Animals ; Antioxidants ; physiology ; Dehydroepiandrosterone ; physiology ; Lipid Metabolism ; physiology ; Male ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of propofol on brain regions at different sedation levels and the association between changes in brain region activity and loss of consciousness using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and bispectral index (BIS) monitoring.

METHODSForty-eight participants were enrolled at Peking Union Medical College Hospital from October 2011 to March 2012 and randomly assigned to a mild or a deep sedation group using computer- generated random numbers. Preliminary tests were performed a week prior to scanning to determine target effect site concentrations based on BIS and concomitant Observer's Assessment of Alertness/Sedation scores while under propofol. Within one week of the preliminary tests where propofol dose-response was established, BOLD-fMRI was conducted to examine brain activation with the subject awake, and with propofol infusion at the sedation level.

RESULTSMild propofol sedation inhibited left inferior parietal lobe activation. Deep sedation inhibited activation of the left insula, left superior temporal gyrus, and right middle temporal gyrus. Compared with mild sedation, deep propofol sedation inhibited activation of the left thalamus, precentral gyrus, anterior cingulate, and right basal nuclei.

CONCLUSIONMild and deep propofol sedation are associated with inhibition of different brain regions, possibly explaining differences in the respective loss of consciousness processes.

Adult ; Brain ; drug effects ; Consciousness Monitors ; Deep Sedation ; Dose-Response Relationship, Drug ; Humans ; Hypnotics and Sedatives ; pharmacology ; Male ; Propofol ; pharmacology

OBJECTIVETo compare the accuracies of cerebral state index (CSI) and bispectral index (BIS) in sedation monitoring during target control infusion of midazolam.

METHODSTwenty informed adult male volunteers were intravenously administered with midazolam through plasma target control infusion from 30ng/ml (in increments of 10ng/ml every time) until they became unresponsive to tactile stimulation (i. e., mild prodding or shaking). The BIS and CSI were continuously recorded simultaneously. Sedation was assessed using the Observers' Assessment of Alertness/Sedation (OAA/S) scale at each time when Ct equaled to Ce. The electroencephalogram (EEG) parameters were correlated with the OAA/S scores using nonparametric Spearman's correlation analysis. The prediction probabilities were calculated at the points of lost of verbal contact (LVC) and lost of responses to stimulus (LOR). BIS05, BIS50, BIS95, and CSI05, CSI50, CSI95 were also calculated for LVC and LOR.

RESULTSBIS and CSI were well correlation with OAA/S scales during both the onset and recovery phases. When the sedation level increased, BIS and CSI progressively decreased. The prediction probabilities of BIS and CSI were 84%, 74% for LVC and 79%, 68% for LOR, while the BIS05, BIS50, and BIS95 as well as CSI05, CSI50, and CSI95 were 85.5, 60.6, and 35.7 (for BISs) and 82.2, 65.2, and 30.3 (for CSIs) at the point of LVC and 79.7, 47.6, and 15.6 (for BISs) and 75.9, 43.4, and 11 (for CSIs) at the point of LOR.

CONCLUSIONSBoth CSI and BIS seem to be useful parameters for assessing midazolam-induced sedation. BIS is superior in the prediction of LVC and LOR.

Adult ; Anesthetics, Intravenous ; administration & dosage ; therapeutic use ; Brain ; drug effects ; physiology ; Conscious Sedation ; methods ; Consciousness ; drug effects ; Electroencephalography ; Humans ; Infusions, Intravenous ; Male ; Midazolam ; administration & dosage ; therapeutic use ; Young Adult

OBJECTIVETo observe the effects of different concentrations of propofol on brain regions activated by mechanical stimuli, and then to investigate the analgesic effect of propofol.

METHODSTwenty healthy male volunteers were randomly divided into two groups: light anesthesia group (group L) (BIS 60-80) and deep anesthesia group (group D)(BIS 40-60). Propofol was administrated by target controlled infusion system in pilot study. The target effect site concentration (ESC) of propofol was defined as the average of the ESC from BIS 80 to 60 or BIS 60 to 40 in group L or group D respectively. Mechanical stimuli were applied using von Frey filaments at the center of the left foot, and the pain threshold and VAS scores were evaluated. fMRI examinations were taken 1 week after pilot study with the following sequences: structure imaging+ functional imaging: functional imaging=stimulus sequence+propofol sequence, in which the stimulus sequence was 6 × (20 s on + 20 s off). This sequence was repeated after propofol sequence.

RESULTSAs shown by fMRI, in group L, active brain regions of (the second stimulation-the first stimulation, P2-P1) were seen in cingulate gyrus, thalamus, and cerebellum, while active brain regions of (P1-P2) were seen in temporal lobe, frontal gyrus, and occipital lobe. In group D, the active brain region of (P2-P1) was only seen in cerebellum, while active brain regions of (P1-P2) were seen in cingulate gyrus and thalamus. Active brain regions of (deep-low) with propofol infusion in response to vFFs stimulation were observed in cerebellum.

CONCLUSIONSPropofol at different concentrations has different effect on the activation of brain regions. It may exert its analgesic effect via different mechanisms.

Adult ; Brain ; physiology ; Humans ; Magnetic Resonance Imaging ; Male ; Propofol ; pharmacology ; Stress, Mechanical ; Young Adult

The present study aimed to investigate the effect of proto-oncogene c-src on the viability of rat spermatogonial stem cells from 9 day-old rat in vitro. MTT method was used to observe the viability of the spermatogonial stem cells treated with antisense c-src oligodeoxynucleotides (ODNs) in vitro; RT-PCR was utilized to observe the expression of c-src mRNA and Western blot was used to observe the protein expressions of pp60c-src and phosphorylated signal transducer and activator of transcription-3 (p-STAT3). Compared with that in control group, the viability of spermatogonial stem cells decreased by 8.1% (P<0.05) and the expression of c-src mRNA decreased significantly after treatment with 10 μmol/L antisense c-src ODNs for 12 h. Compared with that in the control group, the protein expressions of pp60c-src and p-STAT3 decreased by 33.8% and 45.3% (both P<0.01), respectively, in the spermatogonial stem cells after being transfected with antisense c-src ODNs. The results suggest that proto-oncogene c-src regulates the viability of rat spermatogonial stem cells through p-STAT3.
Animals ; Cells, Cultured ; Genes, src ; Male ; Phosphorylation ; Proto-Oncogene Proteins pp60(c-src) ; metabolism ; RNA, Messenger ; Rats ; STAT3 Transcription Factor ; metabolism ; Spermatogonia ; cytology ; metabolism ; Stem Cells ; cytology ; metabolism ; Transfection

Aged ; Femur ; Head and Neck Neoplasms ; surgery ; Humans ; Male ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; Surgical Flaps

Soy isoflavones have been reported to be natural chemopreventive in several types of human cancer. Daidzein and genistein are two main components of soy isoflavones. In our previous study, they were shown to be anti-proliferative and induce cell cycle arrest at S phase of SHZ-88 rat breast cancer cells. We hypothesized that soy isoflavones might exert its anticancer effect by activating cAMP/PKA pathway. The present study was designed to analyze the effect of soy isoflavones on the cAMP/PKA pathway in SHZ-88 cells. Daidzein and genistein were dissolved in DMSO. Cells were treated with 50 mug/ml daidzein and 15 mug/ml genistein, respectively, and with only equal DMSO in the culture medium as control. The cellular cAMP content was tested by radioimmunoassay (RIA). The activity of adenylate cyclase (AC), phosphodiesterase (PDE) and PKA were measured by RIA and (gamma-(32)P) ATP incorporation. Reverse transcript-polymerase chain reaction (RT-PCR) was used to analyze the expression of cAMP response element binding protein (CREB) mRNA of the cells. The results showed that the concentration of cAMP in the cells treated with 50 mug/ml daidzein and 15 mug/ml genistein was significantly increased by 9.5%and 11.0%, respectively, 5 min later (P<0.05), then increased by 31.0%and 40.3%, respectively, 10 min later (P<0.01), compared with that of the control group cells. The activity of AC was not affected during the course of experiment, but that of PDE was decreased to 71.8%and 71.6%, respectively, in the control group 5 min later (P<0.05). The PKA activity was increased to 125.8%and 122.3%, respectively, in the control group 20 min after the cells were treated with daidzein and genistein (P<0.05), and kept at high level till 40 min after treatment. CREB mRNA of the cells treated with daidzein and genistein was increased by 31.6%and 51.1%, respectively, 3 h later (P<0.05), then began to decrease 6 h after treatment. The current study suggests that soy isoflavones activate the cAMP/PKA pathway in SHZ-88 rat breast cancer cells by inhibiting the activity of phosphodiesterase.

This study was purposed to comparatively analyze the cytogenetic characteristics between 566 cases of adult acute lymphoblastic leukemia (aALL) and 586 cases of childhood acute lymphoblastic leukemia (cALL). The cytogenetic analysis of all the patients was performed, and the FISH detection for partial patients was carried out. The result showed that the difference of chromosome abnormality between cALL and aALL was statistically significant. The percentage of abnormal karyotypes in aALL was 62.0%, including mainly t(9;22)(q34;q11), hypodiploidy, hyperdiploidy (47 - 50), abn(6q), abn(9p) and -7, most of which conferring an unfavorable prognosis. The percentage of abnormal karyotypes in cALL was 39.2%, composed mainly of high hyperdiploidy, hypodiploidy, TEL/AML1(+), +8, hyperdiploidy (47 - 50) and +21, etc, most of which conferring a favorable prognosis. The incidences of abnormal karyotypes, total hypodiploidy, total hyperdiploidy (47 - 50), t(9;22)(q34;q11), -7, abn(7q), abn(14q32) and +Ph in aALL were significantly higher than those of cALL (p < 0.05), whereas the incidences of normal karyotype (N), high hyperdiploidy, +8, +21*2 and TEL/AML1(+) in cALL were significantly higher than those of aALL (p < 0.05). 20.5% of aALL were Ph+ aALL, with 63.8% of which being with additional abnormalities, composed mainly of +Ph, -7, i (9q+), 9p-, +8, +21, +X, 6q-, abn(14q32) and +14. In contrast, only 4.4% of cALL were Ph+ aALL, with 42.3% of which being with additional abnormalities, including mainly abn(9p), abn(7p), -7, 17p- and +21. It is concluded that almost every chromosome is involved in the numerical and structural abnormalities and complex karyotypes are common. The significant difference of chromosome abnormality exists between aALL and cALL.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Chromosome Aberrations ; Cytogenetic Analysis ; Female ; Humans ; Infant ; Infant, Newborn ; Karyotyping ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Sample Size ; Young Adult

Aim To prepare hyaluronic acid nanoparti-cles(Ade/GA-HA) using glycyrrhetinic acid modified hyaluronic acid as the carrier and adenine as a model drug, and analyze their physicochemical property and proliferation effect on Bel-7402 cells. Methods Gly-cyrrhetinic acid and hyaluronic acid were combined by chemical cross-linking method, dialysis and freeze-dr-ying,based on which Ade/GA-HA was prepared using ultrasonic method, and the particle size and Zeta po-tential were determined by Malvern laser particle analy-zer,and the morphology was observed by transmission electron microscopy, and the absorbance was deter-mined by ultraviolet-visible spectrophotometer, high performance liquid chromatograph and microplate read-er to caculate drug load, encapsulation efficiency and in vitro release. MTT assays were utilized to determine the proliferation of nanoparticles treated Bel-7402 cells. Results GA-HA nanoparticles had spherical shape with a good dispersion, at diameters of 398.1 nm, of which Zeta potential was - 34.2 mV, and presented good short term stability. The drug load and encapsulation efficiency of Ade/GA-HA nanoparticles were (22.5 ± 5.8)% and (87.27 ± 0.33) %, re-spectively. Burst release was observed in Ade/GA-HA nanoparticles within 4 h, while controlled release 4 h later. Compared with free adenine,Ade/GA-HA nano-particles had a stronger inhibitory effect on cell prolif-eration with statistically significant difference. Conclu-sion GA-HA nanoparticles has excellent physico-chemical properties and meet the design requirement.

Objective:To analyze the effectiveness and safety of the treatment strategies for vascular restenosis after stent implantation in atherosclerosis obliterans (ASO) .Methods:The clinical data of 5 cases who had received drug‐perfused balloon from January to July in 2016 and 15 cases who had received femoral artery retrograde endarterectomy from June 2012 to July 2016 after presenting reocclusion or restenosis atherosclerosis lesions were reviewed retrospectively .The effects of surgery and complications in follow‐up period were analyzed .The effectiveness ,availability and safety of the above two methods were assessed .Results:The 20 patients had acquired an adequate blood perfusion in their distal limbs and got warmer on their feet after underwent drug‐perfused balloon and stent implantation or femoral artery retrograde endarterectomy .In addition ,they could have good palpitation in dorsal artery of feet and have better feelings on account of relieving pain .In the follow‐up ,no restenosis case had been found among them .Conclusions:The application of the stent angioplasty after using drug‐perfused balloon and femoral artery retrograde endarterectomy on vascular restenosis after stent implantation in atherosclerosis lesions proved to be effective and safe ,greatly reducing the restenosis or reocclusion frequency .