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The objective of this study was to evaluate the efficacy of various dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin against methicillin-resistant Staphylococcus aureus (MRSA) in neutropenic patients with cancer. Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to determine cumulative fraction of response (CFRs) in terms of area under the concentration-time curve/minimum inhibition concentration target. Currently clinical standard dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin were insufficient to provide expected CFRs against MRSA for neutropenic patients with cancer. The high dosing regimens of vancomycin (3500 mg/d), teicoplanin (800 mg/d) and daptomycin (8 mg/kg/d) could provide CFRs of ≥ 80%, showing a higher treatment success. However, the majority of CFRs with linezolid simulated dosing regimens reached < 80% against MRSA. Therefore, a strategy of high dosages of vancomycin, teicoplanin and daptomycin may be needed to attain optimal therapeutic efficacy against MRSA in neutropenic patients with cancer.

The objective of this study was to evaluate the efficacy of various daptomycin dosing regimens against Staphylococcus aureus and Enterococcus faecium in pediatric patients with proven/suspected gram-positive infection. Monte Carlo simulations (MCSs) were conducted using pharmacokinetic (PK) parameters and pharmacodynamic (PD) data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration (MIC) targets of daptomycin. According to the results of the MCSs, currently approved pediatric dosage regimens were sufficient against Staphylococcus aureus with MIC ≤ 0.5 μg/mL for all pediatric patients, but poor when MIC ≥ 1 μg/mL except for adolescents (12-17 years) who need a dosage of ≥10 mg/kg/day at MIC = 1 μg/mL. For Enterococcus faecium with MIC ≤ 4 μg/mL, the recommended dosage of 8-12 mg/kg/day in adults was enough for adolescents, but not subjected to younger pediatric patients. Furthermore, based on MIC distributions obtained from the European Committee on Antimicrobial Susceptibility Testing, the approved high-dose regimen should be recommended for infants aged 3-12 months, children (2-11 years), and adolescents to achieve better clinical efficacy against methicillin-resistant Staphylococcus aureus. In addition, the dosage of 8-12 mg/kg/day was powerful against Enterococcus faecium for adolescents; however, only the highest dosage of 12 mg/kg/day was effective for infants aged 3-12 months and children. All the simulated regimens were not optimal for infants aged 13-24 months. These PK/PD-based simulations rationalize and optimize the dosage regimens of daptomycin against Staphylococcus aureus and Enterococcus faecium in pediatric patients.

The aim of this study was to identify potential factors associated with insufficient/toxic voriconazole trough concentrations (VTCs) in patients in order to screen the high-risk population. A total of 119 VTCs were obtained from 67 patients. Multivariate regression analysis suggested that insufficient VTCs (1.0 mg/L) were significantly associated with younger age and underlying hematological malignancy, and toxic VTCs (5.5 mg/L) were significantly associated with lower serum albumin (ALB) level. Receiver operating characteristic curve analysis indicated that patients whose age47 years were the high-risk population of insufficient VTCs, and patients whose ALB27 g/L were the high-risk population of toxic VTCs. Younger age and underlying hematological malignancy were significant predictors of insufficient VTCs, and lower ALB level was found to be a significant predictor of toxic VTCs. Therefore, we recommend to increase the monitoring on these high-risk population to avoid treatment failure and to prevent toxic adverse events.

Acute lung injury (ALI) results from various factors including uncontrolled pulmonary inflammation, oxidative damage and the over-activated complement with high mortality rates. Jaceosidin was a flavonoid compound with significant anti-complement activity. We aimed to investigate the therapeutic effects of Jaceosidin on ALI induced by lipopolysaccharide (LPS). Mice were orally administrated with Jaceosidin (15, 30 and 60 mg/kg) after LPS challenge. 24 h after LPS challenge, Jaceosidin could significantly decrease the lung wet-to-dry weight (W/D) ratio and the protein concentration in bronchoalveolar lavage fluid (BALF). Jaceosidin could down-regulate the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), together with up-regulation the levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) in BALF. Jaceosidin could significantly decrease the levels of myeloperoxidase (MPO), cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB), COX-2 mRNA and NF-κB p65 mRNA together with increasing the activity of catalase (CAT). Additionally, Jaceosidin attenuated lung histopathological changes, inhibited the expressions of COX-2 and NF-κB p65 and reduced complement deposition with decreasing the levels of complement 3 (C3) and complement 3c (C3c) in serum. These data suggest that Jaceocidin may dampen the inflammatory response and decrease the levels of complement together with the antioxidant activity following LPS-induced ALI. Keywords: Jaceosidin, Acute lung injury, Complement, Inflammatory mediators, Oxyradicals

For grid structures, damages of structural members such as crookedness significantly affect the overall structural safety. Traditional assessment methods can hardly evaluate the impact of crooked members in existing grid structures accurately due to difficulties lying in crookedness measurement and residual load-bearing capacity analysis. In this paper, a new method of refined model adjustment and structural assessment with crooked tubular members of steel grid roofs taken into consideration is proposed, while the crooked measurement is conducted with an image-based 3D measurement method for the first time. Firstly, the original shape of crooked members is recovered using image-based 3D measurement method. Secondly, the measured deformation of the crooked members is adjusted from the load status at the time of measurement to the zero-load status in two ways. Finally, the FE model of the entire grid structure, together with the adjusted crooked tubular members is adopted in the residual load-bearing capacity analysis considering both geometric nonlinearity and material nonlinearity. A large span steel grid roof structure containing four crooked tubular members is utilized for the illustration and validation of the proposed methodology. The proposed method inventively offers a new direction for refined assessment of existing grid structures with crooked members and provides significant potential for practical implementation.

Phateacid esters (PAEs), such as dibutyl phthalate (DBP), have been widely used and human exposure results into serious toxic effects; such as the development of fatty liver disease. In the present study, SD rat models for in vivo study (normal and fatty liver model group) and hepatocytes for in vitro study (normal and abnormal lipid metabolism model group) were established to determine the effects of DBP on liver function and discover the possible mechanisms. Meanwhile, the peroxisome proliferator activated receptor (PPARα) blocker, GW6471, with the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activator, AICAR, were applied in vitro study to clarify the role of PPARα/SREBP-1c/FAS/GPAT/AMPK signal pathway in the process. Results suggested that DBP could activate PPARα signaling pathway and affected the protein expression of SREBP, FAS and GPAT to cause hyperlipidemia and abnormal liver function. DBP also could inhibit the phosphorylation and activation of AMPK to inhibit the decomposition and metabolism of lipids. Interestingly, the effects of DBP could be alleviated by GW6471 and AICAR. Our experimental results provide reliable evidence that DBP exposure could further induce liver lipid metabolism disorder and other hepatic toxicity through PPARα/SREBP-1c/FAS/GPAT/AMPK signal pathway.

The objective of this study was to evaluate the efficacy of various posaconazole dosing regimens of the different formulations against Aspergillus spp. in adults. Monte Carlo simulations were conducted using pharmacokinetic (PK) parameters and pharmacodynamic (PD) data to determine the probability of target attainment (PTA) and cumulative fraction of response (CFR) in terms of area under the concentration-time curve/minimum inhibition concentration (AUC/MIC) targets of posaconazole. According to the results of the PTA analysis, currently recommended clinical dosing regimens of the delayed-release tablet and intravenous (i.v.) solution were appropriate in prophylaxis against Aspergillus spp. with MICs ≤ 0.125 µg/mL. However, only high-dose regimens of the delayed-release tablet could achieve the target PTA in the treatment against Aspergillus spp. at an MIC of 0.125 µg/mL. Furthermore, the CFR was calculated for each dosing regimen. For the oral suspension, none of the simulated dosing regimens was effective against Aspergillus spp. For the delayed-release tablet and i.v. solution, the recommended dosing regimens were effective for prophylaxis of invasive fungal infections by four Aspergillus spp. (Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans and Aspergillus terreus). However, these recommended dosing regimens were only effective for the treatment of A. terreus infection. Therefore, the high-dose regimen (200 mg oral every 12 h) of the delayed-release tablet should be recommended to achieve optimal therapeutic efficacy against four Aspergillus spp. (A. flavus, A. fumigatus, A. nidulans and A. terreus). These PK/PD-based simulations rationalise and optimise the dosing regimens of the different posaconazole formulations against Aspergillus spp. in adults.

Sauropus spatulifolius Beille (named 'Long-Li-Ye' in China) is used to make 'herbal tea' to prevent pneumonia. This study aimed to evaluate the antioxidant activities in vitro and the protective effects of Long-Li-Ye on acute lung injury (ALI) induced by lipopolysaccharide (LPS).; Results: The supernatant after ethanol addition to Long-Li-Ye water extract (LLYCSL) and the resin eluting fraction of LLYCSL (LLY40) showed strong antioxidant activities in vitro. LLYCSL and LLY40 could attenuate ALI via decreasing myeloperoxidase activity, increasing superoxide dismutase activity and decreasing the levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and IL-6. In addition, LLY40 could increase catalase activity, increase the levels of IL-10, IL-4 and IL-13 and decrease the TNF-α/IL-10 ratio.; Conclusion: Long-Li-Ye could be used as a natural antioxidant for food production and functional food or dietary supplementation for people with ALI. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

Objective Oxaliplatin-induced peripheral neurotoxicity (OIPN) is the main limitation for its continuation in cancer patients. Traditional Chinese medicines (TCMs) have been used to prevent OIPN in China and have been demonstrated to be effective. However, due to the lack of direct comparison among TCMs, it remains unclear that which TCM is the best for OIPN prevention. Consequently, the present study aimed to compare the relative efficacies of TCMs to find out the best TCM by applying a network meta-analysis. Methods Studies were identified by searching PubMed, EMbase, Cochrane Libraries, CNKI, WanFang, and WeiPu database from January 1990 to May 2016. Randomized controlled trials (RCTs) that evaluated the efficacy of TCMs in preventing OIPN in cancer patients were included. Statistical analysis was performed with ADDIS 1.16.6. Results Twenty-five RCTs (1572 patients) involving five TCMs were included. The results of network meta-analyses showed that compared with oxaliplatin-based chemotherapy alone, the combination with Huangqi Injection (HQI), Shenmai Injection (SMI), Shenfu Injection (SFI), Buyang Huanwu Decoction (BHD), and Huangqi Guizhi Wuwu Decoction (HGWD) could decrease the overall OIPN incidence and the severe OIPN incidence in cancer patients. In addition, probability ranking results showed the order of efficacy in preventing overall OIPN incidence was HQI > HGWD > SFI = SMI > BHD, while the order of efficacy in preventing severe OIPN incidence was HQI > HGWD > BHD > SFI = SMI. Conclusion All five TCMs are effective neuroprotective agents against OIPN. Among these TCMs, HQI and HGWD were superior to others in clinical efficacy. Moreover, Astragalus membranaceus might be a more promising herb for the OIPN prevention. However, more direct head-to-head RCTs with high quality and large sample size are still needed to further confirm the conclusion.

Two new dibenzocyclooctadiene lignans, named schisantherin R (3) and schisantherin S (4), and six known compounds, named kadsuralignan I, kadsuralignan J, binankadsurin A, kadsuralactone B, acetyl-binankadsurin A, and dihydroguaiaretic acid, were isolated from the chloroform fraction of the ethanol extract of Kadsura coccinea (Lem.) A. C. Sm. The structures of the compounds were elucidated by spectroscopic analysis, including MS, CD, and 1D and 2D NMR spectra.

Objective To assess the efficacy and safety of berberine (BBR) in patients with type 2 diabetes mellitus (T2DM) by performing a systematic review. Methods PubMed, Cochrane Library, Embase, CNKI, and CBM were searched until May 2014. The randomized controlled trials (RCTs) of the effects of BBR on blood glucose in patients with T2DM were included. The quality of RCTs was assessed by the Jadad scale, and the Review Manager 5.1 software was used for data syntheses and analyses. Results Seventeen RCTs involving 1198 patients were included. The methodological quality of these RCTs was generally low. Compared with the control groups (placebo or no intervention with medicine), BBR suggested the statistically significant benefits in improving fasting blood glucose (FBG), postprandial blood glucose (PBG), glycosylated hemoglobin, and homeostasis model assessment of insulin resistance. Subgroups analysis of BBR compared with metformin (MET) showed that 1.5g/d MET was significantly better than BBR (0.9–.5 g/d) in lowering FBG and PBG. However, there was no significant difference between 1.5g/d BBR and 0.75g/d MET groups in blood glucose profiles. In comparison with rosiglitazone, BBR suggested the statistically significant benefits in lowering FBG. And there was no significant difference between BBR and glipizide groups in blood glucose profiles. In addition, the combination therapy of BBR and oral hypoglycemic agents had the advantages over oral hypoglycemic agents alone. No serious adverse effects of BBR have been reported. Conclusion BBR may have the beneficial effects in the control of blood glucose levels, though the efficacy of BBR is not superior to MET. BBR appeares to have advantages over rosiglitazone in improving FBG levels. In addition, the combination therapy of BBR and oral hypoglycemic agents may be a new attempt. However, the efficacy of BBR in patients with T2DM should be further evaluated by more RCTs in a larger population of patients.

CO2 capture and geologic sequestration represent one of the most promising options for reducing atmospheric emissions of CO2. Operator choices and subsurface uncertainties each have significant effects on avoiding the risk of triggering fault failure or intact rock failure that could lead to CO2 leakage. With the application of response surface methodology, a Box–Behnken design of experiments was utilized to evaluate the statistical significance of impact indicators, and uncertainty analysis was performed using a robust model to forecast the optimal combination of impact indicators for maintaining caprock integrity during CO2 injection in saline aquifers of the Ordos Basin, China. The Coulomb failure stress and vertical deformation of 130 statistically designed combinations were experimentally determined using numerical simulation. Then, according to the analysis of variance conducted for the response surface quadratic model, the burying depth, friction angle, Young's modulus, Poisson's ratio, and stress field, as well as quadratic terms such as burying depth ∗ friction angle and Poisson's ratio ∗ Poisson's ratio, were found to be highly significant with respect to the level of Coulomb failure stress. Among the variables, only burying depth was highly significant with respect to the level of vertical deformation. Furthermore, the results were analyzed and an optimal combination of impact indicators for Coulomb failure stress was determined according to the minimum Coulomb failure stress. The optimum combination had a desirability value of 1.000, which demonstrated the fitness of the selected statistical model in analyzing the experimental data.

The CO 2 geological storage in Ordos Basin and coal mining activities occurring simultaneously at the same location is a highly challenging coupled thermo-hydro-mechano-chemical (THMC) problem. To address this problem, an in-house program named “AEEA Coupler” was developed by linking two commercial software packages, Simulia ABAQUS and Schlumberger ECLIPSE, both of which are widely used and highly recognized in their respective fields. The applicability and accuracy of the developed coupler were tested by benchmark studies. A coupled multi-physics analysis was conducted based on real formation data of the Ordos and Shenhua CCS Demonstration Project with an injection rate of 0.1 Mtpa (Million tonnes per annum). A larger injection rate of 1.0 Mtpa was also investigated to explore the potential for the commercialization of large-scale CCS projects in the area. The primary conclusions that were obtained from the numerical simulations are as follows: (a) The pore pressure and displacement at the top of the reservoir increase with CO 2 injection, and the displacement continues to increase even after the termination of the CO 2 injection due to the coal mining activity. (b) The displacement of the wellbore peaks at the coal seam floor where the axial strain of the well soars abruptly. Our work suggests that the distance between coal pillars should be at least 90 m to ensure that the Mises stress of the casing is below the designed safe value. (c) The tensile stress and shearing stress increase significantly in the caprock as a result of the coupling of the two engineering activities; therefore, damages in the caprock occur more easily. (d) After CO 2 injection, only the strata with a depth of less than 769 m are affected by the coal mining activity. (e) The combined activities achieve a surface subsidence reduction comparable to that of only coal mining. Finally, several recommendations are given regarding the actual engineering implementation of the combined activities.

Tyre rolling resistance is very important to energy conservation and vehicle emissions. The main test methods of rolling resistance and their disadvantages are elaborated in this paper. In order to prepare for the (EC) No 1222/2009 and ECE R117, comparative analysis of ECE and GB are taken. It's important for the tyre company inboard export tyre to Europe. The influence of tyre pressure, test speed, load and environment temperature for the rolling resistance are studied, and lay the foundation for accurately measuring rolling resistance.

Mycorrhizas play a vital role in soil fertility, plant nutrition, and resistance to environmental stresses. However, mycorrhizal effects on plant resistance to herbivorous insects and the related mechanisms are poorly understood. This study evaluated effects of root colonization of tomato (Solanum lycopersicum Mill.) by arbuscular mycorrhizal fungi (AMF) Glomus mosseae on plant defense responses against a chewing caterpillar Helicoverpa arimigera. Mycorrhizal inoculation negatively affected larval performance. Real time RT-PCR analyses showed that mycorrhizal inoculation itself did not induce transcripts of most genes tested. However, insect feeding on AMF pre-inoculated plants resulted in much stronger defense response induction of four defense-related genes LOXD, AOC, PI-I, and PI-II in the leaves of tomato plants relative to non-inoculated plants. Four tomato genotypes: a wild-type (WT) plant, a jasmonic acid (JA) biosynthesis mutant (spr2), a JA-signaling perception mutant (jai1), and a JA-overexpressing 35S::PS plant were used to determine the role of the JA pathway in AMF-primed defense. Insect feeding on mycorrhizal 35S::PS plants led to higher induction of defense-related genes relative to WT plants. However, insect feeding on mycorrhizal spr2 and jai1 mutant plants did not induce transcripts of these genes. Bioassays showed that mycorrhizal inoculation on spr2 and jai1 mutants did not change plant resistance against H. arimigera. These results indicates that mycorrhizal colonization could prime systemic defense responses in tomato upon herbivore attack, and that the JA pathway is involved in defense priming by AMF.

Eupatorium lindleyanum DC., "Ye-Ma-Zhui" called by local residents in China, showed anti-inflammatory activity and is used to treat tracheitis. We had isolated and identified the flavonoids, diterpenoids and sesquiterpenes compounds from the herb. In the present study, we evaluated the protective effects of the flavonoids fraction of E. lindleyanum (EUP-FLA) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible underlying mechanisms of action. EUP-FLA could significantly decrease lung wet-to-dry weight (W/D) ratio, nitric oxide (NO) and protein concentration in BALF, lower myeloperoxidase (MPO) activity, increase superoxide dismutase (SOD) activity and down-regulate the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Additionally, EUP-FLA attenuated lung histopathological changes and significantly reduced complement deposition with decreasing the levels of Complement 3 (C3) and Complement 3c (C3c) in serum. These results demonstrated that EUP-FLA may attenuate LPS-induced ALI via reducing productions of pro-inflammatory mediators, decreasing the level of complement and affecting the NO, SOD and MPO activity.

Common mycorrhizal networks (CMNs) are the underground conduits of nutrient exchange between plants. However, whether the CMNs can serve as the underground conduits of chemical communication to transfer the disease resistance signals between plants are unknown. By inoculating arbuscular mycorrhizal fungus (AMF) Glomus mosseae to establish CMNs between 'donor' and 'receiver' tomato plants, and by inoculating Alternaria solani, the causal agent of tomato early blight disease, to the 'donor' plants, this paper studied whether the potential disease resistance signals can be transferred between the 'donor' and 'receiver' plants roots. The real time RT-PCR analysis showed that after inoculation with A. solani, the AMF-inoculated 'donor' plants had strong expression of three test defense-related genes in roots, with the transcript levels of the phenylalanine ammonia-lyase (PAL), lipoxygenase (LOX) and chitinase (PR3) being significantly higher than those in the roots of the 'donor' plants only inoculated with A. solani, not inoculated with both A. solani and AMF, and only inoculated with AMF. More importantly, in the presence of CMNs, the expression levels of the three genes in the roots of the 'receiver' plants were significantly higher than those of the 'receiver' plants without CMNs connection, with the connection blocking, and with the connection but the 'donor' plants not A. solani-inoculated. Compared with the control (without CMNs connection), the transcript level of the PAL, LOX and PR3 in the roots of the 'receiver' plants having CMNs connection with the 'donor' plants was 4.2-, 4.5- and 3.5-fold higher, respectively. In addition, the 'donor' plants activated their defensive responses more quickly than the 'receiver' plants (18 and 65 h vs. 100 and 140 h). These findings suggested that the disease resistance signals produced by the pathogen-induced 'donor' tomato plant roots could be transferred to the 'receiver' plant roots through CMNs.

Arbuscular mycorrhiza (AM) can not only improve host plants nutrient absorption, but also enhance their disease resistance. Taking the tomato (Lycopersicon esculentum) seedlings preinoculated with axbuscular mycorrhizal fungus (AMF) Glomus versiforme as test materials, this paper studied their protective enzyme activities and defense-related genes expression, and their resistance against a fungal pathogen Alternaria solani Sorauer which causes early blight. The seedlings pre-inoculated with AMF and later inoculated with A. solani showed significantly higher activities of superoxide dismutase (SOD) and peroxidase (POD) in leaves. The leaf SOD activity of the dually inoculated plants reached the maximum 18 h after pathogen inoculation, being 28.6%, 79.2% and 82.8% higher than that of the plants with G. versiforme inoculation alone, pathogen inoculation alone, and non-inoculation, and the Leaf POD activity reached the maximum 65 h after pathogen inoculation, being 762%, 18.3%, and 1710% higher, respectively. Real time RT-PCR analysis showed that dual inoculation with C. versiforme and A. solani strongly induced the expression of three defense-related genes. The transcript levels of pathogen-related protein (PR1), basic type beta-1,3-glucanase (PR-2), and chitinase (PR-3) in leaves were 9.67-, 8.54-, and 13.4-fold higher, as compared with the non-inoculation control, respectively. Bioassay showed that the disease incidence and disease index of the seedlings pre-inoculated with C. versiforme were reduced by 36.3% and 61.4%, respectively, as compared with the non-mycorrhizal control plants. These findings indicated that mycorrhizal colonization could induce stronger and quicker defense responses of host tomato plants, and priming could be an important mechanism of the enhanced disease resistance of mycorrhizal tomato plants.