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To obtain radiation pressure of a hybrid chiral structure, we derive the transfer matrix method and optical force densities from the Maxwell stress tensor for a planar layered bianisotropic media. The key derivations are how to get wavevectors and field components of each layer, transfer matrices connecting four eigenwaves of adjacent chiral media, as well as the force densities expressed by co- and cross-polarized reflection and transmission coefficients. After the validation of the methods and programs is performed, the radiation pressure of a layered biaxial bianisotropic chiral slab is studied. The effects of linearly and circularly polarization incident waves, incident angle, thickness, opposite handedness (optical activity), anisotropy, gain and loss of chiral media on the radiation pressure are discussed. Our work elucidates the mechanism of light-chiral media interactions, provides better understanding of chiral detection, optical trapping, and biophysics.

Background: The trough concentration (Cmin) of Imatinib (IM) is closely related to the treatment outcomes and adverse reactions of patients with gastrointestinal stromal tumors (GIST). However, the drug plasma level has great inter- and intra-individual variability, and therapeutic drug monitoring (TDM) is highly recommended. Objective: To develop a novel, simple, and economical two-dimensional liquid chromatography method with the ultraviolet detector (2D-LC-UV) for simultaneous determination of IM and its major active metabolite, N-desmethyl imatinib (NDIM) in human plasma, and then apply the method for TDM of the drug. Methods: The sample was processed by simple protein precipitation. Two target analytes were separated on the one-dimension column, captured on the middle column, and then transferred to the two-dimension column for further analysis. The detection was performed at 264 nm. The column temperature was maintained at 40˚C and the injection volume was 500 μL. Totally 32 plasma samples were obtained from patients with GIST who were receiving IM. Results: IM and NDIM were separated well from other impurities and the entire analytical time for each run was 12.0 min. The calibration curves had good linearity in the range of 33.5-2678.4 ng/mL for IM, and 20.0-1600.0 ng/mL for NDIM, respectively. The extraction efficiency was more than 95%. The acceptable accuracy, precision, recovery and stability were also obtained. The Cmin of the drug in patients was measured with the validated method. Conclusion: The novel 2D-LC-UV method is simple, stable, highly automated and independent of specialized technicians, which greatly increases the real-time capability of routine TDM for IM in hospital.

Introduction: Drug-induced acute kidney injury (D-AKI) is one of the important types of AKI. The incidence of D-AKI in China has rarely been studied. Objective: This study aims to explore the disease burden, related drugs, and risk factors of D-AKI. Methods: A nationwide cross-sectional survey was conducted in adult patients from 23 academic hospitals in 17 provinces in China. Suspected AKI was screened based on serum creatinine changes in accordance with the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for AKI, patients who met the diagnosis of hospital-acquired AKI in January and July of 2014 were defined. Suspected AKI was firstly evaluated for the possibility of D-AKI by pharmacists using the Naranjo Scale and finally defined as D-AKI by nephrologists through reviewing AKI clinical features. Results: Altogether 280,255 hospitalized patients were screened and 1,960 cases were diagnosed as hospital-acquired AKI, among which 735 cases were defined as having D-AKI (37.50%, 735/1,960) with an in-hospital mortality rate of 13.88% and 54.34% of the survivors did not achieve full renal recovery. 1,642 drugs were related to AKI in these patients. Anti-infectives, diuretics, and proton pump inhibitors were the top 3 types of drugs relevant to D-AKI, accounting for 66.63% cumulatively. Besides age, AKI staging, severe disease, hypoalbuminemia, plasma substitute, and carbapenem related D-AKI were independent risk factors for in-hospital mortality of D-AKI patients. Conclusion: In China, D-AKI has caused a substantial medical burden. Efforts should be made to pursue nephrotoxic drug stewardship to minimize attributable risk and improve the prevention, diagnosis, and treatment of D-AKI.

An LC-MS/MS method was developed for simultaneous determination of voriconazole and its main metabolite voriconazole N-oxide in human plasma. Plasma pretreatment was simple one-step protein precipitation with acetonitrile, and separation was achieved on a Hypersil GOLD aQ column. A triple-quadrupole tandem mass spectrometer with electrospray ionization source was operated by multiple reaction monitoring (MRM) in positive ion mode, and the precursor–product ion pairs used for MRM were m/z 350.1→281.0, 365.8→224.1, and 531.3→489.2 for voriconazole, voriconazole N-oxide, and internal standard, respectively. The total analytical run time was 6 min. The proposed method was linear over the range 0.001–1 µg/mL for voriconazole and voriconazole N-oxide. The lower limit of quantification was 1 ng/mL for both of them. The specificity, accuracy, precision, recovery, matrix effect, stability as well as dilution integrity of this method were within acceptable limits during validation period. This method was su...

Background: Antidepressants and antipsychotics are widely prescribed drugs for the treatment of mental diseases. Therapeutic drug monitoring (TDM) is recommended for patients taking these drugs to ensure pharmaceutical efficacy, medication compliance and prevent toxicity. Objective: An ultra-high performance liquid chromatography/tandem-mass spectrometry (UPLC-MS/ MS) method was developed for simultaneous determination of two Antidepressants-Fluoxetine (FLU) and Escitalopram (ESC), and two antipsychotics-risperidone (RIS) and aripiprazole (ARI), in human plasma. Methods: The sample was processed by simple protein precipitation and the targeted analytes were separated on a C18 column by gradient elution with a mobile phase containing 0.1% formic acid (v/v) and acetonitrile. All the analytes were qualitative and quantitative measured by electrospray ionization source with Multiple Reaction Monitoring (MRM) in positive ion mode. A total of 56 plasma samples were obtained from out- or in-patients who were taking the cited four drugs for further analysis. Results: The calibration curves for FLU, ESC, RIS and ARI were linear in the range of 45-1800, 4-320, 2-200 and 50-1800 ng/mL, respectively. The entire analytical time for the analytes was 7.0 min for each run and the extraction efficiency was more than 90%. The sample was stable within various storage conditions. The trough concentrations in patients were measured with the validated method. Conclusions: The developed method was successfully used for simultaneous determination of FLU, ESC, RIS and ARI in the plasma of the patients, which provides effective technical support for routine TDM of these four drugs and is of great clinic value for individual therapy.

A series of 2-phenoxy-N-phenylacetamides were designed and synthesized with a view to develop novel anticancer agents. All compounds were prepared with varied substitutions in the phenyl ring of aniline and evaluated for their anticancer activity. The majority of them displayed a moderate degree of cytotoxicity against several human cancer cell lines. Six compounds displayed potent cell growth inhibitory activity with IC50 values below 20 μM. Two compounds (TC-5 and TC-14) exhibited the most pronounced antiproliferative activity equivalent to or higher than that of positive control. The structure – activity relationship of these anticancer agents has been reviewed. The results indicate that incorporation of halogen into the benzene ring is beneficial for anticancer activity.

Recently approved multi-target inhibitors of receptor tyrosine kinases (RTKs) have significantly improved the clinical treatment of cancers. A series of N,N′-diarylureas incorporated with aromatic heterocycle have been designed, synthesized and evaluated as novel multi-target RTK inhibitors. The preliminary biological evaluation indicated that several compounds exhibited comparable potency with Sorafenib. Among them, compound 6f was identified as the most potent multikinase inhibitor of EGFR, KDR and FGFR1 with IC50 values of 14.83 nM, 21.57 nM, and 28.23 nM, respectively. These compounds expanded the structural diversity of diarylureas as RTK inhibitors. The results demonstrated that compound 6f could be served as novel lead compound for further development of multi-target RTK inhibitors.

Twenty chalcone derivatives were designed and synthesized with a view to developing novel anticandidal agents. All the compounds were evaluated for their antifungal activity against Candida albicans (ATCC 10231 and ten clinical isolates). Most of them exhibited moderate anticandidal potency with MIC values ranging from 2.0 to 32.0 μg/mL. Four compounds (T4, T6, T19, T20) displayed potent anticandidal activity with MIC values of 2.0 μg/mL. Compound T6 showed the most potent activity against Candida albicans (ATCC 10231 and four clinical isolates). In addition, attempts have also been made to correlate anticandidal activity to physicochemical properties. The results indicated that incorporation of halogen on the benzene ring is beneficial for anticandidal activity.

Rationale A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for quantification of caspofungin in dried blood spots (DBS) was developed and validated. Methods The DBS samples were prepared by spotting whole blood onto Whatman 903 filter paper, drying at room temperature and extracting with 50% methanol and further cleaned by protein precipitation with acetonitrile. Roxithromycin was selected as internal standard, and the separation of the analytes with endogenous ingredients was accomplished on a Hypersil GOLD aQ column with a mobile phase composed of 0.1% formic acid (v/v) and methanol in gradient mode. The detection of the analytes was performed on a triple quadrupole mass spectrometer in positive electrospray ionization mode, and the following selective reaction monitoring (SRM) transitions were monitored: m/z 547.6 → 538.7 and 837.4→ 679.4 for quantification of caspofungin and the internal standard, respectively. Results The total analytical time was 8 min for each run. The calibration curve exhibited a good linearity over the range from 0.2 to 20 μg/mL and the lower limit of quantification (LLOQ) was 0.2 μg/mL for caspofungin in DBS. The recoveries of caspofungin ranged from 62.64% to 76.69%, and no obvious matrix effect was observed. The intra- and inter-day precision and accuracy were within acceptable limits, and caspofungin in DBS was stable after storage at room temperature for 24 h and at -80°C for 30 days. There was no evident effect of the hematocrit value on the analysis of caspofungin. Conclusions The proposed method presents an alternative to the conventional venous sampling method, and was successfully utilized for pharmacokinetics study of caspofungin in ICU patients.

Background and Aims Metal (e.g. Cd and Pb) pollution in agricultural soils and crops have aroused considerable attention in recent years. This study aimed to evaluate the effects of ROL and Fe plaque on Cd and Pb accumulation and distribution in the rice plant.

A series of N,N'-dibenzoylpiperazine derivatives incorporated with 1H-indazol-3-amine have been designed, synthesized and evaluated as novel Bcr-Abl inhibitors. Several title compounds exhibited potent inhibitory activity against Bcr-Abl wild type as well as T315I mutant. Two compounds, 11a and 12c, strongly suppressed the activity of native and mutant Bcr-Abl. In particular, 11a exhibited comparable potency with that of Imatinib. It potently inhibited both Bcr-Abl(WT) and Bcr-Abl(T315I) with IC50 values of 0.014 μM and 0.45 μM, respectively. Furthermore, compound 11a also inhibited the proliferation of K562 leukemia cancer cells. Therefore, it could serve as promising lead compound for further optimization of Bcr-Abl(WT) and Bcr-Abl(T315I) inhibitors.

Influenza is an infection of the upper respiratory tract caused by influenza virus. Neuraminidase (NA) plays an essential role in replication and infection of influenza virus. It is considered as a suitable target for antivirus agents development. Several potent NA inhibitors (NAIs) developed by using structure-based rational design have been widely used in clinic for treatment of influenza. However, the emergence of NA inhibitor-resistant virus mutations significantly limit their effectiveness. The molecular basis of virus resistance to NAIs has been a focus of intensive research. This review highlights recent progress in rational design and resistance mechanism of NAIs. We hope this review will be useful to not only researchers who are interested in developing novel NAIs but also clinical pharmacists.

Tubulin protein is one of several members of a small family of globular proteins. It offers a potential target for anticancer drug design and development. Combretastatin A-4 (CA-4) is a potent anticancer and antiangiogenesis natural substance isolated from Combretum caffrum. Modifications on the CA-4 structure have led to a great number of novel CA-4 derivatives as potent tubulin inhibitors and high cytotoxic anticancer agents is becoming an interesting field, leading to a breakthrough in the treatment of cancer. In this review, the recent developments of novel CA-4 derivatives via the modifications on the A- and B-ring and the double bond as anticancer agents are discussed.

Focused on the problem of distortion correction for those images having simple contour, the synthetic method was described. In advance, without known camera parameters and any known world coordinates point in 3D space, the first order radial distortion coefficient can be estimated based on the fundamental property: a camera follows the pinhole model if and only if the projection of every line in space onto the camera is a line. Then the proposed distortion correction method, which characterized by its fast computing speed and good accuracy, maps not only pixel coordinates but also the grey values between the distortion image and non-distortion image. Several experiments and analysis were performed and presented on this paper. Finally, a comparative analysis about the accuracy and computational load with real data between this new method and the existed methods was put forward.