Objective To investigate the alteration of phosphorylated GluR1Ser831 and behavioural effects in a rat model of levodopa-induced motor complications after Ca2 +/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) inhibitor KN-93 treatment. Methods The hemi-parkinsonian rat model was produced by injecting stereotaxically 6-OHDA to right medial forebrain bundle. Then, rats were intraperitoneally treated with levodopa ( 50 mg/kg with benserazide 12.5 mg/kg,twice daily) for 22 days. On day 23 ,rats received KN-93 before levodopa administration. Rotational duration was estimated. After sacrificed, subcellualr distribution of GluR1 and phosphorylated GluR1Ser831 were observed by western blot. Results The study showed that CaMKⅡ inhibitor KN-93 prolonged rotational duration. Moreover, KN-93 could regulate subcellular distribution of GluR1 and reduce hyperphosphorylation of GluR1 Ser831, which was closely associated with levodopa-induced motor complications. The expression of membrane GluR1 and phosphorylated GluR1Ser831 was (83.4 ±4.2)% and (47.2 ±5.2)% ,respectively. Conclusions These results indicated that activation of CaMKⅡ contributed to development of motor complications, through a mechanism that involved an increase in phosphorylated GluR1 Ser831. Pharmaceuticals which act to inhibit CaMKⅡ may be useful in the treatment of the motor complications in parkinsonian patients.

Objective To study the clinical characteristics of epidemic Japanese encephalitis in 4 adult patients and to improve the level of diagnosis.Methods The clinical characteristics, laboratory results and MRI features of 4 adult patients with epidemic Japanese encephalitis hospitalized in our hospital between 2007 and 2008 was retrospectively reviewed and analyzed.Results All patients were sporadic.Two were female and others were male with the age from 34 to 68 years old and onset in summer and autumn.One patient had diarrhea at onset while others had fever and headache at onset.All patients had high fever and psychiatric symptoms.Two patients had respiratory failure.Obvious elevation of white cells in cerebrospinal fluid was seen in all patients and Japanese viral antibody of IgM was all positive whereas the image of MRI was abnormal only in one patient.Two patients had neurological sequelae.Conclusions The clinical manifestations of epidemic Japanese encephalitis in adults are severe and untypical and the respiratory failure is likely to occur.

Objective To evaluate the clinical value of bronchial artery infusion(BAI)combined with percutaneous intratumor alcohol injection(PAI)in the treatment of advanced lung cancer.Methods Thirty-two lesions confirmed by pathology,including 13 cases of primary bronchogenic carcinoma and 5 cases of pulmonary multi-metastasis tumor from hepatocellular carcinoma,were treated by 52 times of BAI and 78 times of PAI guided by fluoroscopy or CT .One cases of lung tumor was operated after the interventional therapy,and the specimen was studied with pathologic histology.Results The pathologic finding showed there was a large area necrosis in the tumor.The total effective rate of treatment was 83.8%.The 6,12 and 18 months suivival rates were 100%,77.7% and 61% respectively.Conclusion The combined interventional therapy of BAI and PAI is a more effective synthetical method for treatment only for primary tumor,but also metastasis lesions.It have better cooperative effect on the bigger lesions of lung carcinoma.

Summary: Structural nasal obstruction（SNO） is a series of diseases caused by congenital or acquired structural anatomical abnormalities of nasal airway and its surrounding tissues, which leads to increased nasal ventilation resistance. The effect of medication drugs for SNO is poor and surgical intervention is often needed. However, the abnormal structure of nasal airway is very complex, including the periphery of nasal airway, internal nasal airway, the front and rear of nasal airway and complex factors. These abnormal structures may interfere with the nasal airflow mechanics by changing the nasal ventilation volume and disrupting the symmetry of the bilateral nasal cavity, and finally lead to subjective feeling of nasal obstruction. In addition, the structure of nasal airway has plasticity. After the abnormal structure appears, the corresponding compensation of nasal airway can occur to ensure normal nasal ventilation and bilateral nasal cavity symmetry. Therefore, the SNO is the result of the failure of nasal airway remodeling after the appearance of abnormal structures. The etiology of SNO is complex, involving original structural abnormalities, nasal symmetry changing and nasal airway structure remodeling. Therefore, accurate identification of the main factors leading to SNO is the vitalpremise of making personalized nasal ventilation surgery.

OBJECTIVE To compare the effect of four 5-hydroxytryptamine type 4 (5-HT4) receptor agonists:cisapride,zacopride,macopride and 2-[1-(4-piperonyl) piperazinyl]-benzothiazole (BZTZ),on rat cardiac inward rectifier potassium channel (IK1)and heart rhythm.METHODS The whole-cell configuration of patch-clamp technique was used to record effects of 5-HT4 receptor agonists onIk1 in enzymatic dissociated rat ventricular myocytes or Kir2.1 transfected HEK 293 cells.Western blotting was used to observe the expression of Kir2.1 channel exposed 24 h to agents in ventricular myocytes.Langendorff-perfused hearts were perfused with four agents respectively for 30 min.The electrocardiogram was recorded simultaneously.RESULTS BZTZ,cisapride and mosapride 0.1-10 μmol· L-1 decreasedIk1 in a concentrationdependent manner.At the same concentration (1 μmol· L-1),BZTZ showed the most potent inhibition onIκ1 (P＜0.01),followed by cisapride.Mosapride showed slight inhibition efficiency.However,zacopride enhanced Iκ1 (P＜0.01).In Kir2.1 heterologous expression systems,zacopride activated Kir2.1 current (P＜0.01) while mosapride had no effect.In ex vivo Langendorff-perfused hearts,BZTZ and cisapride 1μmol· L-1 elicited singnificant rhythm disturbances,and the total of premature ventricular beats (PVB) were 159±28 and 61±13.50％ (4/8) (P＜0.05) and 25％ (1/8) of the hearts exhibited ventricular tachycardia (VT),while 37.5％ (3/8) and 12.5％ (1/8) of the hearts exhibited ventricular fibrillation (VF),respectively.Mosapride and zacopride had no side effects on heart rhythm.Zacopride also suppressed BZTZ-or cisapride-induced arrhythmias.BZFZ had the strongest proarryhthmic potency among the 5-HT4 agonists,followed by cisapride,mosapride and zacopride.CONCLUSION Iκ1 might be an independent risk factor for arrhythmogenesis and a new target for screening safe 5-HT4 receptor agonists and gastrointestinal prokinetic agents.

OBJECTIVE:To systematically evaluate therapeutic efficacy and safety of Yupingfeng powder in adjavant therapy of allergic rhinitis,and to provide evidence-based reference for clinical treatment. METHODS:Retrieved from Wanfang database,VIP,CJFD,CBM,Cochrane Library,EMBase and PubMed,RCTs about Yupingfeng powder combined with chemical medicine (trial group)vs. chemical medicine alone in the treatment of allergic rhinitis were collected. Meta-analysis was conducted by using Rev Man 5.2 statistical software after data extraction and quality evaluation according to Cochrane system evaluation method 5.1.0. RESULTS:A total of 15 RCTs were included,invovling 1366 patients. The results of Meta analysis showed that response rate [OR=3.95,95%CI(2.80,5.58),P<0.001],recurrence rate [OR=0.37,95%CI(0.22,0.63),P<0.001] and the incidence of ADR [OR=0.15,95%CI(0.06,0.35),P<0.001] in trial group were significantly higher than control group,with statistical significance. CONCLUSIONS:Yupingfeng powder in adjuvant therapy of allergic rhinitis show good therapeutic efficacy and can reduce recur-rence rate with good safety.

Objective To study the effects of transcranial magnetic stimulation (TMS) on learning and memory, and angiogenesis and the dendritic structure of hippocampal CA3 pyramidal neurons after cerebral infarction. Methods Forty-eight male Sprague-Dawley rats were divided into a sham operated group, a model group and a TMS group (n = 16). Rat models of focal cerebral infarction were established with unilateral middle cerebral artery (MCA) suture occlusion in the model and TMS groups. The rats of the TMS group were given 4 weeks of TMS treatment beginning 1 day after the infarction (2 times per day, 30 pulses per time). Their learning and memory abilities were tested with a Y-maze. Angiogenesis and the dendritic structure of their hippocampal CA3 pyramidal neurons were detected after 4 weeks. Results Compared with the model group, learning and memory improved significantly in the TMS group. The average microvessel density of the hippocampus in the TMS group was significantly more than in the model group. The total length of apical dendrites of hippocampal CA3 pyramidal neurons in TMS group was significantly longer than in the model group. Conclusions The improved learning and memory observed following TMS treatment are likely to be related to changes in angiogenesis, the dendritic.structure of the hippocampal CA3 pyramidal neurons, and enhanced synaptic plasticity.

The artificial 5-helix can inhibit the formation of trimer-of-hairpins structure during the course of HIV-directed membrane fusion and then inhibit human immunodeficiency virus (HIV) infecting target cells. But 5-helix was apt to form inclusion body when expressed directly in prokaryotic cell and was difficult to renature, which causes inconvenience to future study. We found a proper expression vector by simulating protein structure. We simulated its proper conformation in two vectors pGEX-6P-1 and pET44b by homology modeling. The contrast of conformations showed that the energy of salvation of its fusion protein with NusA in vector pET44b was higher than its fusion protein with glutathione-S-transferase (GST) in pGEX-6P-1 and its restriction site lay on the surface of its fusion protein in vector pET44b. 5-helix gene was amplified from pGEX-6P-1-5H by PCR, and was ligated to pET44b to construct recombinant vector pET44b-PSP-5Helix after tested correctly by enzymes digestion. The recombinant vector was transformed into Escherichia coli BL21 (DE3) to express 5-helix protein at different temperatures. Aim protein was purified with Ni column and GST column, and was determined by SDS-PAGE. Then the purified 5 -Helix was used to test the inhibitive activity of pseudo HIV virus infecting GHOST-CXCR4. Results show that its fusion protein with NusA can be effectively soluble expressed and easier to be cleaved, and that the purified 5-helix can efficiently inhibit pseudo HIV virus infecting GHOST-CXCR4 and its IC50 value is (22.77 +/- 5.64) nmol/L, which lay the foundation to further discuss the application in HIV-1 infection.
Carrier Proteins ; biosynthesis ; genetics ; Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; genetics ; HIV Envelope Protein gp41 ; metabolism ; HIV-1 ; genetics ; Peptides ; genetics ; Repetitive Sequences, Nucleic Acid ; genetics ; Viral Fusion Proteins ; genetics ; Virus Internalization ; drug effects

Aim To examine the effect of zacopride,a specific inward rectifier potassium channel(IK1)agonist,on L-thyroxine(T4)-induced ventricular remodeling and the underlying mechanism.Methods SD rats were randomly divided as control,L-thyroxine(L-thy,1 mg·kg-1·d-1,ig,10 d)model,L-thy +zacopride(5,15,50 μg·kg-1,respectively,ip),L-thy+zacopride(15 μg·kg-1)+chloroquine(7.5 μg·kg-1,ip)and L-thy+captopril(100 mg·kg-1·d-1,drinking water)groups.Echocardiography and cardiac hypertrophic indexes were measured to confirm the establishment of the ventricular remodeling model.The changes of IK1 and L-calcium current(ICa-L)were detected by whole cell patch clamp technique.The confocal microscopy and fluorescent indicator Fluo-4 were applied to examine the intracellular Ca2+ concentration([Ca2+]i)of isolated adult rat ventricular myocytes.Results L-thyroxine induced left ventricular hypertrophy with increased ratio of heart weight(HW)to body weight(HW·BW-1),ratio of left ventrical weight(LVW)to body weight(LVW·BW-1),left ventricular dimension in diastole(LVIDd),left ventricular dimension in systole(LVIDs),interventricular septum thickness(IVS)and decreased ejection fraction(EF),fractional shortening(FS)(P<0.01).Patch clamp data suggested IK1 was downregulated,while ICa-L was upregulated(P<0.01).In isolated adult cardiomyocytes,L-thyroxine increased the cell area and [Ca2+]i(P<0.01).Zacopride treatment obviously alleviated cardiac remodeling,improved cardiac function,reversed the changes of IK1 and ICa-L,and significantly attenuated intracellular calcium overload(P<0.01).The optimum dose of zacopride in vivo was 15 μg·kg-1 at which the effect was compared favourably with captopril,a classical anti-remodeling agent.Low-dose IK1 atagonist chloroquine could reverse the effect of zacopride(P<0.01).Conclusion Via activating IK1,zacopride could significantly decrease Ca2+ influx and intracellular calcium overload thereby inhibiting L-thyroxine-induced cardiac ventricular remodeling.

Objective:To describe the application of polymethylmethacrylate (PMMA) augmentation of cement-injectable cannulated pedicle screws for the treatment of degenerative lumbar scoliosis with osteoporosis.Methods: Retrospective cohort study was used to compare cement injectable cannulated pedicle screws (CICPs) group with PMMA augmentation and control group with traditional method in the correction surgery for Lenke-silva level Ⅲ and level Ⅳ degenerative scoliosis cases with osteoporosis.Both groups were followed up for 1 year.The clinical results were assessed by visual analog scale (VAS) of pain on lumbar and lower limbers,Oswestry disability index (ODI) score and EuroQol-5 dimensions (EQ-5D) score.The coronal major curve Cobb angel in coronal plane and thoracic kyphosis Cobb angle,lumbar lordosis Cobb angle and sagittal vertical axis (SVA) in sagittal plane were tested in whole long spine X ray.The fusion rates were evaluated by lumbar X ray and dynamic X ray.Results: In this study 34 cases were enrolled,15 cases in CICPs group and 19 cases in control group.The general characteristics including age,gender,weight,height,BMI and BMD were without statistical difference between the two groups.There were (5.7±2.2)PMMA augmentation screws in CICPs group.The operation time,blood loss and blood transfusion were higher in CICPs group than in control group,but without statistical difference.Lumbar VAS,lower limbers VAS,ODI score and EQ-5D were all better in 1 month post-operation,6 months postoperation and 1 year postoperation than in preoperation in both groups.lumbar VAS scores of CICPs group in 6 months postoperation(CICPs group 3.1±1.3 vs.control group 4.4±1.4,P<0.01) together with lumbar VAS scores (CICPs group 3.3±1.0 vs.control group 5.2±1.4,P<0.01),ODI scores (CICPs group 22.7±17.2 vs.control group 31.4±18.5,P<0.01) and EQ-5D in 1 year postoperation (CICPs group 2.9±2.0 vs.control group 3.5±2.5,P<0.01)were lower than those of control group.The coronal major curve Cobb angels were all lower in 1 month postoperation,6 months postoperation and 1 year postoperation than in preoperation in both groups;thoracic kyphosis Cobb angle and lumbar lordosis Cobb angle were all higher in 1 month postoperation,6 months postoperation and 1 year postoperation than in preoperation in both groups.The coronal major curve Cobb angel was lower in CICPs group than that in control group in 1 year postoperation (CICPs group 17.6°±6.9° vs.control group 21.2°±7.2°,P<0.01)and thoracic kyphosis Cobb angle was higher in CICPs group than that in control group in 6 months postoperation (CICPs group-33.5°±8.8 °vs.control group-28.9°±8.3°,P<0.01)and 1 year postoperation(CICPs group-33.0°±8.1° vs.control group-26.3°±7.4°,P<0.01) together with lumbar lordosis Cobb angle were higher in CICPs group than that in control group in 1 year postoperation(CICPs group 26.4°±8.1° vs.control group 22.1°±7.3°,P<0.01).Conclusion: Polymethylmethacrylate augmentation of bone cement-injectable cannulated pedicle screws for the treatment of degenerative lumbar scoliosis with osteoporosis was effective and safe,the short-term clinical result was good.