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ABSTRACT It remains inconclusive about the stability and optimal fixation scheme of screw internal fixation for lateral malleolus oblique fractures in clinical practice. In this study, the effects of different screw internal fixation methods on the biomechanics of lateral malleolus oblique fractures were investigated. These efforts are expected to lay a theoretical foundation for the selection of internal fixation methods and rehabilitation training regimens in the treatment of lateral malleolus fractures. A healthy ankle joint model and a lateral malleolus fracture internal fixation model were established based on CT data with the aid of some software. Besides, the effects of screw internal fixation modalities on the fracture displacement of fibula fractures, fibula Von Mises stress, and screw Von Mises stress under different physiological conditions and loading conditions were investigated using finite element methods (FEMs) and in vitro physical experiments. The double screw vertical fibular axis internal fixation approach had the lowest fracture displacement of fibula fractures and screw Von Mises stress values; while the double screw vertical fracture line internal fixation approach had the lowest fibula Von Mises stress values. Under different physiological conditions, the magnitude of the peak Von Mises stress of the fibula and screw was ranked as plantarflexion 20° > plantarflexion 10° > neutral position > dorsiflexion 10° > dorsiflexion 20°; and the magnitude of the peak displacement of the fibula fracture breaks was ranked as plantarflexion 20° > plantarflexion 10° > neutral position > dorsiflexion 20° > dorsiflexion 10°. The results of in vitro physical experiments and finite element analyses were in good agreement, which validated the validity of finite element analyses. The vertical fracture line screw implantation method displays a better load‐sharing ability; while the vertical fibular axis screw implantation method exhibits a better ability to prevent axial shortening of the fibula and also reduces the risk of screw fatigue damage. Overall, the double screw achieves better therapeutic effects than the single screw. Given that the ankle joint has high stability in the dorsiflexion position, it is recommended to prioritize dorsiflexion rehabilitation training, rather than dorsiflexion and plantarflexion rehabilitation training with too large angles, in the treatment of lateral malleolus fractures. [ABSTRACT FROM AUTHOR]

Intestinal absorption of compounds is significant in drug research and development. To evaluate this efficiently, a method combining mathematical modeling and molecular simulation was proposed, from the perspective of molecular structure. Based on the quantitative structure–property relationship study, the model between molecular structure and their apparent permeability coefficients was successfully constructed and verified, predicting intestinal absorption of drugs and interpreting decisive structural factors, such as AlogP98, Hydrogen bond donor and Ellipsoidal volume. The molecules with strong lipophilicity, less hydrogen bond donors and receptors, and small molecular volume are more easily absorbed. Then, the molecular dynamics simulation and molecular docking were utilized to study the mechanism of differences in intestinal absorption of drugs and investigate the role of molecular structure. Results indicated that molecules with strong lipophilicity and small volume interacted with the membrane at a lower energy and were easier to penetrate the membrane. Likewise, they had weaker interaction with P‐glycoprotein and were easier to escape from it and harder to export from the body. More in, less out, is the main reason these molecules absorb well. [ABSTRACT FROM AUTHOR]

Molecular switches that reversibly change their structures and physical properties are important for applications such as sensing and information processing at molecular scales. In order to avoid the intermolecular aggregation that is often detrimental to the stimuli‐responses of molecular switches, previous studies of molecular switches have been often conducted in dilute solutions which are difficult for applications in solid‐state devices. Here we report molecular design and synthesis that integrates anthraquinodimethane as molecular switching units into polymers with amenable processibility in solid states. Optical and electron spin resonance characterizations indicate that the four‐arm polymers of poly(ϵ‐caprolactone) or poly(D,L‐lactide) tethered from anthraquinodimethane slow down the dynamics of the conformational switching between the folded and the twisted conformations, enhance the photoluminescence in solid states and impart materials with a small energy gap from singlet ground state to thermally accessible triplet state. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that may progress to colorectal cancer in severe cases. Carnitine palmitoyltransferase‐1A (CPT1A) has been reported to be upregulated in colorectal cancer. This paper aims to explore the role of CPT1A in UC and its pathogenesis. An in vivo mice model of UC was constructed by administrating 3% dextran sulfate sodium (DSS). The expression level of CPT1A was examined by quantitative real‐time polymerase chain reaction and Western blot. The intestinal damage, inflammatory response and oxidative stress were assessed by hematoxylin and eosin staining, colon length, and commercial kits. Thereafter, an in vitro cell model of UC was established by stimulating HT‐29 cells with 2% DSS. The peroxisome proliferator‐activated receptor α (PPARα) signaling agonist GW7647 was used for treatment. Cell viability and apoptosis was assayed by cell counting kit‐8 assay and terminal dUTP nick‐end labeling assay, respectively. The inflammatory cytokines and oxidative stress‐related factors was evaluated using corresponding commercial detection kits. In DSS‐induced mice model of UC, CPT1A expression was upregulated. Interference of CPT1A attenuated histological damage, the disease activity index and colon length in colitis. We also found downregulation of CPT1A inhibited inflammatory response and oxidative stress, and inhibited PPARα signaling pathway in UC mice. Additionally, in DSS‐induced HT‐29 cells, downregulation of CPT1A promoted cell viability, reduced cell apoptosis, inflammatory response, and oxidative stress, which was partly abolished by additional treatment with GW7647. In summary, downregulation of CPT1A exerts a protective effect in DSS‐induced UC partially through suppressing PPARα signaling, suggesting that CPT1A might be a potential target for the treatment of UC. [ABSTRACT FROM AUTHOR]

Qu‐feng‐sheng‐shi Granules (QFSSG), a common prescription for the treatment of chronic inflammation and allergic rhinitis, is widely used in the clinic as a traditional Chinese medicine. Chemical analysis and quality control studies of this formulation are relatively limited compared with pharmacological studies. In this study, a high‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (HPLC–ESI–Q/TOF–MSn) was used to identify the components in this prescription. Next, to quantify six major compounds, an HPLC–UV method was developed and validated. The results showed that 53 compounds were identified based on the MSn data, retention time and previous reports, including 17 coumarins, 14 lignans, 10 chromones, nine phenylethanoid glycosides and three other compounds, were identified or tentatively assigned. Contents of six major bioactive compounds (4′‐O‐β‐glucopyranosyl‐5‐O‐methylvisamminol, Prim‐O‐glucosylcimifugin, forsythin, magnolin, imperatorin, isoimperatorin) could be determined by HPLC simultaneously. In addition, the potential anti‐inflammatory activity of six major compounds was determined too, and we found that four compounds (4′‐O‐β‐glucopyranosyl‐5‐O‐methylvisamminol, Prim‐O‐glucosylcimifugin, forsythin, imperatorin) have a potent nitric oxide inhibitory effect. In conclusion, this work provided comprehensive information on the quality control of QFSSG and evaluated the potential biological activity of the main components in QFSSG, which can contribute to understanding and using it more scientifically. [ABSTRACT FROM AUTHOR]

The concept of real-time release testing (RTRT) has recently been adopted by the production of pharmaceuticals in order to provide high-level guarantee of product quality. Process analytical technology (PAT) is an attractive and efficient way for realizing RTRT. In this paper, near-infrared (NIR) determination of cryptotanshinone and tanshinoneIIA content in tanshinone extract powders was taken as the research object. The aim of NIR analysis is to reliably declare the extract product as compliant with its specification limits or not. First, the NIR quantification method was developed and the parameters of the multivariate calibration model were optimized. The reliable concentration ranges covering the specification limits of two APIs were successfully verified by the accuracy profile (AP) methodology. Then, with the designed validation data from AP, the unreliability graph as the decision tool was built. Innovatively, the β-content, γ-confidence tolerance intervals (β-CTIs) around the specification limits were estimated. During routine use, the boundary of β-CTIs could help decide whether the NIR prediction results are acceptable. The proposed method quantified the analysis risk near the specification limits and confirmed that the unreliable region was useful to release the product quality in a real-time way. Such release strategy could be extended for other PAT applications to improve the reliability of results. [ABSTRACT FROM AUTHOR]

Borneol (BO) and menthol (MEN) are two widely used natural permeation enhancers in the transdermal drug delivery system. In previous studies, their permeation enhancement effects and mechanisms of action on the hydrophobic drug osthole (logP = 3.8) and hydrophilic drug 5‐fluorouracil (logP = −0.9) have been studied. In this study, ligustrazine (LTZ), whose logP is 1.3, was used as a model drug to provide a comprehensive understanding of the influence of its logP on the permeation‐enhancing effects of BO and MEN. Both BO and MEN enhanced the permeation of LTZ through the skin stratum corneum, as determined using the modified Franz diffusion cell experiment. The enhancement mechanisms were illustrated by coarse‐grained molecular dynamics simulations as follows: at low concentrations, the enhancing ratio of MEN was higher than that of BO because of the stronger perturbation effects of MEN on the lipid bilayer, making it looser and facilitating LTZ diffusion. However, at high concentrations, in addition to the diffusion mechanism, BO induced the formation of water channels to improve the permeation of LTZ; however, MEN had no significant effects through this mechanism. Their results were different from those found with osthole and 5‐fluorouracil and have been discussed in this study. Borneol (BO) and menthol (MEN) are two widely used natural permeation enhancers in the transdermal drug delivery system. In this paper, modified Franz diffusion cell experiments as well as a series of coarse‐grained molecular dynamic (CG‐MD) simulations were applied to study the permeation‐enhancing effects and mechanisms of different concentrations of BO and MEN on ligustrazine (LTZ). [ABSTRACT FROM AUTHOR]

ABSTRACT Waterborne polyurethane (WPU) has been intensively utilized as host materials for intrinsic conducting polymers. However, the stability and compatibility between polyaniline (PANI) and WPU remain a challenge for their composites. In this research, anionic-nonionic sulfonated waterborne polyurethane (SWPU) is adopted as matrix to prepare nanosized PANI- g-SWPU dispersions through chemical graft polymerization method, and the stability mechanism is systematically investigated. The PANI- g-SWPU dispersion is endowed with much higher stability and no PANI precipitation is detected after storage for 1 year when the PEG molecular weight is 1000 and R value is 1.2. The surface resistivity reaches the minimum when the graft time is 2.5 h, pH value is 2, n(APS)/ n(aniline) is 1, and the aniline content is 20 wt %. And the resistivity of the coated paper reaches 1.39 Ω cm, indicating that the as-prepared PANI- g-SWPU dispersion can be directly used as the antistatic coatings, which is also suitable for large scalable production. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45412. [ABSTRACT FROM AUTHOR]

Near-infrared chemical imaging (NIR-CI) is an emerging technology that combines traditional near-infrared spectroscopy with chemical imaging. Therefore, NIR-CI can extract spectral information from pharmaceutical products and simultaneously visualize the spatial distribution of chemical components. The rapid and non-destructive features of NIR-CI make it an attractive process analytical technology (PAT) for identifying and monitoring critical control parameters during the pharmaceutical manufacturing process. This review mainly focuses on the pharmaceutical applications of NIR-CI in each unit operation during the manufacturing processes, from the Western solid dosage forms to the Chinese materia medica preparations. Finally, future applications of chemical imaging in the pharmaceutical industry are discussed. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Chemical and physical quality attributes of herbal extract powders play an important role in the research and development of Chinese medicine preparations. The active pharmaceutical ingredients have a direct impact on the herbal extract’s efficacy, while the physical properties of raw material affect the pharmaceutical manufacturing process and the final products’ quality. In this study, tanshinone extract powders from Salvia miltiorrhiza which are widely used for the treatment of cardiovascular diseases in the clinic are taken as the research object. Both the chemical information and physical information of tanshinone extract powders are analyzed by near infrared (NIR) spectroscopy. The partial least squares (PLS) and least square support vector machine (LS-SVM) models are investigated to build the relationship between NIR spectra and reference values. PLS models performed well for the content of crytotanshinone, tanshinone IIA, the moisture, and average median particle size, while, for specific surface area and tapped density, the LS-SVM models performed better than the PLS models. Results demonstrated NIR to be a valid and fast process analytical technology tool to simultaneously determine multiple quality attributes of herbal extract powders and indicated that there existed some nonlinear relationship between NIR spectra and physical quality attributes. [ABSTRACT FROM AUTHOR]

This study demonstrated particle size effect on the measurement of saikosaponin A in Bupleurum chinense DC. by near infrared reflectance (NIR) spectroscopy. Four types of granularity were prepared including powder samples passed through 40-mesh, 65-mesh, 80-mesh, and 100-mesh sieve. Effects of granularity on NIR spectra were investigated, which showed to be wavelength dependent. NIR intensity was proportional to particle size in the first combination-overtone and combination region. Local partial least squares model was constructed separately for every kind of samples, and data-preprocessing techniques were performed to optimize calibration model. The 65-mesh model exhibited the best prediction ability with root mean of square error of prediction (RMSEP) = 0.492 mg·g−1, correlation coefficient RP=0.9221, and relative predictive determinant (RPD) = 2.58. Furthermore, a granularity-hybrid calibration model was developed by incorporating granularity variation. Granularity-hybrid model showed better performance than local model. The model performance with 65-mesh samples was still the most accurate with RMSEP = 0.481 mg·g−1, RP=0.9279, and RPD = 2.64. All the results presented the guidance for construction of a robust model coupled with granularity-hybrid calibration set. [ABSTRACT FROM AUTHOR]

It is imperfect to evaluate a subsampling variable selection method using only its prediction performance. To further assess the reliability of subsampling variable selection methods, dummy noise variables of different amplitudes were augmented to the original spectral data, and the false variable selection number was recorded. The reliabilities of three subsampling variable selection methods including Monte Carlo uninformative variable elimination (MC-UVE), competitive adaptive reweighted sampling (CARS), and stability CARS (SCARS) were evaluated using this dummy noise strategy. The evaluation results indicated that both CARS and SCARS produced more parsimonious variable sets, but the reliabilities of their final variable sets were weaker than those of MC-UVE. On the contrary, only marginal improvement on the prediction performance was obtained using MC-UVE. Further experiments showed that removing white noise-like variables beforehand would improve the reliability of variables extracted by CARS and SCARS. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

To transfer a calibration model in cases where the standardization samples are rare or unstable, a method based on orthogonal space regression (OSR) is proposed. It uses virtual standardization spectra to account for response changes between instruments or batches. A comparative study of the proposed OSR, piecewise direct standardization, finite impulse response, orthogonal signal correction, and model updating (MU) was conducted on both pharmaceutical tablet data and chlorogenic acid data. The results of these studies suggest that both the OSR and the MU are superior to the other transfer techniques in terms of root-mean-squared error of prediction and ratio of performance to interquartile distance. Moreover, OSR requires no identical standard samples, and it avoids re-optimizing the transfer models. In conclusion, both the differences among spectra measured on different spectrometers and the differences between different batches can be corrected successfully using the OSR method. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]