A Survey of Latest Wi-Fi Assisted Indoor Positioning on Different Principles.

As the location-based service (LBS) plays an increasingly important role in real life, the topic of positioning attracts more and more attention. Under different environments and principles, researchers have proposed a series of positioning schemes and implemented many positioning systems. With widely deployed networks and massive devices, wireless fidelity (Wi-Fi) technology is promising in the field of indoor positioning. In this paper, we survey the authoritative or latest positioning schemes for Wi-Fi-assisted indoor positioning. To this end, we describe the problem and corresponding applications, as well as an overview of the alternative methods. Then, we classify and analyze Wi-Fi-assisted indoor positioning schemes in detail, as well as review related work. Furthermore, we point out open challenges and forecast promising directions for future work.

Development and validation of a liquid chromatography/tandem mass spectrometry method for determination of caspofungin in dried blood spots.

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 â†’ 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.

Expanding the structural diversity of diarylureas as multi-target tyrosine kinase inhibitors.

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 14.83nM, 21.57nM, and 28.23nM, 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.

[Chemical Constituents from Infructescence of Platycarya strobilacea].

Objective: To study the chemical constituents of the chloroform and acetic ether fractions from infructescence of Platycarya strobilacea. Methods: The compounds were isolated and purified by various chromatographic methods. Spectral analysis were taken to identify the structures. Results: Eleven compounds were isolated and identified as dotriacontane( 1), ursolic acid( 2),hexacosene( 3),ß-sitosterol( 4),daucosterol( 5),2,5,8-trihydroxy-3-methoxy-1,4-naphthalenedione( 6),3,3'-dimethoxyellagic acid( 7),ellagic acid( 8),4'-hydroxyisoflavone-7-O-ß-D-galactoside( 9),3,3'-dimethoxyellagic acid-4'-O-ß-D-xylopyroside( 10), gallic acid( 11). Conclusion: Compounds 1,3 ~ 6,9,10 are isolated from this genus for the first time, compounds 1 ~ 6,9,10 are isolated from this plant for the first time.

Metabolic and pharmacokinetic studies of scutellarin in rat plasma, urine, and feces.

AIM: To study the metabolic and pharmacokinetic profile of scutellarin, an active component from the medical plant Erigeron breviscapus (Vant) Hand-Mazz, and to investigate the mechanisms underlying the low bioavailability of scutellarin though oral or intravenous administration in rats. METHODS: HPLC method was developed for simultaneous detection of scutellarin and scutellarein (the aglycone of scutellarin) in rat plasma, urine and feces. The in vitro metabolic stability study was carried out in rat liver microsomes from different genders. RESULTS: After a single oral dose of scutellarin (400 mg/kg), the plasma concentrations of scutellarin and scutellarein in female rats were significantly higher than in male ones. Between the female and male rats, significant differences in AUC, t(max2) and C(max2) for scutellarin were found. The pharmacokinetic parameters of scutellarin in the urine also showed significant gender differences. After a single oral dose of scutellarin (400 mg/kg), the total percentage excretion of scutellarein in male and female rats was 16.5% and 8.61%, respectively. The total percentage excretion of scutellarin and scutellarein in the feces was higher with oral administration than with intravenous administration. The in vitro t(1/2) and CL(int) value for scutellarin in male rats was significantly higher than that in female rats. CONCLUSION: The results suggest that a large amount of ingested scutellarin was metabolized into scutellarein in the gastrointestinal tract and then excreted with the feces, leading to the extremely low oral bioavailability of scutellarin. The gender differences of pharmacokinetic parameters of scutellarin and scutellarein are due to the higher CL(int) and lower absorption in male rats.

Drug-Induced Hospital-Acquired Acute Kidney Injury in China: A Multicenter Cross-Sectional Survey.

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.

[Absorption and transportation characteristics of scutellarin and scutellarein across Caco-2 monolayer model].

OBJECTIVE: To investigate the absorption and transepithelial transport characteristics of scutellarin and scutellarein in the human colonic adenocarcinoma cell (Caco-2) monolayer model. The influence factors on these two compounds' absorption were investigated, such as buffer solution, duration of culture, and inhibitors of multidrug resistance-associated protein 2 (MRP(2)), breast cancer drug resistance protein (BCRP) and P-glycoprotein (P-gp). METHODS: By using Caco-2 monolayer as an intestinal epithelial cell model, the transport process was studied from apical (AP) side to basolateral (BL) side or from BL to AP. The two compounds were determined by high-performance liquid chromatography coupled with diode-array-detector detection. Transport parameters and apparent permeability coeffients (P(app)) were calculated. RESULTS: The P(app) values of scutellarin and scutellarein were different in two buffer solutions, respectively. In phosphate buffered saline, scutellarin had no absorption from AP to BL, while its P(app) value was 0.74×10(-6) to 1.58×10(-6) cm/s from BL to AP. The P(app) values of scutellarein were 4.33×10(-6) to 6.79×10(-6) cm/s and 1.32×10(-6) to 2.56×10(-6) cm/s from AP to BL and from BL to AP, respectively. The P(app) value gradually decreased with time. The absorption of scutellarein was better than that of scutellarin. The scutellarin absorption was improved by verapamil, MK-571 and reserpine. The scutellarein absorption was improved by verapamil whereas its excretion was improved by MK-571. CONCLUSION: Absorption of scutellarin is difficult in Caco-2 monolayer cells, which contributes to its low bioavailability. Scutellarein absorption is better than scutellarin absorption. Scutellarein transepithelial transport is passive diffusion. The inhibitor of P-gp can improve scutellarin and scutellarein transportation. The inhibitors of MRP(2) and BCRP can promote transportation of scutellarin. The inhibitor of MRP(2) can promote efflux of scutellarein. The multidrug resistance-associated protein may be the second reason for low bioavailability of scutellarin.

A UPLC-MS/MS Assay for Simultaneous Determination of Two Antipsychotics and Two Antidepressants in Human Plasma and Its Application in Clinic.

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. CONCLUSION: 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.

[Pharmacokinetic and tissue distribution study of scutellarin in rats].

OBJECTIVE: To investigate the pharmacokinetic and distribution character of scutellarin in plasma and tissues in rats, in order to provide some references for rational drug use in the clinic. METHOD: The solution of scutellarin was administered to rats (80 mg x kg(-1)) by oral gavage. A high performance liquid chromatography method determinated the scutellarin concentration in rat plasma and tissue. The plasma samples were performed by solid phase extraction method. The other biological samples were extracted by ethyl acetate. RESULT: The range of scutellarin in plasma and tissue in rats were 10-1280 ng x mL(-1) (R2 > 0.99), 40-1280 ng x g(-1) (R2 > 0.99), respectively. The lowest detection of scutellarin were 10 ng x mL(-1) and 40 ng x g(-1), the precision were less than 8%. The main pharmacokinetic parameters of scutellarin were as follows: tmax, Cmax, AUC and MRT being (7.7 +/- 0.9) h, (288.0 +/- 75.2) microg x L(-1), (5.6 +/- 1.6) microg x mL(-1) x h(-1), (17.5 +/- 1.4) h(-1), respectively. CONCLUSION: These methods applied the study of pharmacokinetics of scutellarin. After oral the scutellarin in rats, the concentration-time course doesn't obey any compartment model. The concentration-time curve is the double peaks.

Expanding the structural diversity of Bcr-Abl inhibitors: Dibenzoylpiperazin incorporated with 1H-indazol-3-amine.

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.

Association between reduced folate carrier G80A polymorphism and methotrexate toxicity in childhood acute lymphoblastic leukemia: a meta-analysis.

Abstract Methotrexate (MTX) is a key component of chemotherapeutic regimens for childhood acute lymphoblastic leukemia (ALL), and enters the cell via active transport mediated by the reduced folate carrier (RFC1). A major single-nucleotide polymorphism of the RFC1 gene, G80A, which affects the activity of RFC1, may influence MTX toxicity in pediatric ALL. We collected all studies that investigated the association of RFC1 G80A polymorphism and MTX toxicity in pediatric ALL, and found inconsistency among their results. The aim of this meta-analysis was to summarize all of these studies in order to clarify the correlation between the RFC1 G80A polymorphism and MTX toxicity in pediatric ALL. A recessive model demonstrated no influence of the RFC1 G80A genotype on MTX toxicity. In conclusion, the RFC1 G80A polymorphism does not seem to be a good marker of MTX-related toxicity in pediatric ALL.

Recent advances in the structure-based design of neuraminidase inhibitors as antiinfluenza agents.

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.

Clinical pharmacokinetic/pharmacodynamic profile of linezolid in severely ill intensive care unit patients.

Severely ill Intensive Care Unit (ICU) patients have an increased risk of developing multiresistant Gram-positive infections, largely due to the inappropriate use of antimicrobials. In this study, the pharmacokinetic/pharmacodynamic (PK/PD) profile of linezolid, an antibiotic against Gram-positive infections, was characterised in eight critically ill patients admitted to the ICU. Remarkable variation amongst patients in the PK parameters of linezolid was observed, including a 5-7-fold difference in peak serum concentration (C(max)) (mean±standard deviation 15.70±6.58 mg/L) and 12-h area under the serum concentration-time curve (AUC(0-12)) (96.73±56.45 mg h/L), although the minimum inhibitory concentration (MIC) was similar amongst patients. In particular, variation amongst patients was found in the ratio of AUC(0-24)/MIC (range 31.66-216.82, mean 96.73) and the percentage of time that the serum concentration exceeded the MIC (T>MIC) (range 53.4-100%), two parameters used to predict linezolid efficacy. These variations highlight the importance of individual monitoring of linezolid PK/PD properties in critically ill patients. Furthermore, it was observed that regardless of AUC(0-24)/MIC and T>MIC values, the clinical and microbiological responses of patients were primarily affected by the individual's pathophysiological condition. In summary, these findings point to highly variable PK/PD properties of linezolid in severely ill patients, providing the rationale for targeting linezolid dosage to each individual patient's specific properties. An optimal dosage regimen based on individual PK/PD properties and pathophysiological conditions will help reduce the occurrence of resistance in Gram-positive bacteria.