihistamine drugs. Conclusions: When the discriminative and calibration ability was given priority, the ANN model outperformed the LR model in predicting the risk of OILI. Other chemotherapy drugs in oxaliplatin-based chemotherapy regimens could have different degrees of impact on OILI. We suspected that OILI may be idiosyncratic, and chemotherapy dose factors may be weakly correlated. Decision making on prophylactic medications needs to be carefully considered, and the actual preventive effect needed to be supported by more evidence.

Quality Evaluation of Ophiopogon japonicus from Two Authentic Geographical Origins in China Based on Physicochemical and Pharmacological Properties of Their Polysaccharides.

Ophiopogon japonicus is widely used as a tonic herb in China. According to the origins, MaiDong of Chinese materia medica can be classified as Zhe MaiDong (Ophiopogon japonicus in Zhejiang), Chuan MaiDong (Ophiopogon japonicus in Sichuan), Duanting Shan MaiDong (Liriope muscari), and Hubei MaiDong (Liriope spicata). In terms of quality control, polysaccharides-based evaluations have not yet been conducted. In this study, microwave-assisted extraction (MAE) was used for the preparation of polysaccharides from 29 batches of MaiDong. HPSEC-MALLS-RID and HPAEC-PAD were employed to investigate their molecular parameters and compositional monosaccharides, respectively. The ability to scavenge ABTS radicals and immune promotion abilities, in terms of nitric oxide releasing and phagocytosis on RAW 264.7 macrophages, were also compared. The results showed that polysaccharides in different MaiDong varied in molecular parameters. All polysaccharides mainly contained fructose and glucose with small amounts of arabinose, mannose, galactose, and xylose. For polysaccharides of Zhe MaiDong and Chuan MaiDong, the molar ratio of Fru to Glc was roughly 15:1 and 14:1, respectively. Zhe MaiDong exhibited better antioxidant and immune promotion activity, and so did that of fibrous roots. The pharmacological activity, however, did not account for the variation in growth years. Finally, indicators for quality control based on multivariate statistical analysis included: yield, antioxidant activity, the content of fructose, and RI signal. It was concluded that MaiDong's fibrous roots had similar components to the root, and their quality was not significantly affected by growth age. This may provide some guidance for the cultivation and use of MaiDong.

Effects of steam on polysaccharides from Polygonatum cyrtonema based on saccharide mapping analysis and pharmacological activity assays.

BACKGROUND: Polygonatum cyrtonema, one of origins of Polygonata Rhizoma (HuangJing in Chinese), is traditionally steamed repeatedly before being used as herbal medicine in China. However, there has no standard for steaming of HuangJing. Therefore, a comprehensive study for effects of steam on polysaccharides from Polygonatum cyrtonema based on saccharide mapping, a powerful method developed for polysaccharides analysis, and pharmacological activity are still necessary, which is helpful to explore the effect of steam on the physiochemical and biological activities of its polysaccharides and develop steaming standard of Polygonatum cyrtonema. METHODS: To explore the effect of steam on physiochemical and biological activities of P. cyrtonema polysaccharides (PCP), six polysaccharides named PCP0, PCP1, PCP2, PCP3, PCP4 and PCP5 were extracted from the herb consecutively steamed for 0-5 times, respectively. Their molecular weight distribution, monosaccharide composition and PACE fingerprints were investigated through HPSEC-MALLS-RID, HPAEC-PAD and saccharide mapping based on polysaccharides analysis by using carbohydrate gel electrophoresis (PACE) and HPTLC, respectively. In addition, their antioxidant ability and immunostimulatory activities on RAW 264.7 cells in terms of NO production and phagocytosis were compared. RESULTS: Results suggested that molecular weights could be changed during steam, which increased by first steaming and then decreased with further steaming though all polysaccharides' molecular weights were 105-107 Da. They all showed irregularly spherical conformation in aqueous solution based on AFM imaging. Their monosaccharide composition and PACE fingerprints were significantly different after steaming, i.e., galactose increased while glucose and mannose decreased, and ß-1,4-Galp appeared while ß-1,4-Manp increased, after steaming. Steamed PCP significantly increased scavenging activity against ABTS radicals, while PCP0 had the best immunostimulatory effect on RAW 264.7 in terms of NO production and phagocytosis. CONCLUSIONS: In summary, steam significantly affected the chemical composition and bioactivities of polysaccharides from P. cyrtonema. Considering the balance beneficial effects of steaming on antioxidant and immunopotentiation activities of PCP, 2 times of continuous steam is the optimal choice under the given conditions.

Uniaxial tensile deformation and fracture process of structures forming by unsaturated intercalation of amine molecule into C-S-H gel.

The application of cement-based materials in engineering requires the understanding of their characteristics and subsequent deformation and fracture process of C-S-H gel in service. In this work, three types of amine molecules including tetraethylenepentamine (TEPA), polyacrylamide (PAM), and triethanolamine (TEA) were intercalated into C-S-H gel in an unsaturated status successfully. Systematical analysis was performed on the structures and properties for both C-S-H gel and corresponding amine molecules/C-S-H gel. It was found that the unsaturated intercalation of amine molecules into C-S-H gel plays a key role in the geometry and therein density of nanocomposites. Subsequently, radial distribution function (RDF), time-correlated function (TCF), and mean square displacement (MSD) were applied to characterize the structure and dynamic information of the as-generated nanocomposites, demonstrating the occurrence of interaction between amine molecules with Ca-Si layer and acceleration of water diffusion by unsaturated intercalation of amine molecules into the interlayer region in C-S-H gel. Finally, the deformation and fracture process of C-S-H gel and amine molecules/C-S-H gel under uniaxial tensile loads were given by molecular dynamics simulation. It was indicated that the tangent modulus of nanocomposites demonstrates a strain-softening nature, indicating a visco-elastic behavior. The breakage of Ca-O bonds and hydrogen bonds dominates the fracture of C-S-H gel. Weak interaction for TEPA/C-S-H gel or TEA/C-S-H gel leads to a decreased tensile strength. Local stress concentration in other interlayer region governs the deformation and fracture process in spite of the formation of strong interaction between double bonded polar oxygen atoms in PAM molecules and Ca atoms in C-S-H gel.

Effect of Dodecyl Trimethyl Ammonium Bromide on the Migration of Water Molecules in the Pores of Lignite: An Experimental and Molecular Simulation Study.

Molecular dynamics simulations and experiments were used to study the influence of dodecyl trimethyl ammonium bromide (DTAB) on the migration of water molecules in the pores of lignite. To simulate the accuracy, 13C NMR was used to confirm the structure of Shengli lignite. It was found through adsorption experiments that DTAB reduces the specific surface area and pore volume of lignite. Molecular simulations indicate that the lignite and water molecules are primarily connected by hydrogen bonding. DTAB impedes the movement of water molecules in the pores of lignite and the storage space of compressed water molecules. Water molecules are mainly present in the pores of lignite in a posture parallel to the XOY plane, which facilitates the formation of hydrogen-bonding networks. However, this also leads to a decrease in the mobility of water molecules. Experimental and simulation results show that DTAB can enter lignite pores, reducing the water absorption in lignite. This is highly significant for the processing and utilization of lignite.