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OBJECTIVES@#This study aims to investigate the incidence and severity of obstructive sleep apnea (OSA) in cleft patients with velopharyngeal insufficiency (VPI) after pharyngeal flap surgery (PFS) and explore the influence of operation age.@*METHODS@#A retrospective study was conducted in 82 cleft patients after PFS. The patients were divided into two groups according to their age at the time of surgery. The incidence and severity of OSA were assessed at least 1.2 years (mean 6.0 years) postoperatively by polysomnography (PSG).@*RESULTS@#The incidence rates of OSA were 20% in the adult group and 31% in the child group. No significant difference was found between the two groups (@*CONCLUSIONS@#Some patients still have OSA average of 6.0 years after PFS, and operation ageis unrelated to the incidence and severity of OSA.
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Adulte , Enfant , Humains , Pharynx , Polysomnographie , Études rétrospectives , Syndrome d'apnées obstructives du sommeil/épidémiologie , Insuffisance vélopharyngée/étiologieRésumé
Objective To isolate and identify the proteins that interact with cardiac troponin I (cTnI) in primary mouse cardiomyocytes,and to analyze their biological processes and signaling pathways by use of High throughput proteomics and bioinformatics techniques.Methods The hearts of C57 neonatal mice were used to prepare the primary cardiomyocytes.The cTnI binding proteins were extracted from the whole cell protein by co-immunoprecipitation,and the proteins were analyzed and identified by mass spectrometry.Furthermore,the physicochemical properties,biological processes and signaling pathways of cTnI interacting proteins were predicted by bioinformatics tools.Results A total of 262 proteins were identified by mass spectrometry,cTnI binding proteins were involved in 14 biological processes and 33 KEGG biological pathways (P<0.05).Conclusion In mouse cardiomyocytes,262 kinds of proteins may interact with cTnI,and participate in regulation of calcium ion influx and PI3K-Akt signaling pathways.
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Objective: To analyze associations of MRI-lesions and clinical features with disability in patients with multiple sclerosis (MS) in Shanghai, China. Methods: We studied patients with MS, identified from a survey in Shanghai, whose sites of lesions in the CNS was based on the MRI examinations. Associations between MRI-lesions, various clinical variables and the severity of disability were analyzed with univariate and multivariate logistic regression analysis. Results: There were 210 patients in this study. The disability of the patients with lesions confined to the spinal cord was significantly more severe than those with lesions in the brain (p < 0.008). Current age (OR: 1.041, 95% CI: 1.007~1.077), MS duration (OR: 1.082, 95% CI: 1.011~1.159) and MRI-lesions in the spinal cord (OR: 2.441, 95% CI: 1.039~5.737) were significantly associated with severity of disability on multivariate logistic regression analysis. Conclusion: MRI-lesions in the spinal cord, older age, a longer MS duration were significantly associated with a more severe disability in this MS study in Shanghai China.
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<p><b>BACKGROUND</b>Glucocorticoid receptor (GR) is believed to be a major factor in brain maturation and in modulation of a series of brain activity. Hippocampal neurons are abundant in glucocorticoid receptor, and there is significant change in GR expression under certain pathological state. Epilepsy is a special pathological state of the central nervous system. This study aimed to explore the role of GR in epilepsy by observing the change and functions of GR in hippocampus with a basolateral amygdale-electrical kindled rat epilepsy model.</p><p><b>METHODS</b>Firstly, we established the basolateral amygdale-electrical kindled rat epilepsy model. Then GR mRNA expression in the hippocampus was assayed by semi-quantitative reverse transcription-PCR in this experiment. In addition, the processes of epileptic seizures were observed and electroencephalograms were recorded. One-way analysis of variance (ANOVA) was employed for comparing means of multiple groups, followed Fisher's least significant difference (LSD) for paired comparison.</p><p><b>RESULTS</b>The rats were successfully kindled after an average of (13.50 ± 3.99) times electrical stimulation, in which it was showed that GR mRNA expression reduced obviously as compared with the control group and the sham groups (P < 0.001). The down-regulation of GR mRNA expression was abated or reversed by some anti-epilepsy drugs (P < 0.001 compared with the epilepsy group), accompanied by attenuation of seizures and improvement of electroencephalograms.</p><p><b>CONCLUSIONS</b>Down-regulation of hippocampal GR mRNA expression may be related to the kindling. Anti-epilepsy drugs exposure can retard this change.</p>
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Animaux , Mâle , Rats , Amygdale (système limbique) , Métabolisme , Épilepsie , Génétique , Embrasement , Génétique , Rat Sprague-Dawley , Récepteurs aux glucocorticoïdes , Génétique , RT-PCRRésumé
<p><b>OBJECTIVE</b>To investigate the efficacy of nucleosides as a prophylactic agent against reactivation of hepatitis B virus (HBV) in HBsAg-positive patients with non-hepatic tumors after chemotherapy.</p><p><b>METHODS</b>Fifty-eight patients with non-hepatic tumors were divided into prevention group and control group. The patients of prevention group received nucleosides as a prophylactic agent before chemotherapy and were compared with the control ones about the clinical manifestation of HBV reactivation. Then, the patients of the control group were divided into three groups according to antiviral drugs, use or not and time of the use. The patients having HBV reactivation but never received nucleosides were included in the group A, the patients receiving nucleosides after having HBV reactivation were divided into the group B, and the patients receiving nucleosides before HBV reactivation were divided into the group C. The progression, prognosis and curative effect among the three groups were compared.</p><p><b>RESULTS</b>The rate of HBV reactivation, incidence of severe hepatitis, mortality rate of the control group (61.1%, 27.8%, 16.7%) were significantly higher than those of the prevention group (13.6%, 0, 0), and liver dysfunction was more serious than that in the prevention group. In the control group, all the 5 patients of group A died of liver failure. Of the 13 patients in the group B, 4 cases suffered from severe hepatitis and 1 of them died of the disease. Of the 18 patients in the group C, 4 cases suffered from HBV reactivation, but the clinical manifestation was milder than that of the group B.</p><p><b>CONCLUSION</b>Nucleosides can be used as a prophylactic measure to prevent HBV reactivation. If chemotherapy had begun, the use of nucleosides may reduce the risk of HBV reactivation. Even if patients had suffered from HBV reactivation, the use of nucleosides may still help the recovery of liver function and improve prognosis.</p>
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Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Antinéoplasiques , Utilisations thérapeutiques , Antiviraux , Utilisations thérapeutiques , Tumeurs du sein , Sang , Traitement médicamenteux , Études de suivi , Guanine , Utilisations thérapeutiques , Hépatite B , Traitement médicamenteux , Antigènes de surface du virus de l'hépatite B , Sang , Virus de l'hépatite B , Physiologie , Lamivudine , Utilisations thérapeutiques , Tumeurs du poumon , Sang , Traitement médicamenteux , Lymphomes , Sang , Traitement médicamenteux , Nucléosides , Utilisations thérapeutiques , Pyrimidinones , Utilisations thérapeutiques , Études rétrospectives , Thymidine , Activation viraleRésumé
Objective To assess the impact on caretaker who looked after patients with Parkinson's disease(PD) and to identify the main factors related to their burden.Methods 115 consecutive pairs of PD patients and their caretakers were included.Caregiver Burden Inventory (CBI) was used to assess the burden of PD on the caretakers.Patients were evaluated by neurologists using the United Parkinson's Disease Rating Scale(UPDRS),the Hoehn and Yahr Scale(H-Y Scale),the Activity of Daily Liring Scale(ADL),the Parkinson's Disease Quesnonnaire(PDQ-39),the Hamilton Depression Rating Scale(HAMD),the Hamilton Anxiety Rating Scale(HAMA),the Montreal Cognitive Assessment(MoCA)and the Mini-mental State Examination(MMSE).Multiple linear stepwise regression models were fired to ascertain the factors linked to the CBI.Results Based on multiple linear stepwise regression analysis,ADL(β=-0.813,t=-6.265,P=0.000)and PDQ-39(β=0.285,t=4.256,P=0.000)of patients and the age ofcaretakers(β=0.327,t=3.107,P=0.002)proved to be the main predictors of CBI.Conclusion Many factors might comprehensively affct the burden of PD on caretakers of the patients.Attention needs to be given to the early identification of factors that generating stress on 1iveretakers in order to improve their quality of life.
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<p><b>OBJECTIVE</b>To analyze the characteristic of bacterial infections, and the relationship between antibiotics treatment and bacterial infections after liver transplantation, and to prevent antibiotic-resistant bacterial infections.</p><p><b>METHODS</b>86 liver transplant recipients were retrospected. Different indexes including limited daily dose, the frequency of medication, drug use index were used to evaluate the rationality of the use of antibiotics, three-dimensional test was used to explore extended-spectrum beta-lactamase and AmpC enzyme of Gram-negative bacteria.</p><p><b>RESULTS</b>The major pathogens of infection after liver transplantation were Enterococcus faecalis, Enterobacter cloacae, fungi and E. coli. Pre-operative antibiotic utilization rate was 83.7%, it was mainly a single use of antibiotics; After- operative antibiotic usage was 100.0%, it was mainly joint use of two or three antibiotics; The top 3 antibiotics used were cephalosporins, the combined enzyme inhibitors and penicillin. Antibiotics with drug utilization index (DUI) more than 1.1 included ampicillin and Lalin proxy. 43.3% and 31.8% of Gram -Negative bacteria produced ESBLs and AmpC, respectively, while 21.3% Gram -Negative bacteria produced two enzymes.</p><p><b>CONCLUSION</b>There is high incidence of bacterial infections after liver transplantation. The use of antibiotics is high dose, high-frequency and reasonable; High resistance of bacterial infections was prone to develop and the prevention of the high resistance of bacterial infections is very important.</p>
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Adolescent , Adulte , Sujet âgé , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Nourrisson , Mâle , Adulte d'âge moyen , Jeune adulte , Antibactériens , Utilisations thérapeutiques , Infections bactériennes , Traitement médicamenteux , Microbiologie , Résistance bactérienne aux médicaments , Bactéries à Gram négatif , Bactéries à Gram positif , Transplantation hépatique , Méthodes , Tests de sensibilité microbienne , Complications postopératoires , Traitement médicamenteux , Épidémiologie , Microbiologie , Études rétrospectives , bêta-LactamasesRésumé
Objective To investigate the effects of subthalamic nucleus (STN)-deep brain stimulation (DBS) on expression of dopamine and adenosine 3'5'-monophosphate-regulated phosphor-protein(DARPP-32) and its phosphorylated proteins in corpus striatum of rat models with levodopa-induced dyskinesia. Methods The rat models of levodopa-induced dyskinesia were set up and were given STN-DBS (stimulation group). The expression of DARPP-32 and its phosphorylated proteins in corpus striatum (damage side and normal side) were detected and compared with sham-stimulation group and sham-operation group. Results There was no significant difference in the expression of DARPP-32 total protein in corpus striatum of rats with dyskinesia among three groups (P>0.05). The expression of Phosphor-Thr34-DARPP-32 protein in the damage side of corpus striatum in stimulation group was significantly lower than that in sham-stimulation group and sham-operation group (P<0.05), while the expression of Phosphor-Thr75-DARPP-32 protein in the damage side of corpus striatum in stimulation group was significantly higher than that in sham-stimulation group and sham-operation group (P<0.05). Conclusion DARPP-32 and its phosphorylated proteins play an important role in the pathogenesis of levodopa-induced dyskinesia.
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Objective To investigate the expression pattern of tropomyosin receptor kinase(Trk)after focal cerebral ischemia in rat,and to explore the relationship between ischemia and the pattern of Trk expression. Methods(The model) of focal cerebral ischemia was built by middle cerebral artery occlusion.Immunocytochemistry staining was used to observe the dynamic changes of Trk expression at different time of acute stage of ischemia,and the patterns at different regions of the striate and hippocampal were detected. Results Trk immuno-positive neurons widely expressed in the normal brain.The number of Trk immuno-positive neurons was decreased abruptly in the necrosis core of the focal cerebral of ischemia,while increased obviously in the penumbra region and the DG area after 6 h of occlusion(P
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Objective To explore the effects of chronic levodopa treatment on characteristics of N-methyl-D-aspartate(NMDA) receptor subunit 1(NR1) on the neurons of striatum in rat models of Parkinsonism related motor complications.Methods Rat models(n=25)of Parkinsonism related motor complications were established and were randomly divided into solvent treatment group(n=5,intraperitoneal injection with vitamin C),levodopa chronic treatment group(n=10,intraperitoneal injection with levodopa for 23 d) and MK-801 treatment group(n=10,intraperitoneal injection with MK-801 on d 23 after intraperitoneal injection with levodopa for 22 d).Another 5 rats were served as controls(sham-operation group,n=5).Locomotion changes of rats in MK-801 treatment group were recorded,and NR1 phosphorylation in the other three groups was detected by Western blotting. Results After chronic treatment with levodopa methylester for 1,8,15 and 22 d,rats in MK-801 treatment group displayed shortened rotational duration and increased peak rotation.Compared with d 22,MK-801 both prolonged rotational duration and reduced peak rotation(P0.05).The expression of NR1,phosphorylated NR1S890,NR1S896 and NR1S897 in striatal membranes in levodopa chronic treatment group was increased compared with that of solvent treatment group(P
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Objective To explore the relationship between predictable ocular motor control and cognitive function in Parkinson's disease(PD). Methods Videonystagmography was used to examine 24 patients with idiopathic PD(PD group) and 24 healthy controls(control group) on predictable ocular motor control.The accuracies of saccade were compared between two groups.The correlation among accuracy for predictive saccade(latency
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Sleep disorders are commonly occurred among patients with Parkinson's disease,such as difficulties in the initiation of sleep,fragmented sleep,sleep behavior disorder and excessive daytime sleepiness.The mechanism of sleep disorders associated with Parkinson's disease is not clear,which may be associated with the injury of brain stem,nuclei of median raphe,nuclei fasciculi solitarii,thalamencephalon and the changes of neurotransmitters as dopamine,hypocretin(orexin) and melatonin.This article gives an overview of the mechanism of sleep disorders associated with Parkinson's disease.
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Neurotrophic factor activates signal pathways of intracellular phosphoinositide 3-kinase and extracellular signal-regulated kinase after acting on Trk receptor tyrosine kinase.It promotes the survival and differentiation of neurons.The development of small molecule Trk agonists of non-peptides and neurotrophic factor simulants can avoid a number of shortcomings of neurotrophic factors while agitating trk receptor signal transduction.It may provide a novel therapeutic approach for the treatment of nervous system diseases.
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Objective To explore the mechanism of deep brain stimulation(DBS)therapy to Parkinson's disease(PD).Methods We produced hemi-parkinsonian rat model with stereotaxically injecting 6-OHDA to right medial forebrain bundle(MFB)and stimulated ipsilateral subthalamu nucleus (STN)with platinum electrodes chronically to investigate the influence of DBS to the expression of Calbindin-28,synaptophysin and tyrosine dioxydase(TH)in Striatum by Western blot.In addition,slices of bilateral PD rats after DBS were stained to observe the expression of Calbindin-28 and synaptophysin in substantia nigra by Immunohistochemistry.Results High frequency stimulation impaired the rotational frequency 31% of unilateral PD rats triggered by apomophine;Long-term DBS increased the expression of TH in innocent striatum of unilateral PD rats 78.6%?9.5%,since the ipsilateral striatum(lesion side) was TH depleted by 6-OHDA insults;Calbindin-28 expression in ipsilateral striatum of hemi-PD rats raised up 75.4%?15.0% and long-term DBS reduced the effect by 43.0%?7.1%,meanwhile Calbindin-28 positive neurons in substantia nigra compacta in sham,PD and DBS rats were 74.5?10.2,75.7?15.6, 33.1?7.8.However,Synaptophysin expression in substantia nigra and striatum kept stable even after long- term DBS.Conclusions Consistent to the treatment to PD patients,DBS to STN alleviated the motor disorder of PD rats,the treatment might be based on regulating the expression of Calbindin-28 and TH.
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<p><b>AIM</b>To study the metabolic kinetics of MN9202 in Beagle dog liver microsome.</p><p><b>METHODS</b>Beagle dog liver microsomes were prepared by using ultracentrifuge method. After incubating 0.4 micromol x L(-1) MN9202 with 1 g x L(-1) microsomes for 30 min at 37 degrees C, the reaction was terminated by adding 0.5 mL alkalization. The RP-HPLC was used to determine the drug in the incubation mixture. The Michaelis-Menten parameters Km, and Vmax in Beagle dog liver microsomes were initially estimated by analyzing Lineweave-Brurk plot. Various selective CYP inhibitors were used to investigate their inhibitory effect on the metabolism of MN9202.</p><p><b>RESULTS</b>The Km, Vmax and CLint of MN9202 were (22.6 +/- 8.0) micromol x L(-1), (0.54 +/- 0.17) micromol x g(-1) x min(-1) and (0.0242 +/- 0.0009) L x g(-1) x min(-1), respectively. The metabolism of MN9202 was significantly inhibited by ketoconazole (Ket) and troleandomycin (Tro) in Beagle dog liver microsomes. Tranylcypromine (Tra) could inhibit the metabolism of drug as well. While other inhibitors showed little inhibitory effect on the metabolism of MN9202.</p><p><b>CONCLUSION</b>It was shown that CYP3A and CYP2C19 were involved in MN9202 metabolism. The inhibitors of human CYP3A and CYP2C19 may have potential interaction with MN9202, and this can reduce the metabolism rate and increase the toxicity of MN9202.</p>
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Animaux , Chiens , Aryl hydrocarbon hydroxylases , Inhibiteurs des canaux calciques , Métabolisme , Pharmacocinétique , Cytochrome P-450 CYP2C19 , Inhibiteurs du cytochrome P-450 CYP3A , Dihydropyridines , Métabolisme , Pharmacocinétique , Kétoconazole , Pharmacologie , Microsomes du foie , Métabolisme , Mixed function oxygenases , Nitrobenzènes , Métabolisme , Pharmacocinétique , Tranylcypromine , Pharmacologie , Troléandomycine , PharmacologieRésumé
Objective To explore the relationship between the genesis of dyskinesia and the degree of substantia nigra lesion in Parkinson disease(PD).Methods The hemi-parkinsonian rat model was established by injecting 6-OHDA stereotaxically to right medial forebrain bundle(MFB). Then the hemi-parkinsonian rat was injected intraperitoneally with levodopa methylester(25 mg?kg~(-1)?d~(-1),twice a day)for 21 days,the abnormal involuntary movements were estimated.After being sacrificed,the midbrain was removed,and the injured degree of dopaminergic neurons at substantia nigra was observed by tyrosine hydroxylase immunohistochemistry staining.The relationship between the abnormal involuntary movement scores and dopaminergic neurons loss at substantia nigra was evaluated by sigmoid equation analysis by using Excel software.Results The apomorphine-induced rotation rate above 7 r/min was found in 10 of 25 rats,those rats were regarded as successful hemi-parkinsonian model rats.After the treatment with levodopa methylester,8 of 10 rats displayed abnormal involuntary movements,including stereotype and contralateral rotation,the types of movements varied.Abnormal involuntary movements were appeared in the rats with dopaminergic neurons loss above 90%.The positive relationship was observed between the degree of lesion in substantia nigra and the severity of abnormal involuntary movements.Conclusions The severe loss of dopaminergic neurons at substantia nigra probably plays a role in the development of levodopa-induced dyskinesia in patient with Parkinson disease.
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Objective To investigate cellular and behavioural effects of 5-HT1A receptor agonist 8- OH-DPAT in a rat model of levodopa-induced motor complications.Methods The hemi-parkinsonian rat model was produced by stereotaxically injecting 6-OHDA to right medial forebrain bundle(MFB).Two sets of experiments were performed.First,rats were intrapefitoneally treated with levodopa 50 mg/kg plus benserazide 12.5 mg/kg twice a day for 22 days.On day 23,rats intraperitoneally received either 8-OH- DPAT(1 mg/kg)or 8-OH-DPAT plus WAY-100635(0.1 mg/kg)or dissolvent with each levodopa dose as controls.In the second set,rats were intraperitoneally treated either with levodopa(50 mg/kg)plus 8-OH- DPAT(1 mg/kg)or levodopa 50 mg/kg plus dissolvent,administered twice daily for 22 consecutive days. Rotational duration and frequency of off period were estimated.After sacrificed,subcellualr distribution of GluR1 and GluR1Ser845 phosphorylation was observed by Western blot.Results 8-OH-DPAT,reversing the shortened rotational duration induced by levodopa,prolonged the rotational duration by 27.8%?6.1% and reduced the frequency of failures to levodopa by 7.2%?1.7%.Co-administration of WAY-100635,a 5-HT1A receptor antagonist,with 8-OH-DPAT eliminated the effect of 8-OH-DPAT on motor complications, indicating that the observed 8-OH-DPAT responses were probably mediated via the 5-HT1A autoreceptor. Moreover,8-OH-DPAT could regulate subcellular distribution of GluR1 and reduce hyperphosphorylation of GluR1 Ser845 by 22.1%?3.5%,which was closely associated with levodopa-induced motor complications. Conclusions These results suggest that pharmaceuticals stimulating 5-HT1A receptors could be useful in the treatment and prevention of the motor complications in parkinsonian patients.
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Objective To investigate the effect of neutral amino acid on preventing Parkinson disease.Methods Mice were injected with L-Valine,L-Pheylalanine,D-Valine or L-Lysine before or after paraquat administration,by which prakinsonian mouse model was constructed.The paraquat immunoreactivity was observed within nigral cell bodies.Then neurodegeneration and ?-synuclein aggregation were observed by immunohistochemistry and Western blot.Results Paraquat immunoreactivity was abolished by the administration of L-Valine,L-Pheylalanine before paraquat exposure.Pre-treatment with these two amino acids also protected the paraquat-induced loss of nigrostriatal dopaminergic cells and formation of thioflavine S-positive aggregates.In contrast, paraquat-induced toxicity was unaffected if animals were injected with these two amino acids after paraquat exposure or pre-treated with D-Valine or L-Lysine.Conclusions L-type neutral amino acids such as L Valine and L-Pheylalanine can prevent paraquat-induced neurodegeneration and a synuclein pathology through a competitive inhibition mechanism with stereospecificity in the central nervous system (CNS).Neutral amino acid could protect the dopaminergic neuron in substantia nigra and may prevent Parkinson disease.