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

In this study, ultra performance liquid chromatography-quadrupole-time of flight mass spectrometer-MS^E (UPLC-Q-TOF-MS^E) combined with UNIFI analysis platform was used to rapidly analyze and identify the metabolites of hederagenins 3-O-α-L-rhamnosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-α-L-arabopyranoside (Pulsatilla saponin D) and oleanolic acid 3-O-α-L-rhamnosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-α-L-arabopyranoside (Pulsatilla saponin B₇) and hederagenins 3-O-α-L-rhamnosyl-(1→2)-α-L-arabopyranoside (Pulsatilla saponin BD) in plasma and colonic tissue of normal and ulcerative colitis (UC) rats. The database and analysis methods were established based on the precise molecular weight of compounds, retention time, neutral loss and reported data, and then the final data were obtained by comparing with the blank control group, combining with the deviation and the cracking rule of the compound. The results showed that the glucoses, hydroxylation and dehydroxylation, methylation and demethylation, dehydrogenation, decarboxylation and hydrolysis of saponin D, B₇ and BD occurred in the plasma and colon tissues of normal and UC model rats. This study will clarify the metabolic transformation of Pulsatilla saponins D, B₇ and BD in rats, determine the prototype components and their metabolites that enter the body, and whether colon injury will affect their metabolism in vivo, so as to explore the possible anti-colitis effective components in the prototype or metabolites of Pulsatilla saponins D, B₇ and BD. This experiment was approved by Animal Ethics Committee of Jiangxi Science and Technology Normal University (approval number: Y202227).

Acclimatization ; Altitude ; Electroencephalography ; Humans

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

OBJECTIVETo detect the underlying genetic defect in two Chinese families with hereditary multiple exostoses and provide genetic counseling.

METHODSPotential mutations in EXT1 and EXT2 genes in the probands were detected by direct sequencing of PCR-amplified exons. Suspected mutations were verified in all available family members and 200 unrelated healthy controls.

RESULTSA heterozygous frameshift mutation c.346_356delinsTAT in exon 1 of EXT1 and a heterozygous deletion mutation c.2009-2012del(TCAA) in exon 10 of EXT1 were respectively detected in affected members from the two families. The same mutations were not detected in unaffected members and 200 unrelated healthy controls. No mutations in EXT2 were detected in the two families.

CONCLUSIONTwo novel mutations of EXT1 have been detected in association with hereditary multiple exostoses in two Chinese families. Above results have provided a basis for genetic counseling for the two families and expanded the spectrum of EXT1 mutations.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; DNA Mutational Analysis ; methods ; Exostoses, Multiple Hereditary ; enzymology ; genetics ; Female ; Heterozygote ; Humans ; Male ; Middle Aged ; N-Acetylglucosaminyltransferases ; genetics ; Pedigree ; Sequence Deletion ; Young Adult

OBJECTIVETo study the influence of cow's milk protein allergy (CMPA) on the diagnosis of functional gastrointestinal diseases (FGID) based on the Rome IV standard in infants and young children.

METHODSA total of 84 children aged 1 month to 3 years who were diagnosed with CMPA were enrolled as the case group, and 84 infants and young children who underwent physical examination and had no CMPA were enrolled as the control group. The pediatricians specializing in gastroenterology asked parents using a questionnaire for the diagnosis of FGID based on the Rome IV standard to assess clinical symptoms and to diagnose FGID.

RESULTSThe case group had a significantly higher incidence rate of a family history of allergies than the control group (P<0.05). In the case group, 38 (45%) met the Rome IV standard for the diagnosis of FGID, while in the control group, 13 (15%) met this standard (P<0.05). According to the Rome IV standard for FGID, the case group had significantly higher diagnostic rates of reflex, functional diarrhea, difficult defecation, and functional constipation than the control group (P<0.05). The children who were diagnosed with FIGD in the control group were given conventional treatment, and those in the case group were asked to avoid the intake of cow's milk protein in addition to the conventional treatment. After 3 months of treatment, the case group had a significantly higher response rate to the treatment than the control group (P<0.05).

CONCLUSIONSIn infants and young children, CMPA has great influence on the diagnosis of FGID based on the Rome IV standard. The possibility of CMPA should be considered during the diagnosis of FGID.

Adolescent ; Adult ; Child ; Female ; Hemostasis, Surgical ; methods ; Humans ; Male ; Middle Aged ; Subclavian Artery ; injuries ; Subclavian Vein ; injuries ; Vascular Surgical Procedures ; methods ; Wounds and Injuries ; surgery

Objective To explore the clinical value of double-balloon enterocopy (DBE) in diagnosis of small intestinal diseases. Methods The clinical and endoscope image data of 231 patients with suspected small bowel disease who underwent DBE from January 2008 to May 2016 were analyzed. Result 231 patients received 257 times of DBE examination, 112 of them were performed by oral and 93 by anal route, 26 patients were underwent by both approaches. The detection rate of intestine diseases was 64.9% (150/231), include 33 cases (14.3%) of nonspecific enteritis, 27 cases (11.7%) of crohn's disease, 19 cases (8.2%) of ulcer, 13 cases (5.6%) of intestinal vascular malformation, 12 cases (5.2%) of small intestinal stromal tumor. The lesion detection rate in obscure abdominal pain and obscure gastrointestinal bleeding were 59.6% (62/104) and 67.0% (63/94). In all patients, there were 1 case of small bowel perforation, the remaining patients had no serious complications such as bleeding and perforation. Conclusion The positive detection rate of double-balloon enteroscopy examination is high, and the double-balloon enteroscopy examination is relatively safe. So, double-balloon enterscopy examination has high diagnostic value for detecting small intestine diseases.

OBJECTIVETo explore the intrinsic connection between activation of classical nuclear factor-κB (NF-κB) pathway and gefitinib resistance in human lung adenocarcinoma H1650 cells.

METHODSHuman lung adenocarcinoma H1650 cells were exposed to gefitinib continuously for 60 days to obtain resistant H1650 cells. The expressions of P-IκBα, P-p50 and P-p65 in the cytoplasm or nuclei were detected using Western blotting in human lung adenocarcinoma HCC827 cells, parental H1650 cells and gefitinib-resistant H1650 cells. The effects of gefitinib alone or in combination with PDTC on the survival rate and expressions of NF-κB P-p50 and P-p65 were compared among the 3 cell lines.

RESULTSGefitinib-resistant H1650 cells showed increased cytoplasmic and nuclear P-IκBα expressions. The expressions of P-p50 and P-p65 differed significantly among the 3 cell line, decreasing in the order of resistant H1650 cells, parental H1650 cells, and gefitinib sensitive HCC827 cell lines (P<0.05 or 0.01). Treatment with gefitinib alone resulted in a significantly lower cell inhibition rate in resistant H1650 cells than in the parental H1650 cells (P<0.05) and HCC827 cells (P<0.01). The resistant H1650 cells had a significantly higher expression of P-p50 and P-p65 than other two cell lines (P<0.05). In both the resistant and parental H1650 cells, gefitinib significantly lowered P-p50 and P-p65 expressions (P<0.05 or 0.01), and the combined treatment with gefitinib and PDTC significantly decreased the cell survival rate and further lowered the cytoplasmic and nuclear expressions of P-p50 and P-p65 (P<0.01 or 0.01).

CONCLUSIONThe activation of classical NF-κB pathway is a key factor contributing to transformation of the parental H1650 cells into gefitinib-resistant cells. Gefitinib combined with PDTC can inhibit P-IκBα production and NF-κB P-p50 and P-p65 activation to suppress the survival of residual H1650 cells and the generation of gefitinib-resistant cells.