Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Objective:To explore the incidence and severity of esophageal clearance impairment in stroke survivors with dysphagia, the clinical characteristics of patients with abnormal esophageal clearance, and their relationship with swallowing physiology, penetration and aspiration.Methods:Clinical data were collected describing 174 stroke survivors whose swallowing had been studied videofluoroscopically. In each selected case there was a good anterior-posterior view of esophageal clearance. Their anterior-posterior and lateral imaging results while swallowing 5ml of high-consistency food were analyzed. The esophageal clearance item of the modified barium swallow impairment profile was then used to rate each subject′s esophageal clearance and each physiological component of swallowing in the oral and pharyngeal phases. The Rosenbek penetration aspiration scale was employed evaluate the safety of their swallowing.Results:Seventy of the patients (40.2%) displayed abnormal esophageal clearance, and more than half of the 70 (43 patients, 24.7%) showed mid- to distal esophageal retention. Those with abnormal esophageal clearance had a higher average age and more severe overall impairment in the pharyngeal phase of swallowing. Esophageal clearance was not, however, significantly correlated with swallowing physiology in the oral phase or with penetration or aspiration grade. There were, however, significant positive correlations with laryngeal elevation, anterior hyoid excursion, pharyngeal stripping waves, pharynx contraction, upper esophageal sphincter opening, tongue base retraction and pharyx residue.Conclusion:Stroke survivors with dysphagia may display abnormal esophageal clearance. The risk is closely related to age and the severity of the dysphagia. Abnormal physiology during the pharyngeal phase of swallowing and reduced pharyngeal stripping may predict abnormal esophageal clearance. Swallowing assessment can be made more comprehensiveness and systematic by incorporating anterior-posterior videography in routine barium swallowing studies.

Objective To study tirofiban intravenous injection,coronary artery injection of the two different methods in acute ST segment elevation myocardial infarction,the application of emergency PCI.Methods Patients underwent emergency PCI with acute ST segment elevation myocardial infarction as the research subjects,a total of 108 cases,the patients were randomly divided into the observation group and control group,54 patients in each group. In the observation group,the first dose of tirofiban was injected into the coronary artery.The control group was treated by intravenous injection.The results of the two groups were compared.Results Before treatment,TIMI level 2 and level 3 ratio,initial corrected TIMI frame count of the observation group were significantly lower than the control group (χ2 /t =4.32,4.59,5.25,all P <0.05).After treatment,MBG level 2 or level 3 ratio,post -operative corrected TIMI frame count of the observation group were significantly higher than the control group (χ2 /t =4.11,4.85,5.87, all P <0.05).1 h after PCI treatment,the number of cases of ST fully back,the added value of EF,plague index scores of observation group were 53 cases,(8.02 ±6.94)%,(0.41 ±0.28)respectively,which were significantly higher than those of the control group 36 cases,(5.87 ±6.54)%,(0.28 ±0.27)(χ2 /t =5.32,4.32,3.65,all P <0.05).Adverse events of the two groups had no significant difference (χ2 =0.52,P >0.05).Conclusion Compared with intravenous injection,tirofiban in the treatment of acute ST segment elevation myocardial infarction by intracoronary injection can improve the level of myocardial perfusion after PCI operation,promote the recovery of left ventricular function,and has high security.

Objective To comparatively evaluate the effects of a recombinant Mtb protein ESAT 6-CFP10 ( rESAT6-CFP10 ) and a purified protein derivative ( PPD ) as skin test reagents in guinea pigs . Methods Guinea pigs were sensitized with different Mycobacteria species .After sensitization , all guinea pigs were intradermally injected with rESAT6-CFP10 and PPD.At 48 h after the injection, the size of ery-thema at injection sites was measured by using a double-blind method .For guinea pigs sensitized with viable Mtb, the size of erythema at injection sites were measured at 24 h after the injection .The positive conversion rates of skin test with rESAT 6-CFP10 and PPD were calculated .Results The results of PPD skin test were positive in all guinea pigs sensitized with viable Mtb , killed Mtb and BCG with erythema diameters of (11.4 ±0.9) mm, (11.8±1.1) mm and (13.2±0.8) mm, respectively.Positive skin test with rESAT6-CFP10 was only observed in guinea pigs infected by viable Mtb-showing erythema diameters of (13.7±5.7) mm. The skin test with rESAT6-CFP10 was negative in guinea pigs sensitized by killed Mtb-and vaccinated by BCG.The skin tests by using rESAT6-CFP10 and PPD were performed on randomly selected guinea pigs at ninth day after infection by Mycobacterium tuberculosis H37Rv.At the 2nd week, totally 24 selected guinea pigs showed positive skin test results with rESAT6-CFP10 (24/24) with erythema diameters of (19.9± 3.0) mm, while only 15 out of 24 had positive PPD skin test with erythema diameters of (6.1±5.5) mm. At the 4th week, all guinea pigs showed positive PPD skin test (3/3) with erythema diameters of (12.7± 2.5) mm.Conclusion The skin test by using recombinant ESAT 6-CFP10 protein can effectively distin-guish viable Mtb infection from BCG vaccination and killed Mtb sensitization , which is a more suitable anti-gen than PPD for the early diagnosis of Mtb infection .

Objective To establish a guinea pig model of latent Mycobacterium tuberculosis infec-tion for evaluating the effects of therapeutic vaccines .Methods Guinea pigs were subcutaneously inocula-ted with 5.0×103 CFU Mtb.The skin test was performed with 0.5μg recombinant ESAT6-CFP10 protein to detect positive conversion rates at different time points .Two weeks after Mtb inoculation , guinea pigs in model group received 5 mg isoniazid treatment ( three times a week for four weeks ) by oral gavage , while those in control group received normal saline .At the sixth week after Mtb infection , guinea pigs with and without isoniazid treatment were dissected for pathology examination .The pathological scores of liver , spleen and lung, as well as bacteria loads in spleen were compared between two groups .The established guinea pig model of latent infection was then validated by testing two reference vaccines ( AEC/BC02 and AEC/BC03 ) . Results Two weeks after Mtb inoculation , all guinea pigs showed positive EC skin test with induration area of (19.9±3.0) mm.Upon four weeks of isoniazid treatment , the guinea pigs in model group showed no pathological changes with zero scores in the examined organs .No bacterium was detected in spleen of ani-mals from model group.However, the total pathological score was 38.8±16.5 and bacteria load in spleen was (5.1±0.3) Log10 CFU with the guinea pigs from control group .Natural recurrence of tuberculosis in model group was observed after drug withdrawal .The total pathological scores were 48.5±23.9 and 51.3± 23.41.The bacterial loads in spleen were (4.5±1.3) and (4.2±1.1) Log10 CFU and bacterial loads in lung were (4.1±1.2) and (3.4±1.3) Log10 CFU respectively as verified with reference vaccines of AEC /BC02 and AEC/BC03.Conclusion Isoniazid treatment inhibited the proliferation of inoculated Mtb in guinea pigs.A guinea pig model of latent Mycobacterium tuberculosis infection is successfully established with an advantage of good repeatability .Therefore, it can be used to evaluate the effects of therapeutic vaccines on latent Mycobacterium tuberculosis infection.

Objective To establish a suitable guinea pig model for evaluating the protective effects of new TB vaccines in BCG prime-boost regimen .Methods Two different immunization strategies by using the recombinant TB vaccine were employed to boost BCG primed guinea pigs in this study .One was for short-term evaluation with 14 weeks interval between prime and boost immunization and another was for long -term evaluation with 54 weeks interval .In the short-term evaluation group , guinea pigs were boosted twice with the recombinant TB vaccine ( AEC/BC02 ) in every two weeks , while guinea pigs in the long-term evaluation group were boosted for three times with two weeks interval between each injection .A negative con-trol group ( NS→NS) and a BCG control group ( BCG→NS) were both set up in two evaluation groups .One week after the last immunization , all guinea pigs were challenged with M.tuberculosis.Six to seven weeks after bacteria challenge , all animals were euthanized and dissected to evaluate lesion scores of liver , spleen and lung, as well as the viable bacterial load in spleen .Results In the short-term evaluation group , the le-sion scores in those boosted with vaccine (3.33±5.00) was lower than that of BCG control group (5.56± 7.27) (P>0.05) and negative control group (47.00±28.11) (P=0.0001).The difference between BCG control group and negative control group in lesion score was also significant .The animals in vaccine boosted group had lower bacterial loads (0.78±1.55 log10 ) in spleen than that in BCG control group (1.06±1.87) (P>0.05) and negative control group (5.47±0.61) (P=0.0003).In the long-term evaluation group, the lesion score in those boosted with vaccine was lower (5.0±7.6) than that in BCG control group (14.4± 13.5) (P=0.0394) and negative control group (56.9±14.1) (P<0.0001).The animals in vaccine boos-ted group (1.00±1.86 log10) had lower bacterial loads in spleen than that in BCG control group (1.46± 1.94) (P>0.05) and negative control group (5.43±0.56) (P=0.01).There was a significant difference in bacterial load between BCG control group and negative group (P=0.0089).Conclusion The results suggest that the interval time between BCG-prime and boost immunization should be properly prolonged in the guinea pig model used for evaluating the protective effects of new TB vaccines in BCG prime -boost regimen .

ObjectiveTo investigate the learning curve of total thoracoscopicy cardiac surgery.MethodsClinical data of a succession of 125 patients undering total thoracoscopicy ASD and VSD repair between October 2004 to January 2010 were collected and reviewed.The procedure was perfomed by the same surgeon.The patients were divided equally into 5 groups (groupA,B,C,D and E,n =25 in each group ) according to the sequence of the operation.The operative time,extracorporeal circulation time,aortic cross-clamped time,the rate of conversion rate to thoracotomy and postoperative complications were compared between the 5 groups.ResultsThere were no statistically significant differences between the 5 groups with respect to age,gender,weight,dieases and surgical approach(P ＞ 0.05).The operative time,extracorporeal circulation time and aortic clump time in group A and group B significant longer then that in group C,group D and group E(P ＜0.05).Group A and group B was no statistically significant difference each other( P ＞ 0.05 ).Group C,D and E have no statistically significant differences between(P ＞0.05 ).The rate of conversion rate to thoracotomy and postoperative complications in 5 groups have no statistically significant differences comparative( P ＞ 0.05 ).ConclusionThe learning curve of total thoracoscopicy surgery is approximalely 50 cases.

Objective To establish guinea pig model of type Ⅰ anaphylaxis, isolate the anaphy-lactic antibody(IgE and IgG) preliminarily from sera of sensitized guinea pigs, and investigate its functional characteristics. Methods Animal model was established by sensitizing guinea pigs with OVA and Al(OH)_3, level of antibody was determined by ELISA, IgE and IgG in sera were preliminarily isolated through saturated ammonium sulphate precipitate and affinity chromatograph of Protein A. A continuous passive cutaneous ana-phylaxis test (PCA) was performed by sensitizing guinea pigs individually with IgE and IgG and then challenging at different time , and the variation of blue spots in skin were observed after challenge . Results Concentration of IgE in model group and control group were 719.3750 ng/ml and 2.5250 ng/ml, the optical density of IgG in model group and control group were 0.9921 and 0.0174, the level of two antibodies in model group were significantly higher than that of control group (P<0.05). In 9 d continuous PCA test, the blue spot induced by IgE in skin lasted for 9 days and appeared the largest when challenged at day 5. The diameter of blue spot induced by IgG was the largest when challenged at day 2 and then decreased fast. Con-clusion Anaphylactic antibodies were successfully preliminarily isolated from sera of sensitizing guinea pig, both IgE and IgG play roles in type Ⅰ anaphylaxis of guinea pig, the hypersensitive reaction induced by IgG is fast and short than that induced by IgE, and IgG may become an important surrogate marker in immunotoxic-ity evaluation(type Ⅰ anaphylaxis)of vaccine.

ObjectiveTo study the effect the low level laser irradiation in nostril combined with the electric stimulation of cerebellum on acute cerebral infarction.Methods88 patients with acute cerebral infarction were randomly divided into two groups, 45 cases in the study group who were accepted level laser irradiation in nostril combined with the electric stimulation of cerebellum and the normal medicine therapy, 43 cases in the control group who were accepted the normal medicine therapy only. The effects of two groups were observed.ResultsThe scores of the nervous function defect degree and the cerebrovascular dynamics indexes of study group were obviously increased (P<0.05 or P<0.01) compared with those before treatment. The indexes of blood viscosity were significantly decreased compared with those before treatment(P<0.01).However, all these indexes of the control group showed no significantly difference before and after treatment. ConclusionThe low level laser irradiation in nostril combined with the electric stimulation of cerebellum therapy is effective on acute cerebral infarction.It is helpful for early comprehensive recovery of motor function of the hemiplegic limbs.

ObjectiveTo investigate the clinical characteristics of patients,risk factors and preventive measures of nosocomial infection in diabetic cerebral infarction(DCI).MethodsThe clinical data of 124 DCI cases with nosocomial infection and 116 DCI cases without nosocomial infection were analyzed retrospectively.ResultsThe clinical characteristics of nosocomial infection in DCI patients were that large cerebral infarction and severity neurological deficits were very common.The patients always had long hospitalization days and poor prognosis.Invasive operation,antibiotic prophylaxis,severity neurological deficits,fasting plasma glucose,urinary albumin,size of cerebral infarction,albumin/globulin and hospitalization days were the risk factors for nosocomial infection in DCI.Among the patients,nosocomial lower respiratory tract infection was the highest(41.5%),the second one was urinary tract infection(28.1%).The case that both sites of infected was common(8.9%).Klebsiella pneumoniae(16.7%),Pseudomonas aeruginosa(15.9%),Candida albicans(12.1%) and Escherichia coli(12.1%) were the most frequent pathogens.ConclusionThe patient's condition of nosocomial infection in DCI is serious and has poor prognosis.Taking preventive measures according to the risk factors can reduce the infection rate.