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 investigate the prevalence of subclinical hypothyroidism and its relation to serum total cholesterol (TC),triglyceride (TG) levels and non-alcoholic fatty liver.Methods Serum levels of TC,TG, TSH,TT_3 and TT_4 were determined in 1 602 subjects which were divided into groups by sex and age (20-39,40- 59 and≥60 years).Fatty liver was diagnosed by type B ultrasonography.Restults ( 1 ) Prevalence of subclinical hypothyroidism was 6.6% in this population.(2) The mean levels of serum TC and TG in subclinical hypothyroidism group and normal group showed no significant difference ( both P＞0.05 ).(3) On the whole,the prevalences of subclinical hypothyroidism in hypercholesterolemia group and normal cholesterolemia group showed significant difference (P＜0.01 ).(4) In the three age groups of male and few.ale examinees,the prevalences of subclinical hypothyroidism in hypercholesterulemla group and normal cholesterolemia group showed no significant difference ( all P＞0.05 ).In the multiple regression analysis,TSH level was not related with raised TC level.(5) In the three age groups of male,there was no significant difference between the prevalences of subclinical hypothyroidism in hypertriglyceridemla group and normal triglyceridemia group ( all P＞0.05 ).In female,expect for the elderly group (＞60 years old ),the prevalence of subclinical hypothyroidism was higher in hypertriglyceridemia group than that in normal triglyceridemia.However,in the multiple regression analysis, increased TSH level was positively associated with increased serum TG level ( OR = 1.072,P=0.013 and OR = 1.102,P = 0.03 ).(6) The prevalence of subclinical hypothyroidism in non-alcobolic fatty liver group and normal group showed no significant difference ( P＞0.05 ).In the multiple regression analysis,TSH level was not the independent risk factor of non-alcoholic fatty liver (P＞0.05 ).Conclusion Subclinical hypothyroidism is not asseciated with serum TC level but positively associated with serum TG level.Subclinical hypothyroidism does not apparently increase the prevalence of non-alcoholic fatty liver.

Actins ; metabolism ; Female ; Fibroma ; metabolism ; pathology ; surgery ; Foot Diseases ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Inclusion Bodies ; metabolism ; pathology ; Infant ; Toes

B-Lymphocytes ; pathology ; Humans ; Lymphoma, B-Cell ; pathology ; Lymphoma, Large B-Cell, Diffuse ; pathology ; Male ; Middle Aged

Objective To observe whether appropriate intermittent exercise at the ischemic threshold can safely promote collateral circulation in an ischemic area of the myocardium through the increased expression of vascular endothelial growth factor(VEGF)and its receptor fetal liver kinase-1(Fik-1). Methods A balloon constrictor was surgically implanted in the first obtuse marginal coronary artery(OM1)of miniature pigs.The subjects were divided into 3 groups:a sham-operation group,a pure ischemia group,and an exercise training group.Subjects in the exercise training group performed individualized treadmill programs 30 min daily,5 d per week,for 8 weeks,including 2 two-minute episodes of exercise-induced ischemia.Two pre-exercise episodes of pure ischemia induced by brief OM1 occlusion were also conducted.Only pure ischemia was induced in the pure ischemia group,and the sham-operation group remained sedentary for the experimental period.Relative myocardial blood flow(RMBF)was measured using microspheres.VEGF and Flk-1 expression levels were measured by Western blotting and real time RT-PCR analyses.Cardiac troponin I(ctnI)levels were determined using an enzyme-linked immunosorbent assay(ELISA). Light and electron microscopy were employed to examine myocardia damage in the ischemic area.Results RMBFs in the exercise training group were significantly higher than those in the pure ischemia and sham-operation groups. RMBFs in the pure ischemia group were significantly higher than those in the sham-operation group.The expression of VEGF and Flk-1 proteins and mRNAs in the exercise training group were significantly higher than those in the pure ischemia and sham-operation groups,and the levels in the pure ischemia group were also significantly higher than those in the sham-operation group.After training,no myocardial damage and no ctnI increase was observed in the pure ischemia group.Microscopy revealed no obvious structural changes. Conclusion Intermittent exercise at the isehemia threshold intension can safely promote coronary collateral formation through upregulation of VEGF and Flk-1 expression in the ischemic myocardial area of a porcine model.

Actins ; metabolism ; Adrenal Cortex Neoplasms ; metabolism ; pathology ; surgery ; Adrenocortical Adenoma ; metabolism ; pathology ; surgery ; Antigens, CD34 ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; surgery ; Follow-Up Studies ; Hemangioma ; metabolism ; pathology ; surgery ; Humans ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Neoplasms, Multiple Primary ; metabolism ; pathology ; surgery ; Nephrectomy ; Pelvic Neoplasms ; metabolism ; pathology ; surgery

Aged ; Colorectal Neoplasms ; physiopathology ; Humans ; Intestinal Neoplasms ; complications ; Stomach Neoplasms ; complications

12E7 Antigen ; Actins ; metabolism ; Antigens, CD ; metabolism ; Cell Adhesion Molecules ; metabolism ; Female ; Granular Cell Tumor ; complications ; metabolism ; pathology ; surgery ; Humans ; Hysterectomy ; Immunohistochemistry ; Leiomyomatosis ; complications ; metabolism ; pathology ; surgery ; Middle Aged ; Ovarian Neoplasms ; complications ; metabolism ; pathology ; surgery ; Ovariectomy ; Receptors, Estrogen ; metabolism ; Uterine Neoplasms ; complications ; metabolism ; pathology ; surgery ; Vascular Neoplasms ; complications ; metabolism ; pathology ; surgery

Objective To evaluate the functional and oncological outcomes of patients with locally advanced prostate cancer (PCa) treated by hormone therapy combined with extra-fascia1 laparoscopic radical prostatectomy (LRP) plus extended lymph node dissection (ePLND).Methods From January 2004 to June 2016,a total of 255 PCa cases (pT3-4NxM0) who received LRP plus ePLND were enrolled into our study.The mean age of the patients was 67 (range 44-88) years,and median PSA level was 21.2 (range 0.6-454.0) ng/ml.The patients were divided into earlier group (from January 2004 to December 2011,160 cases) and later group (from January 2012 to June 2016,95 cases) according to different treatment periods.The baseline demographics between the two groups were similar.All patients routinely received adjuvant hormone therapy (AHT) postoperatively.The patients in the later group underwent collapsin response mediator protein 4 (CRMP4) methylation study on the prostatic biopsy preoperatively.Those with a CRMP4 methylation level ＞ 15％ or rectum/bladder neck invasion,were treated by neoadjuvant hormone therapy (NHT) for 3-6 months.Positive surgical margin (PSM),progression-free survival (PFS),cancer-specific survival (CSS),overall survival (OS) and postoperative continence rates between the two groups were analyzed and compared.Results The mean operative time of the earlier and later group were (239 ±65) min and (203±51) min,mean blood loss were (109-±65) ml and (96-±44) ml,mean dissected nodes were (19 ± 5) and (21 ± 7),respectively (all P ＞ 0.05).The total PSM rate was 19.2％,and PSM rates of the two groups were 23.1％ and 12.6％ (P =0.04).All the 255 cases received AHT and 25 cases in the later group underwent NHT.The median follow-up time was 73 months (range 10-152 months).The total 5-year PFS,CSS and OS rates were 77.7％,94.3％ and 87.1％,respectively,and the rates between groups were 73.8％ vs.86.1％ (P=0.03),93.1％ vs.98.6％ (P=0.07),and 85.0％ vs.92.8％ (P =0.11),respectively.The 1-year postoperative continence rates were 91.9％ vs.97.9％ (P =0.09).Conclusions Hormone therapy combined with LRP plus ePLND represents an oncological and functional effective option in patients with locally advanced PCa,and improved PFS might be acquired by preoperative tumor staging.

Heterokaryon incompatibility is a widespread phenomenon among fungi,controlled by specific loci termed het (for heterokaryon incompatibility).This review focuses on recent developments in our understanding of the molecular mechanisms of nonself recognition and the relationship between the death progresses of heterokaryon incompatibility and associated proteins in fungi.The deep research of heterokaryon incompatibility mechanism will hopefully reveal underlying principles of the evolution of nonself recognition systems and will find some effective method for settling the instability of protoplast fusant of fungi.