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Apatinib, a small-molecule multitargeted tyrosine kinase inhibitor, is in phase III clinical trial for the treatment of patients with non–small-cell lung cancer and gastric cancer in China. In this study, we determined the effect of apatinib on the interaction of specific antineoplastic compounds with P-glycoprotein (ABCB1), multidrug resistance protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP, ABCG2). Our results showed that apatinib significantly enhanced the cytotoxicity of ABCB1 or ABCG2 substrate drugs in KBv200, MCF-7/adr, and HEK293/ABCB1 cells overexpressing ABCB1 and in S1-M1-80, MCF-7/FLV1000, and HEK293/ABCG2-R2 cells overexpressing ABCG2 (wild-type). In contrast, apatinib did not alter the cytotoxicity of specific substrates in the parental cells and cells overexpressing ABCC1. Apatinib significantly increased the intracellular accumulation of rhodamine 123 and doxorubicin in the multidrug resistance (MDR) cells. Furthermore, apatinib significantly inhibited the photoaffinity labeling of both ABCB1 and ABCG2 with [125I]iodoarylazidoprazosin in a concentration-dependent manner. The ATPase activity of both ABCB1 and ABCG2 was significantly increased by apatinib. However, apatinib, at a concentration that produced a reversal of MDR, did not significantly alter the ABCB1 or ABCG2 protein or mRNA expression levels or the phosphorylation of AKT and extracellular signal–regulated kinase 1/2 (ERK1/2). Importantly, apatinib significantly enhanced the effect of paclitaxel against the ABCB1-resistant KBv200 cancer cell xenografts in nude mice. In conclusion, apatinib reverses ABCB1- and ABCG2-mediated MDR by inhibiting their transport function, but not by blocking the AKT or ERK1/2 pathway or downregulating ABCB1 or ABCG2 expression. Apatinib may be useful in circumventing MDR to other conventional antineoplastic drugs. Cancer Res; 70(20); 7981–91. ©2010 AACR.

Supplementary Figure 2 from Apatinib (YN968D1) Reverses Multidrug Resistance by Inhibiting the Efflux Function of Multiple ATP-Binding Cassette Transporters

Supplementary Figure 1 from Apatinib (YN968D1) Reverses Multidrug Resistance by Inhibiting the Efflux Function of Multiple ATP-Binding Cassette Transporters

Supplementary Figure 3 from Apatinib (YN968D1) Reverses Multidrug Resistance by Inhibiting the Efflux Function of Multiple ATP-Binding Cassette Transporters

Gloeostereum incarnatum has edible and medicinal value and was first cultivated and domesticated in China. We sequenced the G. incarnatum monokaryotic strain GiC-126 on an Illumina HiSeq X Ten system and obtained a 34.52-Mb genome assembly sequence that encoded 16,895 predicted genes. We combined the GiC-126 genome with the published genome of G. incarnatum strain CCMJ2665 to construct a genetic linkage map (GiC-126 genome) that had 10 linkage groups (LGs), and the 15 assembly sequences of CCMJ2665 were integrated into 8 LGs. We identified 1912 simple sequence repeat (SSR) loci and detected 700 genes containing 768 SSRs in the genome; 65 and 100 of them were annotated with gene ontology (GO) terms and KEGG pathways, respectively. Carbohydrate-active enzymes (CAZymes) were identified in 20 fungal genomes and annotated; among them, 144 CAZymes were annotated in the GiC-126 genome. The A mating-type locus (MAT-A) of G. incarnatum was located on scaffold885 at 38.9 cM of LG1 and was flanked by two homeodomain (HD1) genes, mip and beta-fg. Fourteen segregation distortion markers were detected in the genetic linkage map, all of which were skewed toward the parent GiC-126. They formed three segregation distortion regions (SDR1–SDR3), and 22 predictive genes were found in scaffold1920 where three segregation distortion markers were located in SDR1. In this study, we corrected and updated the genomic information of G. incarnatum. Our results will provide a theoretical basis for fine gene mapping, functional gene cloning, and genetic breeding the follow-up of G. incarnatum.

In modern societies, people are more likely to be exposed to technological devices that emit extreme low frequency (ELF

The bat algorithm (BA) is a heuristic algorithm that globally optimizes by simulating the bat echolocation behavior. In order to improve the search performance and further improve the convergence speed and optimization precision of the bat algorithm, an improved algorithm based on chaotic map is introduced, and the improved bat algorithm of Levy flight search strategy and contraction factor is proposed. The optimal chaotic map operator is selected based on the simulation experiments results. Then, a multipopulation parallel bat algorithm based on the island model is proposed. Finally, the typical test functions are used to carry out the simulation experiments. The simulation results show that the proposed improved algorithm can effectively improve the convergence speed and optimization accuracy.

Purpose: To study the different effects of single- and hybrid-frequency magnetic fields on long-term potentiation (LTP) in synaptic plasticity. Materials and methods: Based on the online electromagnetic field stimulation system and field excitatory postsynaptic potentials (fEPSPs) recording system, we applied four different single- and hybrid-frequency magnetic fields with an intensity of 1 mT to the Schaffer collateral (CA1) pathway of rat hippocampal slices in vitro. Results: The amplitude of fEPSPs decreased significantly under both single- and hybrid-frequency magnetic stimulation. Lower single-frequency magnetic stimulation on LTP had a greater regulating effect, while the regulating effect among four different hybrid-frequency extremely low-frequency electromagnetic fields (ELF-EMFs) stimulations on LTP showed no significant differences. Conclusion: Single-frequency magnetic stimulation produces more significant regulatory effects, and the lower the frequency, the more significant the regulatory effect. The effect of hybrid-frequency magnetic stimulation in each group was similar, and there was no significant difference between each group. The 15-Hz single-frequency magnetic stimulation group showed the most significant regulatory effect, but once it was mixed with other higher frequency magnetic stimulation, its regulation effect was significantly weakened.

This paper presents an experimental study on total heat transfer coefficient (ht) in oscillating heat pipe heat exchanger hot air flow tunnels, ht plays an important role in the oscillating heat pipes design process. In this paper, ht and the convective heat transfer coefficient (h) was investigated by experimentally and theoretical calculation respectively. From experimental study, the relationship between the ratio of heat transfer coefficient and the relative humidity is obtained. The results show that the ratio of ht to h increases from 5 to 20 as the relative humidity of the hot gas increasing from 19.22% to 60%. According to the experimental data, a matched curve and an empirical equation were presented, which can be described as ht=h(1.87783+0.09631x+0.0032x2).

Intracranial hypotension, especially spontaneous intracranial hypotension (SIH), is a well—recognized entity associated with cerebrospinal fluid (CSF) leaks, and has being recognized better in resent years, while still woefully inadequate. An increasing number of factors including iatrogenic factors are realized to involve in development and progression of intracranial hypotension. The diagnosis remains difficult due to the various clinical manifestations, some of which are nonspecific and easily to be neglected. Multiple imaging tests are optional in CSF leakage identification while clinicians are still confronted with difficulties when making selection resulting from superiorities and disadvantages of different imaging tests. Treatments for intracranial hypotension are multifarious but evidence is anecdotal. Values of autologous epidural blood patching (EBP), the mainstay of first-line interventional treatment currently, is getting more and more regards while there are no systematic review of its efficacy and risks. Hereby, the purpose of this review was to reveal the present strategy of intracranial hypotension diagnosis and treatment by reviewing literatures, coupled with our experience in clinical work.

Sedation for the coblation-assisted upper airway procedure has lacked easy modulation between appropriate pain control and airway protection. This study aimed to compare the effectiveness of dexmedetomidine versus target controlled propofol infusion in providing sedation during a coblation-assisted upper airway procedure.In a prospective, randomized trial, 60 adult patients with obstructive sleep apnea syndrome due to undergoing a coblation-assisted upper airway procedure were enrolled and randomly allocated to receive dexmedetomidine, 1.0 µg/kg over 10 minutes and maintain dosage 0.7 µg×kg(-1)×h(-1) (n=30) or propofol target controlled infusion (n=30). Satisfaction with the analgesia and tolerance of the procedure by the patient, as assessed by a visual analogue scale, were evaluated as primary outcomes. Cardiopulmonary parameters and some side effects were monitored and recorded.Both groups of 30 patients had comparable demographics and initial parameters. Patients in the propofol group reported more pain (P0.05), tolerated the procedure less well (P0.05), and were less satisfied with the different stages of procedure (P0.05 or P0.01). Changes in mean arterial pressure and heart rate were more dramatic in the propofol group (P0.05). The dexmedetomidine group experienced fewer airway events and less respiratory depression than did the propofol group.Dexmedetomidine in conjunction with local anesthesia offered better analgesia and conscious sedation for a coblation-assisted upper airway procedure as well as less airway obstruction, apnea and greater haemodynamic stability.

Apatinib, a small-molecule multitargeted tyrosine kinase inhibitor, is in phase III clinical trial for the treatment of patients with non–small-cell lung cancer and gastric cancer in China. In this study, we determined the effect of apatinib on the interaction of specific antineoplastic compounds with P-glycoprotein (ABCB1), multidrug resistance protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP, ABCG2). Our results showed that apatinib significantly enhanced the cytotoxicity of ABCB1 or ABCG2 substrate drugs in KBv200, MCF-7/adr, and HEK293/ABCB1 cells overexpressing ABCB1 and in S1-M1-80, MCF-7/FLV1000, and HEK293/ABCG2-R2 cells overexpressing ABCG2 (wild-type). In contrast, apatinib did not alter the cytotoxicity of specific substrates in the parental cells and cells overexpressing ABCC1. Apatinib significantly increased the intracellular accumulation of rhodamine 123 and doxorubicin in the multidrug resistance (MDR) cells. Furthermore, apatinib significantly inhibited the photoaffinity labeling of both ABCB1 and ABCG2 with [125I]iodoarylazidoprazosin in a concentration-dependent manner. The ATPase activity of both ABCB1 and ABCG2 was significantly increased by apatinib. However, apatinib, at a concentration that produced a reversal of MDR, did not significantly alter the ABCB1 or ABCG2 protein or mRNA expression levels or the phosphorylation of AKT and extracellular signal–regulated kinase 1/2 (ERK1/2). Importantly, apatinib significantly enhanced the effect of paclitaxel against the ABCB1-resistant KBv200 cancer cell xenografts in nude mice. In conclusion, apatinib reverses ABCB1- and ABCG2-mediated MDR by inhibiting their transport function, but not by blocking the AKT or ERK1/2 pathway or downregulating ABCB1 or ABCG2 expression. Apatinib may be useful in circumventing MDR to other conventional antineoplastic drugs. Cancer Res; 70(20); 7981–91. ©2010 AACR.

To explore the protective effects of hydroxyethyl starch (HES)(130/0.4) against ischemia reperfusion injury of kidney and its impact on the expression of intercellular adhesion molecule-1 (ICAM-1).Forty SD rats underwent resection of the right kidney and clamping of the left renal artery for 60 min to establish renal ischemia reperfusion model, and then were randomly divided into 4 equal groups: Group S, undergoing infusion of normal saline 20 mg/kg 20 min before the reopening of the renal artery, Group W1, undergoing infusion of HES 5 mg/kg 20 min before the reopening of the renal artery, Group W2, undergoing infusion of HES 10 mg/kg, and Group W3, undergoing infusion of normal saline 20 mg/kg. Ten rats underwent sham operation and were used as controls (Group C). 24 h after reperfusion arterial blood samples were collected to detect 6 the levels of serum creatinine (Cr) and blood urea nitrogen (BUN), and then the rats were killed with their kidneys taken out to undergo pathological examination and calculation of Paller's score. Immunohistochemistry was used to detect the expression of intercellular adhesion molecule-1 (ICAM-1).The levels of BUN and Cr of Group S were 152 +/- 22 and 3.17 +/- 1.00 mmol/L respectively, both significantly higher than those of Group C, and the levels of BUN and Cr of Groups W2 and W3 were 99 +/- 23 and 1.82 +/- 0.86 mmol/L and 92 +/- 28 and 1.57 +/- 0.70 mmol/L respectively, all significantly lower than those of Group S (P0. 05 or P0.01). The Paller's scores of W2 and W3 were 33.6 +/- 16.6 and 29.2 +/- 12.3 respectively,both significantly lower that of Group S (43.2 +/- 15. 8, both P0.05). The absorption levels of ICAM-1 of Groups W2 and W3 were 182 +/- 22 and 161 +/- 25 respectively, both significantly lower than that of Group S (212 +/- 32, P0.01).Infusion of 10-20 ml/kg HES (130/0.4) significantly alleviates the ischemia-reperfusion injury, probably by reducing the ICAM-1 expression.

To evaluate the clinical usefulness of impedance pneumography in determining the tube placement during endotracheal intubation.Thirty-six endotracheally-intubated patients for elective operations underwent general anesthesia and endotracheal intubation, and then a second identical tube was inserted into the esophagus under laryngoscopic control. The ventilation circuit was then attached either to tracheal or esophageal tube. The tube position was determined by 2 blinded examiners, one experienced and the other inexperienced, using three methods: impedance pneumography, capnography, and auscultation. The order of the tubes tested and the order of the methods used were randomized. The observation results and the time needed to determine were recorded by another assistant.Of the 216 tests conducted, both examiners correctly diagnosed the position of the tube using impedance pneumography and capnography. In the auscultation method there were two false-negative results (with the tracheal tube identified as esophageal) and one false-positive (with the esophageal tube identified as tracheal) by the experienced examiner, while five false-negative results (with the tracheal tube identified as esophageal) and nine false-positive (with the esophageal tube identified as tracheal) by the inexperienced examiner. With the sensitivity and specificity of impedance pneumography as standards (100%), the sensitivity and specificity of the capnography were both 100% too, and the sensitivity and specificity of the auscultation method were 90% and 86% respectively, both significantly lower than those of the other 2 methods (all P0.01). Capnography needed 3.4 s+/-1.3 s and 3.7 s+/-1.4 s to verify tracheal intubation and esophageal intubation respectively, both significantly longer than those of the auscultation methods (1.7 s+/-0.7 s and 2.5 s+/-1.7 s) and impedance pneumography (1.6+/-0.3 and 2.1+/-1.1s, all P0.01). It took less time for impedance pneumography and auscultation to verify the tracheal intubation than to verify esophageal intubation (both P0.01).Impedance pneumography is one of the reliable methods for diagnosing tracheal tube position.