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During the movement of Typhoon Hato (2017) over land, heavy rainfall occurred when the spiral rainband which was about 100 km distance away from the center of the typhoon passed the Dayao Mountain (with an elevation of 1.2 km). In this study, the structures and forming mechanism of the heavy rainband along the mountain range are investigated by using high-resolution model simulations. The results show the importance of topography in causing the heavy rainband. Upslope of the steep terrain lifts the cyclonic flow to produce strong upward motion when the rainband passes across with high wind speed. At the same time, the warm and humid air is lifted to the steep slope, causing unstable energy to accumulate over the windward slope, which is conducive to the occurrence of rainfall. In particular, the convective cells generated upstream of rainband will further strengthen and develop due to the uplift when they move close to the mountain foot. Some precipitation particles in the convective cells fall to the ground while others move downstream with the intense updrafts, forming heavy rainfall near the summit. As a result, the largest accumulative rainfall coincides well with the orientation of the mountain ridge. [ABSTRACT FROM AUTHOR]

In this study, fine structures of spiral rainbands in super Typhoon Chanchu(2006) are examined using an Advanced Research Weather Research and Forecast(WRF-ARW) model simulation with the finest grid size of 2 km.Results show that the simulation reproduces well Typhoon Chanchu's track, intensity and basic structures. According to their locations and features, spiral rainbands are classified into principal, secondary, inner and distant rainbands, and their dynamic and thermodynamic features are investigated. The principal rainbands remain quasi-stationary with respect to Chanchu's center and exhibit a wavenumber-1 feature with their outer edges separated by dry air. The secondary rainbands that occur on the radially inward side of the principal rainbands move around Chanchu's center. The inner rainbands are closest to the center. They propagate both radially outward and azimuthally with time. The distant rainbands are located outside the inner-core region, and have stronger and continuous updrafts compared to the other rainbands. Distant rainbands are inward-sloping with height along the radial direction and have a cold pool in the low layers, whereas the principal and secondary rainbands lean radially outward with height. The inner rainbands do not show tilting with height along the radial direction. However, there are few vertical tilting cells along the azimuthal orientation among the four types of rainbands. The simulated radar reflectivity cores in all rainbands are collocated with the maxima of updrafts and equivalent potential temperatures in the low layer, indicating the important roles of energy supply in the boundary layer in determining the development of the rainband convection. [ABSTRACT FROM AUTHOR]

Point cloud data extraction is an important process in scan-tracking measurement. In this paper, a new method of on-line three-dimensional point cloud data extraction for scan-tracking measurement is proposed for reducing extremely dense sampled data while maintaining data accuracy during the real-time scan-tracking measuring process. It is inspired from sketch paintings: First outlining the broad contour of the curve and then revising local details till the interpolated curve satisfies the required accuracy. This method adopts bi-Akima spline interpolation for connecting acquired points in NC machining or for point data fitting in reverse engineering. It can reduce efficiently the amount of point data with a smaller data reduction ratio and a smoother machined/fitted surface than conventional three-dimensional chordal method. [ABSTRACT FROM AUTHOR]

This paper proposes a complete real-time Ethernet (RTE) solution including master and slave controllers for numerical control (NC) systems. To meet the development tendency of NC systems moving toward multi-axis coordination, high speed and high precision, one type of RTE architecture is built up with a dual ring topology. The function blocks of master/slave nodes are designed to realize the real-time communication capabilities using embedded CPU and field programmable gate array (FPGA) technologies. To reduce the minimum achievable cycle time, a cut-through transmission mechanism is employed to decrease the process latency at slave nodes, and the synchronization frame is optimized to shorten the frame duration. In order to synchronize the nodes of RTE-based NC systems accurately, a time synchronization strategy is scheduled and a proportion-integration (PI)-based phase-locked loop (PLL) is designed to keep the master clock and the slave clocks in step stably. The theoretical analysis and experimental results show that the proposed RTE solution can achieve good real-time performance with low process latency and high time-synchronization accuracy, which satisfies the real-time communication requirements of RTE-based NC systems in an economical way. [ABSTRACT FROM AUTHOR]

Abstract: This paper proposes an advanced M/T method called Relay-style Digital Speed Measurement Method. Its speed measurement is triggered by encoder pulse signals, which simplifies the complexity of processing incapability of synchronization in the classical method, and it makes actual sampling point always occur before the periodic sampling point in relay-style, which achieves the continuous dynamic iterative measurement with high accuracy in a wide speed range. Through counting the overflow pulses of time counter by software, the minimally measurable speed can be effectively extended to an extremely low level without adding any hardware. In addition, by utilizing the information in speed measurement and subdividing dynamic position by time according to its corresponding relationship with time, Dynamic Position Subdivision Method is achieved to improve the feedback resolution of dynamic position. Finally, the experimental results show that Relay-style Digital Speed Measurement Method can obtain high accuracy than classical method in a wide speed range even though at a very low speed Dynamic Position Subdivision Method is helpful to reduce the fluctuations of the position control. [Copyright &y& Elsevier]

Surface scan-tracking measurement is one of the key technologies in copying manufacture. In conventional scan-tracking measuring processes of irregular surface, the model surface geometric shape and the friction between the probe and model surface are two main factors that can seriously affect the measuring accuracy and efficiency. In order to reduce the impact of these factors and improve measurement efficiency while maintaining measurement accuracy, this paper presents a novel embedded cerebellar modular articulation controller (CMAC) learning controller for scan-tracking measurement in copying manufacture. New approaches to model surface features (including geometric feature and friction feature) identification and quantification are given specifically. Conventional scan-tracking control law is improved by taking into account the impact of model surface feature, and it is combined with CMAC neural network so that it can automatically predict the surface features and adjust the scan-tracking velocity in advance. Thus, high measuring efficiency can be obtained by accelerating scan speed in smooth areas of model surface and decelerating prior to scanning the surface feature cusp regions. Working with a commercial open CNC system, the design steps, integration process, and results of applying the embedded CMAC learning controller were described in detail through the examples of real measurement. Actual industrial tests show a higher measurement efficiency which demonstrates the effectiveness of proposed control strategy for scan-tracking measurement. [ABSTRACT FROM AUTHOR]

Point cloud data acquisition is the first key step in digital copying manufacture. In order to reduce extremely dense acquired data while maintaining data accuracy, this paper presents a simple and practical on-line point cloud data reduction method for digital copying manufacture, which is based on Akima spline interpolation. The basic idea of this method is similar to sketch painting: Outline the broad contour of the curve first and then revise local details until the interpolated curve satisfies the required accuracy. In this method, Akima spline interpolation is adopted to connect acquired points for CNC machining in digital copying process. It obtains a smaller data reduction ratio and a smoother machined surface than conventional methods. Experimental results indicate that the proposed Akima reduction method is able to eliminate redundant data effectively under different required accuracy. The reduction performance of this method is superior to equal ATCD reduction method obviously under the same required accuracy. The proposed method can be used in the real-time data acquisition process of digital copying manufacture to replace traditional methods. [ABSTRACT FROM AUTHOR]

Head-of-line (HOL) blocking limits the throughput of high radix switches. An efficient architecture, OE-ASC, is proposed for high-radix switches. This architecture takes advantages of two cost-effective strategies for dealing with the HOL blocking problem. The first is referred to as asymmetric crossbar/ASC), through which a NXN switch can be formed by N/m smaller mXN asymmetric crossbars, and the second is odd-even queues scheme, through which the resources (mainly memory queues) of the switch can be used more efficiently. A tile-based microarchitecture of 32×32 high radix switch is proposed. Clock cycl-accurate simulation shows that the impact of HOL blocking is nearly all eliminated and the switch throughput can be as high as 98. 6%. The proposed OE-ASC architecture shows up to 7. 9% of throughput over ASC with buffer depth 16, and can achieve comparable performance with half buffers. [ABSTRACT FROM AUTHOR]

Abstract: This paper is concerned with the optimal design of motion control for scan tracking measurement using Cerebellar Model Articulation Controller (CMAC) neural networks in order to improve the measuring efficiency while maintaining the measurement accuracy, and to achieve friction compensation. Aiming at the effect of geometric shape and material friction of the model surface on the precision and efficiency of scan tracking measurement, technologies of model surface geometric and friction feature identification and quantification are researched. A novel optimal motion controller for scan tracking measurement is designed and realized, which automatically predicts the surface features (including geometric feature and friction feature) and adjusts the scan tracking velocity in advance. The approach to friction quantification and compensation in measuring process is given specifically. Finally, through Matlab simulation experiments, the realizability and application effect of the studied optimal motion control method for scan tracking measurement are verified, and the measuring efficiency is increased by 123.33%. Simulation results show that the proposed motion controller is an effective way to enhance the measurement efficiency remarkably compared with the traditional control strategy. [Copyright &y& Elsevier]

Presents a case study of a woman with congenital double-chambered right ventricle and ventricular septal defect, complicated by subacute bacterial endocarditis. Diagnosis and treatment; Discussion on the case.

Objective: To evaluate and present the effectiveness of this innovatively designed, elastic locking intramedullary nail (ELIN) in fixation of clavicle fractures. Methods: The study included 38 patients from July 2014 to July 2017. All of them received intramedullary fixation treated with ELIN, 22 were males and 16 females. The mean age of the patients was 54 years. There were twenty right‐side and 18 left‐side clavicular fractures. Radiographs were taken to assess the fracture type: 21 were type A, 16 type B, and one type C. General anesthesia or cervical block was given to all patients. A small incision of 3–5 cm was given only to those who needed mini‐open reduction. The administration of ELIN and reduction of the fracture was made sure with a C arm machine. After a follow‐up of 8 to 33 months, the clinical outcomes were assessed and evaluated. The constant scores and disabilities of the arm, shoulder and hand questionnaire (DASH) were used to determine the outcomes and functional status of the patients. The study was done accordingly to the guidelines provided by the ethics committee. Results: Mean operation time was 25.63 min. Mean follow‐up time was 16.5 months. The rate of closed reduction and open reduction was 84% and 16% respectively. There was no shortening of the clavicle. There was no breakage of the nail, though bending of the nail occurred in one patient. Superficial skin infection occurred in three patients at insertion points or the nail tip which was embedded subcutaneously. Skin erosion with nail exposure occurred in a patient with no significant infection. All the other patients had excellent shoulder function. A mini scar was observed in seven patients all the other patients had no scar. Asymmetry was observed in three patients. The mean Constant score was 98.47 and the mean DASH score was 1.55 at the last follow‐up. The implant was removed in all the patients. Conclusion: Clavicular fractures treated with ELIN is minimally invasive, which presents a safe and novel surgical technique with less complications and a high success rate, excellent aesthetic and quick recovery after surgery. ELIN restores the micro‐dynamic stress at the fracture ends and promotes fracture healing, keeps intact the fracture hematoma and maintains the blood supply, accelerates healing and thus leads to faster osseous healing and better restoration of clavicle length. [ABSTRACT FROM AUTHOR]

• We present an efficient closed-form representation of molar Gibbs free energy for gaseous substances. • Present molar Gibbs free energy calculation model only involves three molecular constants. • We excellently predict molar Gibbs free energy values for the gases Cl 2 , Br 2 , and HCl. We develop a new closed-form representation for the molar Gibbs free energies of gaseous substances. The predicted molar Gibbs free energies are in excellent agreement with the experimental data in a wide temperature range for three gases under consideration, and the average absolute deviations of the predicted results from the experimental data are 0.06155%, 0.0708% and 0.16696% for the gases Cl 2 , Br 2 , and HCl, respectively. The proposed model is away from the need of a large amount of experimental spectroscopy data, and only related to the dissociation energy, equilibrium bond length, and equilibrium vibration frequency. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • We present an efficient closed-form representation of molar enthalpy for gaseous substances. • Present molar enthalpy calculation model only involves four molecular constants. • We excellently predict molar enthalpy values for the CO, HCl, and BF gases. Abstract We present a universal efficient closed-form representation for the molar enthalpy of gaseous substances. The predicted molar enthalpy values show excellent agreements compared to the experimental data in a wide temperature range for the gases CO, HCl, and BF. The proposed model is away from the need of plenty of experimental spectroscopy data, and depends on only four molecular constants, for which the experimental values can be easily found in the literature. [ABSTRACT FROM AUTHOR]

Ibrutinib, orelabrutinib, and zanubrutinib are all Bruton's tyrosine kinase inhibitors, which have greatly improved the treatment of B-cell malignancies. In this study, an LC-MS/MS method was developed and validated for the determination of orelabrutinib, zanubrutinib, ibrutinib, and its active metabolite dihydrodiol ibrutinib in human plasma. The Ibrutinib-d5 was used as the internal standard. Pretreatment was performed using a simple protein precipitation step using acetonitrile. The ACQUITY UPLC HSS T3 column (2.1×50 mm, 1.8 μm) was used to separate the analytes, and the run time was 6.5 min. The mobile phase consisted of acetonitrile and 10 mM of ammonium formate, which contained 0.1% formic acid. The multiple reactions' monitoring transitions were selected at m/z 428.1→411.2, 472.2→455.2, 441.1→304.2, 475.2→304.2 and 446.2→309.2 respectively for orelabrutinib, zanubrutinib, ibrutinib, dihydrodiol ibrutinib and ibrutinib-d5 using positive ion electrospray ionization. The standard curves were linear, from 0.400 to 200 ng/mL for ibrutinib and dihydrodiol ibrutinib, 1.00–500 ng/mL for orelabrutinib, and 2.00–1000 ng/mL for zanubrutinib. Selectivity, the lower limit of quantitation, precision, accuracy, matrix effect, recovery, stability, and dilution integrity all met the acceptance criteria of FDA guidance. This method was used to quantify the plasma levels of orelabrutinib, zanubrutinib, ibrutinib, and dihydrodiol ibrutinib in clinical patients. [ABSTRACT FROM AUTHOR]

The feasibility of taking the ratio of 6β-hydroxycortisol (6β-OHCOR) to cortisol (COR) in plasma as a biomarker to reflect CYP3A4 activity needs to be verified, but the low concentration of 6β-OHCOR which is an endogenous substance in plasma presents a challenge for determination. In this study, a Liquid chromatography with tandem mass spectrometry (LC–MS/MS) method was established to simultaneously quantify the COR and 6β-OHCOR in plasma with COR-d4 and 6β-OHCOR-d4 as internal standards (ISs). Plasma samples were treated by protein precipitation using acetonitrile. Separation with a gradient elution within 5 min was achieved on C18+ column utilizing 5 mM ammonium formate and methanol. An API 4,000 MS in multiple reaction monitoring mode with transitions of 407.1 → 361.1 and 423.1 → 347.1 was utilized. Albumin solution was used as a surrogate matrix, with good linearities over the concentration of 1.20–300 ng/mL for COR and 0.0400–10.0 ng/mL for 6β-OHCOR. The precisions for intrarun and interrun were < 6.8%, and the accuracy was fell in the interval of −5.2 to 3.5%. Matrix effect was not found. Recovery was close to 100.0%. Stability was confirmed under the storage and processing conditions. The validated method was applied to evaluate the inhibitory effect of voriconazole to CYP3A by the ratio of 6β-OHCOR to COR. [ABSTRACT FROM AUTHOR]

The human HtrA family of serine proteases (HtrA1, HtrA2, HtrA3, and HtrA4) are the key enzymes associated with pregnancy and closely related to the development and progression of many pathological events. Previously, it was found that halogen substitution at the indole moiety of peptide Trp-1 residue can form a geometrically satisfactory halogen bond with the Drosophila discs large, zona occludens-1 (PDZ) domain of HtrA proteases. Here, we attempt to systematically investigate the effect of substitution with 4 halogen types and 2 indole positions on the binding affinity and specificity of peptide ligands to the 4 HtrA PDZ domains. The complex structures, interaction energies, halogen-bonding strength, and binding affinity of domain-peptide systems were modeled, analyzed, and measured via computational modeling and fluorescence-based assay. It is revealed that there is a compromise between the local rearrangement of halogen bond involving different halogen atoms and the global optimization of domain-peptide interaction; the substitution position is fundamentally important for peptide-binding affinity, while the halogen type can effectively shift peptide selectivity between the 4 domains. The HtrA1-PDZ and HtrA4-PDZ as well as HtrA2-PDZ and HtrA3-PDZ respond similarly to different halogen substitutions of peptide; -Br substitution at R2-position and --I substitution at R4-position are most effective in improving peptide selectivity for HtrA1-PDZ/HtrA4-PDZ and HtrA2-PDZ/HtrA3- PDZ, respectively; -F substitution would not address substantial effect on peptide selectivity for all the 4 domains. Consequently, the binding affinities of a native peptide ligand DSRIWWV--COOH as well as its 4 R2-halogenated counterparts were determined as 1.9, 1.4, 0.5, 0.27, and 0.92 µM, which are basically consistent with computational analysis. This study would help to rationally design selective peptide inhibitors of HtrA family members by using different halogen substitutions. [ABSTRACT FROM AUTHOR]

For obtaining high-quality point cloud data of a measured surface in copying manufacture, 3D scanning devices typically have extremely high data sampling rate to produce huge amounts of dense points, which lead to significant computational challenges for subsequent data processing tasks in practical applications. Bottlenecks are created owing to inefficiencies in storing, manipulating, and transferring the massive point data. On-line point cloud data extraction is an effective means to solve the above problems. This paper proposes a novel on-line point cloud data extraction algorithm for spatial scanning measurement of irregular surface. The proposed data extraction framework can handle point sets of arbitrary and varying size, point density, and scanning line shape. Furthermore, it can reduce extremely dense point cloud data in ensuring data accuracy during the real-time scanning measuring process. Additionally, we present a bi-Akima method for connecting spatial point sequence in non-planar cross section. It is designed to deal with point cloud data extraction for any kinds of scanning lines during the real-time measuring process. Finally, a series of simulations and real measuring experiments are conducted, and the results show a strong data extraction performance of our proposed method both in data reduction ratio and accuracy. [ABSTRACT FROM AUTHOR]

A convenient and sensitive liquid chromatography–tandem mass spectrometry method was established to simultaneously quantify voriconazole (VRZ) and its metabolite, voriconazole N -oxide (VNO), in human urine. Voriconazole-d3 and voriconazole-d3 N -oxide were used as isotopic internal standards. Samples were processed by protein precipitation and separated using a ZORBAX SB-Aq column (1.8 μm, 2.1 × 50 mm). Mass spectrometry was performed using an API 4000 mass spectrometry by positive electrospray ionization. The flow rate was 0.6 mL/min. Gradient elution was performed with methanol and 0.1% formic acid as the organic and water phase, respectively. The VRZ and VNO calibration curves ranged from 20.0 to 7200 ng/mL in human urine. The specificity, matrix effect, extraction recovery, intra/inter-run precision, accuracy and stability were validated for both VRZ and VNO in human urine. The developed method was used to study urinary excretion after intravenous injection of 4 mg/kg VRZ in healthy Chinese subjects. [ABSTRACT FROM AUTHOR]

[Display omitted] Calcium (Ca2+) acts as a second messenger and constitutes a complex and large information exchange system between the endoplasmic reticulum (ER) and mitochondria; this process is involved in various life activities, such as energy metabolism, cell proliferation and apoptosis. Increasing evidence has suggested that alterations in Ca2+ crosstalk between the ER and mitochondria, including alterations in ER and mitochondrial Ca2+ channels and related Ca2+ regulatory proteins, such as sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), inositol 1,4,5-trisphosphate receptor (IP3R), and calnexin (CNX), are closely associated with the development of kidney disease. Therapies targeting intracellular Ca2+ signaling have emerged as an emerging field in the treatment of renal diseases. In this review, we focused on recent advances in Ca2+ signaling, ER and mitochondrial Ca2+ monitoring methods and Ca2+ homeostasis in the development of renal diseases and sought to identify new targets and insights for the treatment of renal diseases by targeting Ca2+ channels or related Ca2+ regulatory proteins. [ABSTRACT FROM AUTHOR]

A three-dimensional (3-D) multi-functional mixed valence CuII/CuI-MOF, {[Cu(CuI)2(2-pyzc)2H2O]2·H2O}n (Hpyzc = pyrazine-2-carboxylic acid), has been solvothermally synthesized and successfully characterized by FT-IR spectroscopy, elemental analysis, powder X-ray diffraction, thermal gravimetric analysis (TGA) and single-crystal X-ray diffraction. The structure posesses a 3-D open framework containing 1-D channels and shows a tcj topological network with the Schläfli symbol (43·612)(43)2. This MOF exhibits selective adsorption of CO2/H2 over CH4/N2 and excellent catalytic activity in the oxidation of benzylic compounds and three-component coupling reactions of aromatic alkynes, tosyl azide and diisopropylamine as a cooperative catalyst. The catalyst could be reused several times without significant degradation in catalytic activity. [ABSTRACT FROM AUTHOR]

Pivmecillinam, the ester of biologically active antibiotic mecillinam, is an effective oral preparation to treat urinary tract infections. To study pharmacokinetics in humans, LC‐MS/MS methods were developed to quantify pivmecillinam and mecillinam in human plasma, respectively. Considering cephalexin as internal standard, analytes were separated on UltimateXB‐C18 columns after protein precipitation by acetonitrile. The mobile phase was composed of water containing 0.1% formic acid and methanol. The multiple reactions monitoring transitions of m/z 440.2→167.1, 326.1→167.1, and 348.1→158.1 were selected to inspect pivmecillinam, mecillinam, and the internal standard in positive ion mode. No apparent matrix effect was perceived. Linearities were obtained over calibration ranges of 0.0500–12.0 and 10.0–15,000 ng/mL, respectively. The intraday precisions were below 5.5%, the interday precisions were below 6.1%, and accuracies were within –8.1 to 13.0%. Stability tests were conducted and an acidification step was explored to enhance the stability of pivmecillinam and mecillinam. Further stability was validated under various storage and processing conditions. Both methods were applied to a pharmacokinetic study of pivmecillinam and mecillinam after oral administration of 400 mg pivmecillinam hydrochloride tablets in healthy Chinese subjects. [ABSTRACT FROM AUTHOR]

The specific inflow distribution along the horizontal wellbore is significantly uneven in highly heterogeneous reservoirs. Such uneven influx is recognized as the cause of early water breakthrough, poor oil sweep efficiency and low ultimate recovery. Interval control valves (ICVs) are practical completion hardwares that can actively equalize the contributions from all controlled zones. However, the wellhead penetration limitation impedes ICVs' application in highly heterogeneous reservoirs, which require many control intervals. This paper proposes a new completion methodology that combines ICVs and variable-density perforations (ICVs + VDP) to eliminate the limitation of ICVs applied in highly heterogeneous reservoirs. The ICVs + VDP completion can achieve more subtle controls because VDP is capable of reducing the inflow difference in each subzone. A steady-state modeling approach and a transient-state modeling approach are used to evaluate the effect of the ICVs + VDP completion on inflow equalization and well performance optimization. The observations from case study show that horizontal wells with the ICVs + VDP completion can considerably delay water breakthrough, improve oil recovery, and reduce water production in highly heterogeneous reservoirs. [ABSTRACT FROM AUTHOR]

Imatinib (IM), a milestone drug used in the field of molecular targeted therapy, has been reported to cause serious adverse liver effects, including liver failure and even death. Immune-mediated injury and mitochondrial dysfunction are involved in drug-induced liver injury. However, the mechanism of IM-induced hepatotoxicity remains unclear and warrants further study. In our study, Sprague Dawley rats were administered IM by gavage with 50 mg/kg body weight (BW) once daily for 10 days. Drug-induced liver injury accompanied by inflammatory infiltration was observed in rats following IM exposure, and the expression of NOD-like receptor protein 3 (NLRP3) inflammasome-related proteins was significantly increased compared with that of the control. HepG2 cells were exposed to 0–100 μM IM for 24 h. The results showed that IM decreased cell viability in a dose-dependent manner. Moreover, IM induced a state of obvious oxidative stress and activation of nuclear factor kappa B (NF-κB) in cells, which resulted in the activation of NLRP3 inflammasomes, including caspase 1 cleavage and IL-1β release. These results were significantly reduced after the use of the antioxidants N-acetyl-l-cysteine or the NF-κB inhibitor pyrrolidine di-thio-carbamate. Furthermore, NLRP3 knockdown significantly reduced the release of inflammatory cytokines and improved cell viability. In summary, our data demonstrated that oxidative stress and NLRP3 inflammasome activation are involved in the process of IM-induced hepatotoxicity. The results of this study provide a reference for the prevention and treatment of IM-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Regadenoson, the first selective adenosine A2A receptor agonist, is used to perform exercise stress test during radionuclide myocardial perfusion imaging. To detect the concentration of regadenoson in human plasma, a simple, fast, and sensitive tandem mass spectrometry method was established herein. Acetonitrile was used as a protein precipitation agent. Chromatographic separation was completed in 6.5 min using a BEH HILIC column (50 × 2.1 mm, 1.7 μm). The mobile phase consisted of 10 mmol/L ammonium acetate/acetonitrile (gradient elution). To quantify regadenoson and regadenoson‐d3, an API 4000 mass spectrometry in multiple reaction monitoring mode with transitions of 391.3→259.2 and 394.3→262.2, respectively, was utilized. The calibration curve was linear in the range of 0.100–50.0 μg/L, and the intrabatch and interbatch precisions were <9.7% and <13.0%, respectively, and the accuracy was 2.0–6.9%. There was no apparent matrix effect for regadenoson or regadenoson‐d3. The developed method was used to study the pharmacokinetic characteristics of regadenoson in healthy Chinese subjects. [ABSTRACT FROM AUTHOR]

Amitostigma hemipilioides is an endangered terrestrial orchid endemic to China. In the Southwestern China, the species is found restricted growing in the karst limestone or rock in the edge of farmland, moist hillsides or river. In the present study, the genetic diversity and differentiation was estimated within and among habitats, populations and groups of this species by ISSR markers. Using 13 polymorphic primers, an intermediate level of genetic diversity was found at the species level and population level with the percentage of polymorphic bands ( P) of 64.7 and 50.9 %, Shannon index of diversity ( I) of 0.3873 and 0.2949, respectively. The analysis of molecular variance (AMOVA) showed that the high level of population differentiation was presented with 45.63 % relative to the total genetic variation residing among eight populations. It was noteworthy that as much as 69.17 % of the total diversity was most likely attributed to the difference among the populations in fragmentation habitat conditions, while 16.32 % of the total diversity could be attributed to the difference among the populations in stable and favorable habitat conditions. The in situ conservation is a top strategy, thus the mycorrhizal fungi and pollinators are protected by protecting habitat and avoiding fragmentation which is helpful to the cycle of this endangered orchid species and recovery of its wild populations. In addition, to maintaining the germplasm bank of this species, the ex situ conservation by habitat simulation and reintroduction has been considered in the living collection at Kaili University ecological garden and Yuntai Mountain scenic spot using the plants collected in this study. [ABSTRACT FROM AUTHOR]

Voriconazole (VRC) is a first-line drug for the treatment of invasive fungal infections (IFIs) and an inhibitor of CYP3A activity. The aims of this study are to investigate the influence of related factors on the plasma concentration of voriconazole and the effect of voriconazole on the activity of CYP3A in patients with haematological malignancies. A total of 89 patients received an initial dose of 6 mg/kg followed by 4 mg/kg every 12 h were included in the study. Blood samples were collected before and 2 h after administration for subsequent testing and for the extraction of DNA samples. Voriconazole and voriconazole N-oxide in the plasma were detected by LC-MS/MS. The effect of voriconazole on CYP3A activity was evaluated by the ratio of the endogenous biomarkers 6β-hydroxycortisol and cortisol. During the study period, the overall incidence of adverse reactions was 33.6% (with no deaths). The metabolite type of CYP2C19 and combined use of CYP2C19 enzyme inhibitors both had a significant impact on voriconazole exposure. Voriconazole has a long-lasting and potent inhibitory effect on CYP3A activity. The exposure of CYP3A substrate in combination with metabolic enzyme inhibitors voriconazole could increase. Therefore, the combination uses with voriconazole need to be considered carefully and assessed adequately. [ABSTRACT FROM AUTHOR]

Sitafloxacin, a new fluoroquinolone, has strong antibacterial activity. We evaluated the effects of sitafloxacin granules in single‐dose and multidose cohorts and the effects of ABCB1, UGT1A1, and UGT1A9 genetic polymorphisms on the pharmacokinetics (PK) of sitafloxacin in healthy subjects. The single‐dose study included 3 fasted cohorts receiving 50, 100, and 200 mg of sitafloxacin granules and 1 cohort receiving 50 mg of sitafloxacin granules with a high‐fat meal. The multidose study included 1 cohort receiving 100 mg of sitafloxacin granules once daily for 5 days. PK parameters were calculated using noncompartmental parameters based on concentration‐time data. The genotypes for ABCB1, UGT1A1, and UGT1A9 single‐nucleotide polymorphisms were determined using Sanger sequencing. Subsequently, the association between sitafloxacin PK parameters and target single‐nucleotide polymorphisms was analyzed. Sitafloxacin granules were well tolerated up to 200 and 100 mg in the single‐dose and multidose studies, respectively. Sitafloxacin AUC and Cmax increased linearly within the detection range, and a steady state was reached within 3 days after the administration of multiple oral doses. Our findings showed that Cmax was lower in the ABCB1 (rs1045642) mutation group, whereas t1/2 was longer in the UGT1A1 (rs2741049) and UGT1A9 (rs3832043) mutation groups. In conclusion, sitafloxacin granules were safe at single doses and multiple doses up to 200 and 100 mg/day, respectively, with a linear plasma PK profile. However, ABCB1 (rs1045642), UGT1A1 (rs2741049), and UGT1A9 (rs3832043) genetic polymorphisms are likely to influence the Cmax or t1/2 and thereby merit further clinical evaluation. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors, including omeprazole, rabeprazole, lansoprazole, and pantoprazole, achieved simultaneous enantioselective determination in the human plasma by chiral liquid chromatography–tandem mass spectrometry. The four corresponding stable isotope‐labeled proton pump inhibitors were adopted as the internal standards. Each enantiomer and the internal standards were extracted with acetonitrile containing 0.1% ammonia, then separated with a Chiralpak IC column (5 µm, 4.6 mm × 150 mm) within 10 min. The mobile phase was composed of acetonitrile–ammonium acetate (10 mM) containing 0.2% acetic acid (50:50, v/v). To quantify all enantiomers, an API 4000 tandem mass spectrometer was used, and multiple reaction monitoring transitions were performed on m/z 360.1→242.1, 384.1→200.1, 370.1→252.1, and 346.1→198.1, respectively. No significant matrix effect was observed for all analytes. The calibration curve for all enantiomers were linear from 1.25 to 2500 ng/mL. The precisions for intra‐ and inter‐run were < 14.2%, and the accuracy fell in the interval of –5.3 to 8.1%. Stability of samples was confirmed under the storage and processing conditions. The developed method was also suitable for separation and determination of ilaprazole enantiomers. The validated method combining the equilibrium dialysis method was applied to the protein binding ratio studies of four pairs proton pump inhibitor enantiomers in human plasma. [ABSTRACT FROM AUTHOR]

Carotenoids are the principal pigments in the loquat. Although the metabolic pathway of plant carotenoids has been extensively investigated, few studies have been explored the regulatory mechanisms of loquat carotenoids because knowledge of the loquat genome is incomplete. The chromoplast-specific lycopene β-cyclase gene (CYC-B) could catalyze cyclization of lycopene to β-carotene. In this study, the differential accumulation patterns of loquat with different colors were analyzed and virus-induced gene silencing (VIGS) was utilized in order to verify CYC-B gene function. Using a cloning strategy of homologous genes, a CYC-B gene orthologue was successfully identified from the loquat. At a later stage of maturation, CYC-B gene expression and carotenoids concentrations in the 'Dawuxing' variety were higher than in 'Chuannong 1-5-9′, possibly leading to the difference in pulp coloration of loquat. Interference of CYC-B gene expression in the loquat demonstrated clear visual changes. The green color in negative control fruits became yellow, while TRV2-CYC-B silenced fruits remained green. CYC-B gene expression and total carotenoid content in the pulp decreased by 32.5% and 44.1%, respectively. Furthermore, multiple key genes in the carotenoid metabolic pathway synergistically responded to downregulation of CYC-B gene expression. In summary, we provide direct evidences that CYC-B gene is involved in carotenoid accumulation and coloration in the loquat. [ABSTRACT FROM AUTHOR]

Abstract (+)-Borneol, a bicyclic monoterpene, has been shown to possess valuable biological properties and potential as a pharmaceutical agent due to anti-inflammatory, anti-oxidant and GABA receptor-enhancing functions; it also enhances the permeability of the blood brain barrier to improve the efficacy of CNS drugs. In this study, we have developed a simple, selective, and rapid liquid chromatography-tandem mass spectrometry method for the assay of (+)-borneol in rat plasma. Verapamil was used as an internal standard. Plasma samples were deproteinized using methanol. The analyte was detected by a mass spectrometer with positive atmospheric pressure chemical ionization by multiple reaction monitoring mode for transitions at m / z [M + H]+ 137.2 → 81.0 for (+)-borneol and 455.2 → 165.1 for verapamil. The method has been fully validated to ensure good selectivity, a satisfactory lower limit of quantification at 10.0 ng/mL, acceptable intra- and inter-day accuracy, and high precision. The method was used for the pharmacokinetic evaluation of (+)-borneol in Sprague-Dawley rats after intravenous, oral, and sublingual administration. The results indicate that oral bioavailability of (+)-borneol was extremely low but sublingual administration yielded rapid absorption and favorable bioavailability of (+)-borneol. Graphical abstract Unlabelled Image Highlights • A simple, selective, and rapid LC-MS/MS method was validated for quantify (+)-borneol in rat plasma. • The sensitive, robust and high throughput method has been sucessfully applied for a pharmacokinetic study. • The pharmacokinetic profile of (+)-borneol as a stereoisomer was first reported. [ABSTRACT FROM AUTHOR]

Rabeprazole is an effective proton pump inhibitor to treat acid‐related diseases. To achieve the simultaneous determination of rabeprazole enantiomers in human plasma, a chiral LC‐MS/MS method was developed and validated. Acetonitrile including 0.1% ammonium were used as protein precipitating agent. Analytes were separated within 8 minutes on a Chiralpak IC column (4.6 mm × 150 mm, 5 μm). The mobile phase was 10 mM ammonium acetate including 0.2% acetic acid‐acetonitrile (35:65, v/v). An API 4000 mass spectrometer was used as detector for the analysis, and the multiple reactions monitoring transitions of m/z 360.1 → 242.2 and 346.1 → 198.1 were opted for quantifying rabeprazole enantiomers and internal standard. Matrix effects were not apparent for each enantiomer and internal standard (esomeprazole), the calibration curves were linear over the concentration of 0.500 to 400 ng·mL−1, the intra‐run precisions were below 5.4%, the inter‐run precisions were below 9.9%, and the accuracy was between −9.2% and 9.3%. There was no chiral inversion observed during sample storage, preparation procedure, and analysis, demonstrating that analytes were stable in this study. This method was applied to the stereoselective pharmacokinetic study of (R)‐(+)‐ and (S)‐(−)‐rabeprazole after oral administration of 10‐mg rabeprazole sodium enteric‐coated tablet in healthy Chinese subjects. [ABSTRACT FROM AUTHOR]

Objective: Angle stable interlocking intramedullary nail (ASIN), a novel technique, has rarely been used for treatment of tibial plateau fractures (TPF). This retrospective study was designed to introduce this novel technique, ASIN, as well as to describe the initial experience and verify the effectiveness when ASIN was used for the management for TPF. Methods: A cohort of 19 cases with closed TPF aged from 18–70 years with at least 23 months follow‐up from November 2008 to September 2013 was analyzed retrospectively. All patients underwent the ASIN procedure, which was performed by the same group of surgeons. Perioperative and postoperative parameters like the measurement of radiographic pictures, surgical data, and clinical function were recorded including the changes in treatment. A modified Hohl–Luck radiological and functional score combined with the Hospital for Special Surgery (HSS) score were applied to evaluate the final results and to provide reliable data through the whole procedure when applying the ASIN procedure. Results: The patients were followed up regularly for an average of 26.3 (range, 23–34) months. All patients achieved a bony union at an average of 15.1 weeks with no incidences of malunion, nonunion, or infection. Anatomical reduction of the articular surface was obtained in 16 patients. No secondary failure of fixation occurred. The mean postoperative knee flexion was 122.9°. The modified Hohl–Luck radiological and functional score was excellent and good, respectively, in 16 patients. The mean HSS score was 89.4. Conclusion: The angle stable interlocking intramedullary nail system turned out to be a viable alternative protocol in the treatment of tibia plateau fractures and provided satisfactory results, with good fracture reduction, biomechanical fixation, low rates of complications, and passable postoperative knee function. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of S-(−)-pantoprazole (PPZ) sodium injections following single and multiple intravenous doses in healthy Chinese subjects.Methods: The dosage groups were set as followed: 20 mg of single and multiple intravenous administration of S-(−)-PPZ, 40 mg of single and multiple intravenous administration of S-(−)-PPZ or pantoprazole, and 80 mg of single dosage group of S-(−)-PPZ. Subjects were sampled for pharmacokinetic analysis and were monitored for 24-h intragastric pH prior to and 48-h intragastric pH after administration for the pharmacodynamic study. The pharmacokinetic and pharmacodynamic parameters were compared between S-(−)-PPZ and PPZ. Safety was evaluated on the basis of adverse events, vital signs, laboratory tests, and physical examination.Results: All adverse events were mild and of limited duration. Maximum plasma concentration and area under the concentration-time curve for S-(−)-PPZ were dose proportional over the range of 20–80 mg following a single intravenous administration. Elimination rate constant and half-life observed statistical difference from a single dose to multiple doses in 40 mg of S-(−)-PPZ groups. After administration of a single dose, the mean 24-h intragastric pH value was observed higher in 80-mg group than in 40- and 20-mg groups. Slightly increase of intragastric pH was found after a single dose of 40 mg S-(−)-PPZ than 40 mg PPZ; however, the differences were not statistically significant.Conclusions: Twice daily of 40 mg S-(−)-PPZ sodium injections is effective in achieving satisfying acid inhibition. Compared with plasma R-(+)-PPZ levels, most subjects presented more potent and prolonged suppression of gastric acid of S-(−)-PPZ, while a few subjects showed faster metabolic rate of S-(−)-PPZ in vivo. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of dexlansoprazole injection in healthy subjects. Methods: Dexlansoprazole (20-90 mg) or lansoprazole (30 mg) was administrated intravenously to healthy male and female volunteers. All the subjects were sampled for pharmacokinetic (PK) analysis and 64 of them were monitored for 24-h intragastric pH prior to and after administration in the pharmacodynamic (PD) study. Results: Maximum plasma concentration (C) and area under the concentration-time curve (AUC) for dexlansoprazole injection was dose-proportional over the range of 20-90 mg following a single intravenous administration. Total clearance and half-life (t) was independent of dose, and ranged from 4.69 L/h to 5.85 L/h and from 1.24 h to 2.17 h, respectively. A single dose of dexlansoprazole (30 mg) resulted in higher gastric pH compared to that of lansoprazole, evidenced by a mean 24-h gastric pH of 6.1 ± 1.2 (lansoprazole: 5.4 ± 1.1) and 24-h gastric pH > 6 post drug dose holding time of 64.2 ± 21.0% (lansoprazole: 49.5 ± 21.5%). Conclusion: Dexlansoprazole injection was safe and well tolerated for up to 5-day repeated intravenous administration dose of 30 mg. The recommended dosage for dexlansoprazole injection is 30 mg for an adequate gastric acid control. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess the prevalence and risk factors for hypertensive disorders and to study the main pregnancy outcomes in the Beijing area of China.Study Design: This study randomly sampled 15 hospitals in Beijing from Jun 2013 to Nov 2013 and evaluated 15 194 deliveries. Logistic regression analysis was used to study the association between risk factors and hypertensive disorders. Pregnancy outcomes included preterm birth, cesarean delivery and small for gestational age (SGA).Results: The prevalence of hypertensive disorders, preeclampsia (PE) and severe PE was 4.4, 2.7 and 1.8%, respectively. The risk factors for hypertensive disorders and severe PE were maternal body mass index before pregnancy, gestational weight gain (GWG), gestational diabetes and pre-gestational diabetes, and third trimester cholesterol (CHOL) levels. First trimester high-density lipoprotein was a protective factor for severe PE. The incidence of hypertensive disorders increased with maternal age. Preterm delivery, cesarean delivery and small infant size for gestational age were more prevalent in the severe PE group compared with the non-hypertensive group.Conclusions: In the Beijing area of China, maternal body mass index before pregnancy, GWG, maternal complications of gestational diabetes and pre-gestational diabetes, and third trimester CHOL levels are risk factors for both hypertensive disorders of pregnancy and severe PE. First trimester high-density lipoprotein is a protective factor for severe PE. Severe preeclampsia leads to a higher incidence of preterm delivery, cesarean delivery and SGA infants. [ABSTRACT FROM AUTHOR]

Objective: To estimate the risk of adverse maternal and perinatal outcomes in women with different pre-pregnancy body mass index (BMI).Methods: We conducted a cohort study with 14 451 singleton pregnancies in 15 medical centers in Beijing between 20 June 2013 and 30 November 2013 using cluster random sampling. We divided participants into four groups based on pre-pregnancy BMI: Group A (underweight): BMI < 18.5 kg/m(2), Group B (normal): 18.5-23.9 kg/m(2), Group C (overweight): 24-27.9 kg/m(2), Group D (obesity): ≥28 kg/m(2). We used multivariate analysis to evaluate the association of the risk of adverse pregnancy outcomes and pre-pregnancy BMI.Results: The prevalence of maternal overweight and obesity was 14.82% (2142/14 451) and 4.71% (680/14 451) in the study population, respectively. Higher pre-pregnancy BMI is associated with higher prevalence of gestational diabetes (GDM), macrosomia, Cesarean section (C-section), preeclampsia and postpartum hemorrhage. Pre-pregnancy overweight or obesity increases the risk of adverse pregnancy outcomes, regardless of GDM status.Conclusions: Pre-pregnancy overweight or obesity is associated with increased risk of adverse pregnancy outcomes. Nutrition counseling is recommended before pregnancy in women who have overweight or obesity. [ABSTRACT FROM AUTHOR]

Several reports describing anaphylactic shock following treatment of cardiovascular and cerebrovascular diseases with Chinese herbal injections were described. Our analysis of these reports showed that anaphylactic shock caused by traditional Chinese medicine (TCM) injections for the treatment of cardiovascular and cerebrovascular diseases is common but also sometimes fatal. Therefore, we proposed the following four suggestions for improving the clinical safety of delivering Chinese herbal injections and reducing the occurrence of allergic shock. First, patients with cardiovascular and cerebrovascular diseases are at high risk, so they should only be given TCM injections after a doctor’s diagnosis and approval. Second, people in allergic groups can suffer anaphylactic shock, so vigilance is important in the treatment of all age groups, although even more caution should be exercised when treating children or elderly people. In fact, TCM injections may not be appropriate for those age groups, so that they should be carefully considered before treatment. Third, no significant gender differences have been noted in patients with anaphylactic shock, so all patients should be carefully monitored, irrespective of gender. Fourth, the timeframe in which different drugs cause anaphylactic shock varies; thus, patients should be observed as long as possible. [ABSTRACT FROM AUTHOR]

For optical measurement of high-temperature components, it is a challenge to analyze the measurement error caused by light refraction due to the inhomogeneous distribution of the air refractive index. Aiming at the problem of line laser measurement under the high-temperature environment, a method for analysis of line laser measurement error on high-temperature surfaces combined with backward ray tracing technology is proposed. The temperature field of the air is simulated based on the heat conduction theory, and the air refractive index is obtained according to the classical empirical formula. Combining with the refraction law of light and the laser triangulation method, the deviation of the spatial position corresponding to each point on the charged-coupled device is calculated. The imaging principle of backward ray tracing is applied to obtain the actual imaging point, and the measurement error of the sensor is calculated. The experiment results prove that the proposed method can effectively evaluate the line laser measurement error under the high-temperature environment. We analyze the system error of the laser sensor under high-temperature conditions and promote the development of high-temperature components on-machine measurement. [ABSTRACT FROM AUTHOR]

• 90 NAC transcription factors (TFs) were identified in the eggplant genome. • Conserved motifs, conserved domains and gene structure of SmNAC genes were resolved. • Chromosomal location, gene replication and synteny of SmNAC genes were investigated. • Expression patterns of SmNAC genes were analyzed in vegetative and reproductive organs, at different developmental stages. • qRT-PCR analyses of ATAF subfamily members, exhibited a large diversity in the regulation of different abiotic stresses. NAC proteins, as one of the largest plant-specific transcription factors, play key roles in plant growth, development process, and various abiotic/biotic stresses. In this study, 90 NAC transcription factors (TFs) were identified in the eggplant genome, among them, 80 NAC genes from eggplant (SmNAC) were anchored unevenly in 12 chromosomes, but 10 SmNAC genes were mapped on unanchored scaffolds. Phylogenetic analysis indicated that only fifty-nine SmNAC genes were divided into 14 different subfamilies. Gene structure analysis revealed that the number of exons ranged from 1 to 16. Motif analysis revealed that the identified SmNAC transcription factors included the conserved NAC domain and motif2 was the conserved motif. In aspects of gene duplication analysis, five pairs of tandem replications and three pairs of fragment replications were identified in eggplant genome. Subsequently, 49 SmNAC genes were collinear with NAC genes from Arabidopsis or tomato, moreover, seven SmNAC genes were collinear with NAC genes in other two species. In addition, expression patterns of SmNAC genes were analyzed in vegetative and reproductive organs, at different developmental stages. Nine genes were not expressed in all of the examined developmental stages, 36 SmNAC genes were ubiquitously expressed in all eggplant organs/tissues, but differentially expressed in different tissues, and other 45 SmNAC genes detected in some tissues declared their involvement in the growth and development of certain tissues. Following further qRT-PCR analysis of SmNAC19, SmNAC31 and SmNAC75 , belonging to ATAF subfamily, exhibited a large diversity in expression patterns, indicating their involvement in the regulation of different abiotic stresses. This study would help to further understand and enrich the physiological function of the SmNAC gene family in eggplant, and could provide high-quality genetic resources for eggplant genetics and breeding. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the therapeutic effects of epigallocatechin-3-gallate (EGCG) administered by subarachnoid injection following spinal cord injury (SCI) in rats and to explore the underlying mechanism. Sprague-Dawley rats were randomly divided into four groups of 12 as follows: a sham group (laminectomy only); a control group; a 10 mg/kg EGCG-treated group; and a 20 mg/kg EGCG-treated group. SCI was induced in the rats using the modified weight-drop method (10 g × 4 cm) at the T10 (10th thoracic vertebral) level. EGCG (10 or 20 mg/kg) or vehicle as control was administered by subarachnoid injection at lumbar level 4 immediately after SCI. Locomotor functional recovery was assessed during the four weeks post-operation using open-field locomotor tests and inclined-plane tests. At the end of the study, the segments of spinal cord encompassing the injury site were removed for histopathological analysis. Immunohistochemical and Western blot analyses were performed to observe the expression of: the B cell CLL/lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). The results showed that the EGCG-treated animals had significantly better recovery of locomotor function, less myelin loss, greater Bcl-2 expression and attenuated Bax expression. In addition, the EGCG treatment significantly increased the expression of BDNF and GDNF after SCI. These findings suggest that EGCG treatment can significantly improve locomotor recovery, and this neuroprotective effect may be related to the up-regulation of BDNF and GDNF, and the inhibition of apoptosis-related proteins. Therefore, EGCG may be a promising therapeutic agent for SCI. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective case series. Objective: To evaluate the accuracy of screw fixation using intraoperative three-dimensional fluoroscopy-based navigation (ITFN) and to assess the clinical outcomes of this treatment regimen. Summary Of Background Data: The surgical management of symptomatic os odontoideum poses considerable difficulties due to the highly variable anatomy of the upper cervical spine and surrounding neurovascular structures. Various methods have been described for the treatment of symptomatic os odontoideum, all of which have limitations. Methods: Nineteen patients with symptomatic os odontoideum were investigated. Pain scores were assessed using the visual analogue scale. Myelopathy was assessed using the Nurick scale and Odom's criteria. Radiological imaging was carried out in all patients for diagnosis and to assess the atlantodens interval, space available for cord, and presence of intramedullary hyperintensity signals on T2-weighted images at the C1-C2 level. Posterior stabilization was performed for all patients by using ITFN. Results: The mean Nurick score improved from 2.3 before surgery to 0.7 at the time of follow-up. The mean follow-up period was 34.7 months (range, 12-65 mo). According to Odom's criteria, outcomes were as follows: excellent, 47%; good, 37%; fair, 11%; and poor, 5%. All patients with preoperative neck pain had symptom relief or improvement, with all of these patients having more than 83.7% improvement in visual analogue scale scores. The mean preoperative space available for cord value of 9.3 mm improved to 17.7 mm. Solid fusion and reduction of atlantoaxial dislocation were achieved in every patient without screw failure. Sixty screws were placed in 19 patients. Two C2 polyaxial screws in 2 patients and 1 transarticular screw in 1 patient slightly penetrated the transverse foramen with no vascular injury and clinical sequelae. Conclusion: ITFN is a safe, accurate, and effective tool for screw placement in patients with symptomatic os odontoideum. [ABSTRACT FROM AUTHOR]

Conclusion: Elevated levels of hypoxia-inducible factor 1α (HIF-1α) in middle ear effusion may play an important role in the pathogenesis of bone conduction impairment associated with otitis media with effusion (OME). The mechanism may be related to the up-regulation of nitric oxide (NO) expression. Objectives: This study was undertaken to investigate the role of HIF-1α in the pathogenesis of sensorineural hearing loss associated with OME. Methods: One hundred and eight OME patients were divided into two groups: OME without bone conduction impairment (group 1) and OME with bone conduction impairment (group 2). The levels of HIF-1α, NO, and quinolinic acid (QUIN) in the middle ear effusion and serum of these patients were investigated. The relationship between these factors and the bone conduction threshold (BCT) differences were analyzed. Results: The levels of HIF-1α and NO concentrations in the middle ear effusion were found to be significantly higher in group 2 than in group 1 (both p < 0.05). The OME patients' BCT differences at 4000 Hz were correlated with the levels of HIF-1α and the NO concentrations in the middle ear effusion. Furthermore, the HIF-1α levels were correlated with the levels of NO but not with the levels of QUIN in the effusion. [ABSTRACT FROM AUTHOR]

Conclusion: Elevated levels of hypoxia-inducible factor 1α (HIF-1α) in middle ear effusion may play an important role in the pathogenesis of bone conduction impairment associated with otitis media with effusion (OME). The mechanism may be related to the up-regulation of nitric oxide (NO) expression. Objectives: This study was undertaken to investigate the role of HIF-1α in the pathogenesis of sensorineural hearing loss associated with OME. Methods: One hundred and eight OME patients were divided into two groups: OME without bone conduction impairment (group 1) and OME with bone conduction impairment (group 2). The levels of HIF-1α, NO, and quinolinic acid (QUIN) in the middle ear effusion and serum of these patients were investigated. The relationship between these factors and the bone conduction threshold (BCT) differences were analyzed. Results: The levels of HIF-1α and NO concentrations in the middle ear effusion were found to be significantly higher in group 2 than in group 1 (both p < 0.05). The OME patients' BCT differences at 4000 Hz were correlated with the levels of HIF-1α and the NO concentrations in the middle ear effusion. Furthermore, the HIF-1α levels were correlated with the levels of NO but not with the levels of QUIN in the effusion. [ABSTRACT FROM AUTHOR]

Abstract: A sensitive and highly selective liquid chromatography tandem mass spectrometric (LC/MS/MS) method was developed and validated for the determination of ciclesonide (CIC) and its active metabolite, desisobutyryl-ciclesonide (des-CIC), in human plasma. Plasma samples were extracted using methyl tert-butyl ether with mifepristone as an internal standard (IS). Separation was carried out on a C18 column using a mixture of 0.1% formic acid solution and methanol as the mobile phase with linear gradient elution. The detection was operated with positive atmospheric pressure chemical ionization (APCI) by selective multiple reaction monitoring (SRM). The chief benefit of the present method was the high sensitivity, with the lower limit of quantification (LLOQ) as low as 10pg/mL and the linearity ranging from 10 to 10,000pg/mL for both CIC and des-CIC. The method was fully validated and successfully applied to determine CIC and des-CIC simultaneously in human plasma and proved to be suitable for phase I clinical pharmacokinetic study of inhaled ciclesonide in healthy Chinese volunteers. [Copyright &y& Elsevier]

Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease. Clinically, no efficient assay protocols have been available. In this study, we aimed to develop an oligonucleotide biochip specialized for detection of known base substitution mutations in mitochondrial DNA causing LHON and to investigate frequencies of LHON relevant variants in Anhui region of China. Thirty-two pairs of oligonucleotide probes matched with the mutations potentially linked to LHON were covalently immobilized. Cy5-lablled targets were amplified from blood DNA samples by a multiplex PCR method. Two kinds of primary mutations 11778 G > A and 14484 T > C from six confirmed LHON patients were interrogated to validate this biochip format. Further, fourteen Chinese LHON pedigrees and twenty-five unrelated healthy individuals were investigated by the LHON biochip, direct sequencing and pyrosequencing, respectively. The biochip was found to be able efficiently to discriminate homoplasmic and heteroplasmic mtDNA mutations in LHON. Biochip analysis revealed that twelve of eighteen LHON symptomatic cases from the 14 Chinese pedigree harbored the mutations either 11778G > A, 14484T > C or 3460G > A, respectively, accounting for 66.7%. The mutation 11778G > A in these patients was homoplasmic and prevalent (55.5%, 10 of 18 cases). The mutations 3460G > A and 3394T > C were found to co-exist in one LHON case. The mutation 13708G > A appeared in one LHON pedigree. Smaller amount of sampling and reaction volume, easier target preparation, fast and high-throughput were the main advantages of the biochip over direct DNA sequencing and pyrosequencing. Our findings suggested that primary mutations of 11778G > A, 14484T > C or 3460G > A are main variants of mtDNA gene leading to LHON in China. The biochip would easily be implemented in clinical diagnosis. [ABSTRACT FROM AUTHOR]

Since the publication of our article [1] it has come to our attention that there was an error in Figure 4 in which the bottom left immunochemistry panel Control/Bax was a duplication of the bottom right immunohistochemistry panel EGCG/GDNF in Figure 3. [ABSTRACT FROM AUTHOR]