To study the antiarrhythmic effect of the newly developed alpha/beta-blocker TJ0711, a variety of animal models of arrhythmia were induced by CaCl2, ouabain and ischemia/reperfusion. Glass microelectrode technique was used to observe action potentials of right ventricular papillary muscle of guinea pig. The onset time of arrhythmia induced by CaCl2 was significantly prolonged by TJ0711 at 0.75, 1.5 and 3 mg x kg(-1) doses. TJ0711 (1.5 and 3 mg x kg(-1)) can significantly shorten the ventricular tachycardia (VT) and ventricular fibrillation (VF) duration, the incidence of VF and mortality were significantly reduced. On ischemia-reperfusion-induced arrhythmic model, TJ0711 (0.25, 0.5, 1 and 2 mg x kg(-1)) can significantly reduce the ventricular premature contraction (PVC), VT, VF incidence, mortality, arrhythmia score with a dose-dependent manner. At the same time, rats serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities decreased significantly by TJ0711 (1 and 2 mg x kg(-1)). Ouabain could cause arrhythmia in guinea pigs, when TJ0711 (0.375, 0.75, 1.5 and 3 mg x kg(-1)) was given, the doses of ouabain inducing a variety of arrhythmia PVC, VT, VF, cardiac arrest (CA) were significantly increased with a dose-dependent manner. In the TJ0711 0.1-30 micromol x L(-1) concentration range, guinea pig right ventricular papillary muscle action potential RP (rest potential), APA (action potential amplitude) and V(max) (maximum velocity of depolarization) were not significantly affected. APD20, APD50 and APD90 had a shortening trend but no statistical difference with the increase of TJ0711 concentration. TJ0711 has antiarrhythmic effect on the sympathetic nerve excitement and myocardial cell high calcium animal arrhythmia model. Myocardial action potential zero phase conduction velocity and resting membrane potential were not inhibited by TJ0711. APD20, APD50 and APD90 were shortened by TJ0711 at high concentration. Its antiarrhythmic action mechanism may be besides the action of blocking beta1 receptor, may also have a strong selective blocking action on alpha1 receptor and reducing intracellular calcium concentration.
Action Potentials ; drug effects ; Adrenergic alpha-Antagonists ; administration & dosage ; pharmacology ; Adrenergic beta-Antagonists ; administration & dosage ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; administration & dosage ; pharmacology ; Arrhythmias, Cardiac ; blood ; chemically induced ; etiology ; pathology ; physiopathology ; Calcium Chloride ; Creatine Kinase ; blood ; Dose-Response Relationship, Drug ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; Lactate Dehydrogenases ; blood ; Male ; Myocardial Reperfusion Injury ; complications ; Myocytes, Cardiac ; drug effects ; physiology ; Ouabain ; Papillary Muscles ; cytology ; Phenoxypropanolamines ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective To evaluate the effect of dexmedetomidine on myocardial injury induced by renal ischemia-reperfusion (I/R) injury in rats.Methods Twenty-four male Wistar rats,weighing 280-300 g,were randomly divided into 3 groups (n =8 each):sham operation group (group S),group I/R and dexmedetomidine group (group Dex).Renal ischemia was induced by occlusion of bilateral renal arteries for 45 min followed by reperfusion in I/R and Dex groups.At 20 min before ischemia,dexmedetomidine 50 μg/kg was injected intraperitoneally in group Dex,and the rest procedures were similar to those previously described in group I/R.The rats were sacrificed at 24 h of reperfusion and myocardial specimens were obtained for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity.The apoptosis in cardiomyocytes was examined by flow cytometry.Apoptosis index was calculated.The expression of Bcl-2 and Bax was detected by immunohistochemistry,and Bcl-2/Bax ratio was calculated.Results Compared with group S,apoptosis index and MDA content were significantly increased in I/R and Dex groups,Bcl-2/Bax ratio was decreased in group I/R,and Bcl-2/Bax ratio was increased in group Dex.Compared with group I/R,apoptosis index and MDA content were significantly decreased,and SOD activity and Bcl-2/Bax ratio were increased in group Dex.Conclusion Dexmedetomidine can attenuate myocardial injury induced by renal I/R in rats,and the mechanism may be related to inhibited apoptosis in cardiomyocytes and reduced lipid peroxidation.

Objective To induce the immunoincompetence of T cells to oxidized-low density lipoprotein(ox-LDL)in vitro,in order to prevent immune injuries in atherosclerosis(AS)and to find new strategies to prevent AS.Methods Monocytes were separated from peripheral blood to induce dendritic cells (DC).DCs were treated with LPS(30 ng/m1),ox-LDL(10μg/m1)and LDL(10μg/m1)for 48 h,respectively.Then DCs were mixed with allogeneic T lymphocytes to earry out mixed lymphoeytes reaction (MLR).CTLA4Ig in different concentrations was added into the MLR of ox-LDL group.MTr method was used to assay the proliferation of T cells.The CD25 expression and apoptosis of T cells in MLR were tested by flow cytometry.And the excretion of IL-2,IFN-γ and IL-4 were assayed by ELISPOT method.Results SI of the ox-LDL group was higher than that of the LDL group significantly(DC:T=1:5,1.6717±0.3152vs 1.4250±0.2874.P<0.05;DC:T=1:10,1.5458±0.2748 vs 1.3352±0.2991,P<0.05),and CTLA4Ig inhibited the SI of the ox-LDL group in dose-dependence(CTLA4Ig 1.25μg/ml,0.96±0.30 vs μg/ml 1.29±0.28 vs 1.64±0.33 P<0.05).CTLA4Ig caused the decrease of CD25 expression(CTLA4Ig 1.25 μg/ml,11.26±0.58 vs 14.25±1.02,P<0.05;CTLA4Ig 10μg/rnl 8.42±0.45,P<0.01)and induced apoptosis of T cells in MLR(CTLA4Ig 1.25μg/ml,12.54±3.69 vs 6.09 4-2.24,P<0.05;CTLA4Ig 10μg/ml,26.87±5.06 VS 6.09±2.24,P<0.01).CTLA4Ig caused the decrease of ELISPOT counts of IL-2(CTLA4Ig 1.25μg/ml,386±42 VS 534±54,P<0.05;CTLA4Ig 10μg/rnl,230±27 VS 534±54,P<0.01)and IFN-γ(CTLA4Ig 1.25μg/ml,445±48 VS 672±46,P<0.05;CTLA4Ig 10μg/ml,193±39 VS 672±46,P<0.01),while that of IL-4 increased(CTLA4Ig 1.25μg/ml,401±32 VS 332±41,P<0.05;CTLA4Ig 10μg/ml,453±57 VS 332±41,P<0.05).Conclusion CTLA4Ig can induce T cens immunoin competence to ox-LDL in vitro by inhibiting T cells activation,inducing T cells apoptosis and TH 1/TH2 immune deviation.

AIM: Recently,it is widely accepted that atherosclerosis(AS) is an auto-immune related disease and the oxidized-low density lipoprotein(ox-LDL) is the most important AS-related antigen.In order to prevent immune injuries in AS and find new strategies to prevent AS,the immune tolerance of T cells to ox-LDL in vitro was induced in this study.METHODS: Human monocytes were separated from peripheral blood to induce dendritic cells(DCs).DCs were treated with LPS(30 ?g/L),ox-LDL(10 mg/L) and LDL(10 mg/L) for 48 h.Then DCs were mixed with allogenic T lymphocytes to carry out mixed lymphocytes reaction(MLR).CTLA4Ig in different concentrations was added in the MLR of ox-LDL group.MTT method was used to assay the proliferation of T cells and expressed in stimulation index(IS).The CD25 expression and apoptosis of T cells in MLR were tested by flow cytometry.The excretion of IL-2,IFN-? and IL-4 was assayed by ELISpot method.RESULTS: SI in ox-LDL group was higher than that in LDL group significantly(P

?AIM: To discuss the effect of laser exposure on visual acuity and macula.?METHODS: Retrospective and consecutive case series. A retrospective analysis of 11 patients (11 eyes) with laser retinal injury was carried out from January 2014 to June 2015 in Ophthalmology Department of No. 474 Hospital of Chinese PLA. All individuals underwent visual acuity, best corrected visual acuity ( BCVA ) , and spectral-domain optical coherence tomography ( SD-OCT) for macular at first visit, and fundus fluorescein angiography ( FFA ) , visual field, and multifocal electroretinogram ( mf ERG ) were perform if necessary. Symptomatic therapies, supportive therapies and pars plana vitrectomy ( PPV ) were performed depended on the patient’s condition. The patients were followed-up at 1, 3 and 6mo after the first visit, and patients were undertaken visual acuity, BCVA, macular SD-OCT and so on.?RESULTS: Eight patients ( 73%) were under 18 years old and all patients were young males, who were injured by laser pointers when playing. Three patients ( 27%) over 18 years old were injured accidentally at work. Ten (91%) patients’ BCVA were ≤0. 3, while one ( 9%) patient’s BCVA was higher ≥0. 3. Full-thickness macular holes ( the diameter 224-519 μm ) were detected in 10 patients (91%), while sub-foveal RPE changes and IS/OS injury in 1 patient ( 9%) . Macular hole with traction or cystoid edema in 6 eyes (55%) were received PPV, while the other 5 eyes ( 4 eyes with stable macular hole and 1 eyes with RPE injury ) received conservative treatment. Macular hole closed successfully in 1 eye ( 17%) after PPV, while macular hole in the other 5 eyes ( 83%) were stable after PPV of which the cystoid edema faded. The 4 patients with macular hole and 1 patient with RPE injury were stable during follow-up period. However, the BCVA in all patients had no significant improvement at end.?CONCLUSION: Exposure to laser devices could lead to severe macula injury that could reduce central vision, which is permanent.

Objective To develop a specific trans-splicing intron ribozyme type Ⅰ-mediated dual reporter gene system (Rib53-Fluc-tk) for targeting CEA.Methods The novel CEA-targeting trans-splicing ribozyme with the downstream reporter system (Rib53-Fluc-tk) was constructed by genetic engineering technology.The trans-splicing reaction product was evaluated using the 131I-5-iodo-2'-fluro-l-beta-D-arabinofuranosy-luracil (FIAU) cellular uptake rates and the bioluminescence.Two-sample t test,the analysis of variance and the least significant difference (LSD) t test was performed for data analysis.Results The sequence of Rib53-Fluc-tk was proved by gene-sequencing test.Human MCF-7 breast cancer cells showed a high ratio of firefly luciferase/renilla luciferase (0.64±0.10,n =4).A 520 bp band of product existed,which matched with the predicted size using RNA from cells transfected with Rib53-Fluc-tk in MCF-7.Signals were detected by bioluminescence in human embryonic kidney 293T cells co-transfected with Rib53-Fluc-tk and pCDNA3.1-CEA.The labelling rate of 131I-FIAU was (64.02±4.79)％ (n =3).The radiochemical purity was (95.96± 1.07)％ (n=3),and the stability of the radiocompound remained high in human serum at least for 24 h.The uptake of 131I-FIAU in 293T cells transfected with Rib53-Fluc-tk was (0.31±0.01)％ (n=4),while it increased with the incubation time in 293T cells co-transfected with pCDNA3.1-CEA and Rib53-Fluc-tk and reached (1.40±0.06)％ at 4.5 h (F=1 007.29,t=136.34,both P＜0.01).Conelusions A novel and specific reporter gene in the cellular level was established.Taking advantage of trans-splicing reaction of the ribozyme,it could improve the specificity of the reporter gene imaging.

Objective:To analyse the methord and effects of intermaxillary traction(IMT)screws used in the treatment of jaw frac-ture.Methods:In the treatment of 1 68 cases of jaw fracture IMT screws were used for the restoration of normal and stable occlusion. The screw number,position,traction effect and postoperative complications of the treatment were analysed.Results:705 screws were used in 168 patients,4 screws were used in each of 147 cased (88%),6 in 12(7%),5 in 9(5%).336(47.7%)screws were fixed between the roots of first and second premolar,292(41 .4%)between the roots of canine and first premolar,50 (7.1%)be-tween the roots of second premolar and first molar,27(3.8%)between the other tooth roots.Normal postoperative occlusion relation was achived by the use of screws in 92 cases without traction.Occlusion disharmony or deviation was found in 76 cases by the used of screws and was restored to normlal by 1 4-day traction in 71 cases.The total efficiency of the treatment was 97%.Pain of the mucosa surrounding the screws was observed in 23 cases (1 3.7%).Root damage,traction screw loosening and adjacent tooth dislocation were observed in 1 3(1 .8%),1 1 (1 .6%)and 2(0.3%)cases respectively.Conclusion:For the fixation of IMT screws,the posi-tions between tooth root from canine to first molar were most common and safe.The fixation point should be in 5 ~8mm below the gin-gival margin.Use of 4-6 screws can meet treatment need.

Objective:To observe the artifacts produced by dental metal crown made from different materials on magnetic resonance imaging (MRI).Methods:Mental crows made from Co-Gr,Ni-Gr,low-Ti alloy and Pure-Ti were respectively fabricated for upper right second premolar of a ripe crossbreed dog.The 4 different casting crowns were respectively put on experimental tooth and head MRI scan was carried out with 4 sequences of 1.5 T and 6 sequences of 3.0 T MRI respectively.The existence and extent of the arti-facts were assessed and compared.Results:On both 1.5 T and 3.0 T MRI,the Go-Gr alloy crown exhibited significantly wider arti-facts than the others (ANAVO analysis,P<0.01).There were no significant differences among Ni-Gr,low-Ti alloy and Pure-Ti on 1.5 T MRI(P>0.05).On 3.0 T MRI the artifacts produced by Ni-Gr was larger than that by low-Ti alloy or Pure-Ti(P<0.05,be-tween low-Ti alloy and pure-Ti,P>0.05).By any of the test sequence either on 1.5 T or on 3.0 T,the Co-Gr alloy produced arti-facts in the most slices of MRI imaging and Pure-Ti in the least.Conclusion:Go-Gr alloy may produce larger artifacts than Ni-Gr, low-Ti alloy and Pure-Ti on MRI.

Objective:To elucidate the changes in apparent diffusion coefficients(ADC)by quantify diffusion weighted (DW)magnetic resonance imaging(MRI)in patients with Alzbeimer's disease(AD),and the relationship between micro-structure changes of white matter(WM)and the cognitive impairment thereof.Methods:The DW-MRI was performed in 30 probable AD patients and 30 normal controls with normal-appearing white matter(NAWM).The ADC was measured in different WM areas.The neurologic and neuropsychological assessments were examined with mini-mental state examination(MMSE)in patients.The ADC were determined in standard regions of the frontal,temporal,occipital and parietal white matter,genu,splenium of the corpus callosum.Results:The value of ADC was higher in frontal,splenium corpus callosum,temporal,and parietal white matter of AD group than that of control(P ＜ 0.01).There was no significant difference in the ADC value of genu and occipital white matter between AD and control groups(P＞ 0.05).The score of MMSE was 24.1±0.8 in AD group.The ADC values of parietal,splenium of the corpus callosum and frontal white matter were significantly negatively correlated with MMSE scores in AD group(P ＜ 0.05 or P ＜ 0.01).There was no correlation between the ADC values of genu of the corpus eallosum,temporal and occipital white matter with the MMSE score(P ＞ 0.05).Conclusion:The quantitative DWI analysis of MRI DWI may be helpful in assessing WM abnormalities in AD.The parietal WM abnormalities may play an important role in the development of dementia.It was showed that Alzheimer's cognitive decline with ADC value and micro-structure of white matter was closely related.

Objective In order to get reference data for diagnosis of clinical genetic disease through analyzing chromosome ab‐normality types and rates in 885 patients who ask for cytogenetics consultation in recent years .Methods 324 newborns who asked for cytogenetics consultation because of high risk factors in down′s screening during pregnancy or found abnormality in physical ex‐amination after birth and 561 patients with history of spontaneous abortion ,infertility or fetal death ,growth or mental retardation , sexual abnormality were examined for karyotype analysis .Results 116 cases of chromosome abnormal karyotypes were detected , count for 13 .11% ,among which ,40 cases(34 .48% ) are chromosomal aberration .Chromosome abnormality types and rates are dif‐ferent in patients with different type of diseases .Conclusion Abnormalities in chromosome numbers and sex chromosome abnor‐mality account for the main causes of growth and mental retardation ,abnormalities of sexual differentiation and development ;but for couples suffered from spontaneous abortion ,polymorphism and structure abnormalities takes up the highest portion .