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Aims Dexmedetomidine is highly specific α2-adrenoceptor agonist. A single bolus of dexmedetomidine can achieve clinical therapeutic effect. Therefore, it is essential to know the safety margin between the clinical effectiveness dosages of dexmedetomidine and its side effect. Methods A total of 42 patients who underwent elective thyroidectomy were enrolled in this study. Dexmedetomidine was given as a single bolus injection 30 min towards the end of surgery. The up-and-down sequential schedule was used in this study. The starting dose of dexmedetomidine was set at 0.1 μg/kg in the first patient and the next patient would then receive a dose of dexmedetomidine decremented by 0.05 μg/kg if the prior patient's baseline heart rate (HR) had a decrease of ≥20% and/or mean arterial blood pressure (MAP) increase or decrease of ≥20%, otherwise, the following patient would receive an incremental 0.05 μg/kg dose of dexmedetomidine. The analytic techniques of linear, linear-logarithmic, exponential regressions and centred isotonic regression were used to determine the ED50 of dexmedetomidine and the residual standard errors were calculated for the comparison of goodness of fit among the different models. Results The median (interquartile range [range]) lowest HR was 57 beats/min (53-63.3[46-76]) with an average HR decrease of 8.0 beats/min (5-13 [4 to 23]). The median (interquartile range [range]) highest MAP was 98 mmHg (91.8-105 [83-126]) with a MAP increase of 10.0 mmHg (6.8-18.0 [2-24]). The ED50 (95% confidence interval) from 4 different statistical approaches (linear, linear-logarithmic, exponential regressions and centred isotonic regression) were 0.262 μg/kg (0.243, 0.306), 0.252 μg/kg (0.238, 0.307), 0.283 μg/kg (0.238, 0.307), and 0.278 μg/kg, respectively. Among the 4 models, the exponential regression had the least residual standard error (0.03618). Conclusion The ED50 derived from 4 statistical models for an intravenous bolus of dexmedetomidine without significant haemodynamic effects was distributed in a narrow range of 0.252-0.283 μg/kg, and the exponential regression was the model to best match the study data.

A rapid, sensitive, and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of dexmedetomidine in children's plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2mL of acetonitrile to a 0.1mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient elution. The total run time was 3.1min and the elution of dexmedetomidine was at 1.24min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring mode using the respective transitions m/z 201.3→95.1 for dexmedetomidine and m/z 204.2→98.0 for the internal standard, respectively. The calibration curve was linear over the range of 0.05-10ng/mL with a lower limit of quantitation of 0.05ng/mL. Mean recovery rate of dexmedetomidine in plasma was in the range of 86.7-89.1%. Intra-day and inter-day precision were both

Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist with sedative and analgesic properties which is also used in pediatric anesthesia. Although the pharmacokinetics of dexmedetomidine have been studied in pediatric patients, there are no data for Chinese children available. As alterations in pharmacokinetics due to ethnicity cannot be ruled out, it was the aim of this study to characterize the pharmacokinetics of dexmedetomidine in Chinese pediatric patients. Thirty-nine children aged 1–9 years undergoing surgery were enrolled in the study. Dexmedetomidine was administered as short intravenous infusion of 1–2 µg/kg in 10 min. Venous blood samples were drawn until 480 min after stopping of infusion. Dexmedetomidine plasma concentrations were measured with high-performance liquid chromatography and mass spectrometry. Pharmacokinetic modeling was performed by population analysis using linear compartment models. Data of 36 patients (age 1–9 years, weight 10–27 kg) were analyzed. The pharmacokinetics of dexmedetomidine were best described by a two-compartment model with an allometric power model and estimates standardized to 70 kg body weight. The population estimates (95 % CI) per 70 kg bodyweight were: clearance 36.2 (33.3–41.1) l/h, central volume of distribution 84.3 (70.3–91.4) l, intercompartmental clearance 82.8 (63.6–136.6) l/h, peripheral volume of distribution 114 (95–149) l, and terminal half-life 4.4 (3.6–5.3) h. Age did not show any influence on weight-adjusted parameters. Chinese children showed a similar clearance, but larger volumes of distribution and longer terminal half-life when compared to studies in Caucasians. ChiCTR-OPC-14005659.

Aims Isoflurane may not only accelerate the process of Alzheimer's disease (AD), but increase the risk of incidence of postoperative cognitive dysfunction (POCD). However, the underlying mechanisms remain unknown. This study was designed to investigate whether isoflurane contributed to the POCD occurrence through A1 adenosine receptor (A1AR) in aged mice. Methods We assessed cognitive function of mice with Morris water maze (MWM) and then measured expression level of two AD biomarkers (P-tau and Aβ) and a subtype of the NMDA receptor (NR2B) in aged wild-type (WT) and homozygous A1 adenosine receptor (A1AR) knockout (KO) mice at baseline and after they were exposed to isoflurane (1.4% for 2 hours). Results For cognitive test, WT mice with isoflurane exposure performed worse than the WT mice without isoflurane exposure. However, A1AR KO mice with isoflurane exposure performed better than WT mice with isoflurane exposure. WT mice exposed to isoflurane had increased levels of Aβ and phosphorylated tau (P-tau). Levels of Aβ and P-tau were decreased in A1AR KO mice, whereas no differences were noted between KO mice with and without isoflurane exposure. NR2B expression was inversely related to that of P-tau, with no differences found between KO mice with and without isoflurane exposure. Conclusions We found an association between isoflurane exposure, impairment of spatial memory, decreasing level of NR2B, and increasing levels of A-beta and P-tau, presumably via the activation of the A1A receptor.

The adsorption and dissociation processes of H 2 O on the Ga-rich GaAs(0 0 1)-(4 × 2) surface have been investigated at the PBE/def2-TZVPP and PBE-D3(BJ)/def2-TZVPP levels of theory. A Ga 7 As 8 H 11 cluster has been employed to model the Ga-rich GaAs(0 0 1)-(4 × 2) surface. According to our computations, a chemisorbed state is formed initially. And then, the adsorbed H 2 O molecule will dissociate to OH radical and H atom after overcoming the corresponding barriers on the Ga 7 As 8 H 11 cluster. Furthermore, the functionals of B3LYP, B3LYP-D3(BJ), and M06-2X have also been compared for evaluating the relative energies.

Summary Background The objective of this study was to determine ED50 and ED95 of remifentanil for intubation combined with propofol in nonparalyzed Chinese children. Methods Forty-seven American Society of Anesthesiologists Class I children aged 4–11 years weighing 14–33.5 kg underwent general anesthesia with 2.5 mg·kg−1 of intravenous propofol followed by remifentanil in Wenzhou, China. The initial dose of remifentanil was 2.5 μg·kg−1 injected over 60 s. Intubation was attempted 30 s after the completion of remifentanil injection. Level of difficulty to intubate was graded on a scoring system. If the initial intubation condition was deemed satisfactory, subsequent remifentanil doses were decreased by 0.25 μg·kg−1. If the intubating condition was deemed unsatisfactory, subsequent remifentanil doses were increased by 0.25 μg·kg−1. Mean arterial pressure, heart rate, and pulse oximetry were documented before and after induction, immediately after intubation, and 1 min after intubation. Results The ED50 of remifentanil used to render a satisfactory intubating condition used in combination with 2.5 mg·kg−1 of propofol in nonparalyzed Chinese children was 2.30 μg·kg−1 (95% confidence interval: 2.28–2.31 μg·kg−1), and the ED95 is 2.75 μg·kg−1 (95% confidence interval: 2.59–3.35 μg·kg−1). These doses were lower than previously reported. Conclusion When used in combination with 2.5 mg·kg−1 of intravenous propofol, ED50 and ED95 of remifentanil for adequate intubation in nonparalyzed children were lower than previously reported, at 2.30 and 2.75 μg·kg−1, respectively.

Breast cancer is the most prevalent cancer and the leading cause of cancer‑associated mortalities among women worldwide today. Accumulating evidence suggested that miR‑372 may serve important roles in the initiation and development of various human cancers. However, the role of miR‑372 in breast cancer remains unknown. The present study demonstrated that the expression level of miR‑372 in human breast cancer tissues and cell lines is significantly reduced compared with normal breast tissues cell lines. Furthermore, results of functional assays indicated that miR‑372 inhibits cell proliferation and induces apoptosis in the MCF‑7 human breast cancer cell line. E2F1 was identified as a direct functional target of miR‑372 in breast cancer. In conclusion, the findings revealed that miR‑372 may have the potential to act as a novel molecule for the diagnosis and therapy of patients with breast cancer.

Background Etomidate is a rapid hypnotic intravenous anesthetic agent. The major side effect of etomidate is the reduced plasma concentration of corticosteroids, leading to the abnormal reaction of adrenals. Cortisol and testosterone biosynthesis has similar biosynthetic pathway, and shares several common steroidogenic enzymes, such as P450 side chain cleavage enzyme (CYP11A1) and 3β-hydroxysteroid dehydrogenase 1 (HSD3B1). The effect of etomidate on Leydig cell steroidogenesis during the cell maturation process is not well established. Methodology Immature Leydig cells isolated from 35 day-old rats were cultured with 30 μM etomidate for 3 hours in combination with LH, 8Br-cAMP, 25R-OH-cholesterol, pregnenolone, progesterone, androstenedione, testosterone and dihydrotestosterone, respectively. The concentrations of 5α-androstanediol and testosterone in the media were measured by radioimmunoassay. Leydig cells were cultured with various concentrations of etomidate (0.3–30 μM) for 3 hours, and total RNAs were extracted. Q-PCR was used to measure the mRNA levels of following genes: Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Srd5a1, and Akr1c14. The testis mitochondria and microsomes from 35-day-old rat testes were prepared and used to detect the direct action of etomidate on CYP11A1 and HSD3B1 activity. Results and Conclusions In intact Leydig cells, 30 μM etomidate significantly inhibited androgen synthesis. Further studies showed that etomidate also inhibited the LH- stimulated androgen production. On purified testicular mitochondria and ER fractions, etomidate competitively inhibited both CYP11A1 and HSD3B1 activities, with the half maximal inhibitory concentration (IC50) values of 12.62 and 2.75 μM, respectively. In addition, etomidate inhibited steroidogenesis-related gene expression. At about 0.3 μM, etomidate significantly inhibited the expression of Akr1C14. At the higher concentration (30 μM), it also reduced the expression levels of Cyp11a1, Hsd17b3 and Srd5a1. In conclusion, etomidate directly inhibits the activities of CYP11A1 and HSD3B1, and the expression levels of Cyp11a1 and Hsd17b3, leading to the lower production of androgen by Leydig cells.

To explore the effects of propofol target controlled infusion (TCI) plus a low concentration of sevoflurane inhalation induction for the removal of tracheobronchial foreign body in children.After the approval of the hospital ethics committee, a total of 90 patients, aged 9 - 36 months old and weighted 8 - 17 kg, were randomly divided into 3 groups: group A, group B and group C. Propofol TCI plus a low concentration of sevoflurane inhalation induction was administered in group A while ketamine or fentanyl plus propofol TCI in group B or C respectively. Effects of anesthesia, complications and recovery durations were observed.The incidence of severe breathholding and bucking during inserting bronchoscope was 1 case in group A, 7 in group B and 5 in group C. There were significant differences between groups A and B (P0.05). The minimal intra-operative SpO2 in group B or group C was lower than that in group A (P0.01). The cases for intra-operative SpO295% in group B or group C were more than that in group A (P0.01). And the maximal target concentration of propofol was significantly higher than that in group A (P0.01). Ten cases in group B had laryngeal stridor and dyspnea during inspirations post-operatively and occurred more frequently than those in group A or C (P0.01). As compared with group A and C, post-operative staying lengths and recovery durations were significantly longer in those in group B (P0.01).Propofol TCI plus a low concentration of sevoflurane inhalation induction is both safe and practical for the controlled removal of tracheobronchial foreign body in children.

To study the effect of a pediatric TCI patent system for propofol plus remifentanil in pediatric short-duration surgery with laryngeal mask airway (LMA) anesthesia.A total of 120 pediatric patients underwent short-duration elective surgery, aged 3 - 9 years old, weighted 13 - 26 kg, ASAI grade, were randomly divided into 3 groups (n = 40 each). The propofol concentrations of effect compartment were set at 2 µg/ml in Group A, 3 µg/ml in Group B and 4 µg/ml in Group C. The remifentanil initial concentration of plasma compartment was 2 ng/ml and increased stepwise by 0.5 ng/ml until a successful insertion of LMA. The remifentanil concentration was recorded when LMA was successfully inserted and the cases were numerated at the each remifentanil concentration. Heart rate (HR), mean arterial pressure (MAP), BIS (bispectral index) values and postoperative adverse events were also recorded at the time points of pre-induction (T0), 2 min post-remifentanil TCI (T1), LMA insertion (T2), skin incision (T3), 5 min post-skin incision (T4), 10 min post-skin incision, (T5) and beginning surgery (T6).The satisfactory ratios of a successful insertion of LMA were highest in remifentanil 3.0 ng/ml (AR subgroup), 2.5 ng/ml (BR subgroup) and 2.0 ng/ml (CR subgroup) respectively. The laryngeal mask satisfactory ratio was high in BR subgroup (P0.05). There were significantly differences of T1-T5 values of HR, MAP and BIS in AR and CR subgroups (P0.05), but not in BR subgroup. The above-mentioned monitoring indices at T2 in AR subgroup and T3 in CR subgroup were significantly higher than those in BR subgroup. There were more adverse reactions in CR and AR subgroups versus BR subgroup (P0.05).The patented system for propofol 3 µg/ml effect compartment concentration plus remifentanil 2.5 ng/ml plasma concentration TCI displays stable hemodynamics, less stress, fewer complications and better clinical outcomes in pediatric short-duration surgery with LMA anesthesia.

To discuss the effect of the new target controlled infusion (TCI) system in Chinese children undergoing minor operation and compared with TCI system with Marsh parameters.Ninety ASA I, aged 3 - 5 yrs children undergoing elective unilateral high ligation of hernial sac under general anesthesia were randomly divided into group L (n = 45) and group M (n = 45) 2 groups. All subjects were unpremedicated. Systolic blood pressure (SBP), diastolic blood pressure (DBP), ECG, SpO2 and BIS were monitored. Patients of Group L and group M were anesthetized with propofol by Lian propofol TCI system and Marsh system respectively, combined with regional block. The target plasma concentration of TCI system was set at 6 microg/ml initially and up-regulated 1 microg/ml gradually if obvious body movement occurred while skin incision. If the target plasma concentration up to 8 microg/ml but there still had body movement, the TCI venous anesthesia was replaced by inhaled anesthesia. HR, RR, SBP, DBP and BIS were recorded in time points of baseline (T(0)), after the induction (T(1)), skin incision (T(2)), 3, 5 min after skin incision (T(3), T(4)), the end of operation (T(5)). Complications, the awakening time and the number of cases which anesthetized with different propofol plasma concentrations or inhaled anesthesia were recorded respectively as well.The number of cases which completed the operation under TCI plasma concentration 6 microg/ml in group L were significantly more than those in group M (P0.01). There were significantly different of T(1)-T(4) values of HR, RR, SBP, DBP and BIS in group M (P0.05), but not in group L. Compared with group L, T(2)-T(4) values of HR, RR, SBP, DBP and BIS were higher in group M (P0.05 or 0.01). Complications were lower in group L than those in group M.Compared with Marsh system, propofol 6 microg/ml plasma concentration with the new target controlled infusion system applied in Chinese children undergoing unilateral high ligation of hernial sac could maintain stable hemodynamics, less stress reaction and complications.