1.Effects of active immunization with Na/Ca exchanger ?1 repetitive peptides on cardiac structure and function in rats
Xiaojie BAI ; Qilong FENG ; Hui LIU ; Bowei WU
Chinese Journal of Immunology 1986;0(04):-
Objective:To observe the effects of active immunization with a synthesized repetitive peptides in the extracellular loops of Na/Ca exchanger(NCX)?1 on cardiac structure and function in rats.Methods:A repetitive peptide of 124 HNFTAGDLGPSTIVGSAAFNMF145 was synthesized,which was in line with the extracellular loops of Na/Ca exchanger(NCX)?1.Healthly male Wistar rats of 2 month age were immunized actively with the synthesized peptide as antigen repeated for 12 weeks.The control group was given Freund's adjuvant only.Specific antibodies were detected by ELISA.The cardiac function was observed by Langendorff isolated heart-perfusing assay and the hearts were prepared for routine histological evaluation.Results:All rats immunized with the peptide developed highly positive autoimmunities,indicated by the antibody titers.After 12 weeks of peptide inoculation,the cardiac functioning indexes including LVSP-LVDP,+dp/dtmax and -dp/dtmax increased much more significantly in immunized group than in control.Histological evaluation showed that the myofilaments of the control group arranged regularly and densely with better continuity,whereas the myofilaments of the immunized group were lined with disorder.Some of those were ruptured.The interstitial lymphocyte infiltration was observed.Conclusion:The results indicate that long term immunization with the synthesized repeatitive peptide in line with the extracellular parts of Na/Ca exchanger(NCX)?1 can enhance both systolic and diastolic function of rat heart,but it can also induce injury in the heart structure.This may relate with an increase of myocardial oxygen consumption owing to a long time and continued excitement of membrane ion transporters as well as their active effect in heart contraction to a larger extent.
2.Cardiac arrhythmia suppression by I K1 channel agonist in isoproterenol-induced myocardial hypertrophic rats and investigation on its mechanism
Yichun CHEN ; Chaohong LI ; Mingzhu YANG ; Xiaolu WANG ; Qilong FENG
Chinese Pharmacological Bulletin 2016;32(8):1127-1132,1133
Aim To investigate the effect of zacopride ( Zac) on cardiac arrhythmia in isoproterenol ( ISO)-in-duced myocardial hypertrophic rats and the underlying electrophysiological mechanisms .Methods ① Fifty-one rats were randomly divided into control group ( n=17 ) , ISO group ( n=17 ) and ISO +Zac group ( n =17 ) .Rat model with cardiac arrhythmia and hypertro-phy was established by intraperitoneal ISO ( 5 mg?kg -1 ) injection.②ECGs were recorded to observe the effects of Zac on arrhythmia in model rats .③ Whole-cell patch clamp was applied to record inwardly rectifi-er potassium current(IK1), resting membrane potential ( RMP ) and amplicated delayed afterdepolarizations (DADs).Results ① Echocardiographic examination showed that , left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic dimension (LVESD) significantly decreased in rats in ISO group compared with control group , whereas left ventricular posterior wall end-diastolic thickness ( LVPWd) and in-terventricular septum end-diastolic thickness ( IVSd ) increased ( P<0.05 ) , suggesting rat model of isoprot-erenol-induced myocardial hypertrophy was successfully established .② ECGs showed that 88.89% of rats in ISO group had ventricular premature beats ( VPBs ) , which significantly decreased to 11.11% after the ap-plication of Zac ( P <0.05 ) .③ Values of RMP de-creased from ( -71.05 ±1.27 ) mV in control group to (-69.38 ±1.21 ) mV in ISO group ( P<0.05 ) . After Zac administration , RMP significantly increased to ( -73.86 ±1.33 ) mV compared with control and ISO group(P<0.05).④DADs and TA incidence sig-nificantly decreased from 88.24% in ISO group to 11.76%in ISO+Zac group ( P<0.05 ) .⑤ Compared with control group , IK1 density was markedly reduced in ISO group, whereas Zac could effectively rescue IK1 suppression to normal level .Conclusions Zac, as a selective IK1 channel agonist , can significantly inhibit cardiac arrhythmia in isoproterenol-induced myocardial hypertrophic rats , which is mainly attributed to in-creased RMP by enhancing IK1 and subsequent suppres-sion of DADs.
3.Inhibitory effect of agonist of I K1 channel on arrhythmia induced by isoproterenol in rats
Chaohong LI ; Yichun CHEN ; Xuwen ZHAI ; Qilong FENG
Chinese Pharmacological Bulletin 2015;(8):1081-1084,1085
Aim To investigate the inhibitory effects of zacopride(Zac) on arrhythmia induced by isoproterenol ( ISO) and the underlying mechanisms in rats. Meth-ods ①ECGs were recorded in anesthetized rats in vi-vo to observe the effects of zacopride on arrhythmia in-duced by ISO. ② Intracellular microelectrode tech-nique was used to investigate the effects of zacopride on resting membrane potential, delayed afterdepolariza-tions ( DADs) and triggered activity ( TA) induced by ISO combined with 3. 6 mmol·L-1 CaCl2 in right ven-tricular papillary muscle of rats. Results ① In ISO group rats, ventricular premature beats ( VPB ) oc-curred frequently with ST-segment depression. Com-pared with ISO group, the incidence of VPB in ISO+Zac group decreased from 100% to 50% ( n=6 , P<0. 05 ) and the total number of VPB recorded in 1 hour significantly reduced from 1 574 ± 521 to 33 ± 40 ( n=6,P<0. 05). ② Zacopride at 1 μmol·L-1 could hy-perpolarize the resting membrane potential of right ven-tricular papillary muscle in normal rat from ( -74. 42 ± 1. 95 ) mV to ( -78. 50 ± 2. 07 ) mV ( n =6 , P <0. 05). ③ Zacopride at 1 μmol·L-1 significantly de-pressed the DADs and TA induced by ISO combined with 3. 6 mmol·L-1 CaCl2 in right ventricular papilla-ry muscle. The incidence of DADs decreased from 93. 75% in rats in ISO group to 25% in ISO +Zac group ( n =16 , P <0. 05 ) , and this antiarrhythmic effect could be reversed by 1 μmol·L-1 BaCl2 . Conclusions Zacopride, a selective IK1 channel ago-nist , can significantly inhibit cardiac arrthymia induced by ISO in rats, the mechanism of which is mainly at-tributed to zacopride-induced hyperpolarization of the resting membrane potential and subsequent suppression of DADs and TA via enhancing IK1 . These results pro-vide further evidence that to enhance IK1 moderately may be a feasible pathway for antiarrthymic therapy.
4.Inhibitory effect of zacopride on ouabain-induced arrhythmias in adult rats
Xiaolu WANG ; Mingzhu YANG ; Xiaoyan XUE ; Yuqi ZHANG ; Yichun CHEN ; Qilong FENG ; Bowei WU
Chinese Journal of Pathophysiology 2017;33(8):1371-1378
AIM: To investigate the effect of zacopride, an inward rectifier potassium channel agonist, on ouabain-induced arrhythmias in adult rats, and to explore the underlying electrophysiological mechanism.METHODS: Using ouabain to establish in vitro and in vivo arrhythmic rat models, the effects of zacopride on ouabain-induced arrhythmias were observed.The technique of whole-cell patch clamp was used to observe the effects of zacopride on inward rectifier potassium current (IK1), resting membrane potential (RMP) and delayed afterdepolarizations (DADs) in single rat ventricular myocyte.RESULTS: Zacopride at 1 μmol/L significantly reduced total number of premature ventricular beats, and the duration and incidence of ventricular tachycardia and ventricular fibrillation induced by ouabain in rat hearts in vitro (P<0.05).In anesthetized rats, zacopride at 15 μg/kg significantly reduced total number of premature ventricular beats, and the duration and incidence of ventricular tachycardia and ventricular fibrillation induced by ouabain (P<0.05).IK1 was significantly inhibited by ouabain (P<0.05), which was partially and even completely reversed by zacopride at 0.1~10 μmol/L.RMP value was significantly reduced by ouabain (P<0.05), and then increased to different levels after treatment with zacopride (0.1~10 μmol/L).Zacopride at 1 μmol/L showed its maximal effect and RMP was restored to normal level.Moreover, zacopride at 1 μmol/L markedly suppressed ouabain-induced DADs in single rat ventricular myocyte.The incidence of DADs decreased from 91.67% to 12.50% after zacopride was applied (P<0.05), and this effect was abolished by 1 μmol/L BaCl2.CONCLUSION: Inward rectifier potassium channel agonist zacopride significantly inhibits ouabain-induced ventricular arrhythmias in adult rats.The mechanism is related to increased RMP level and inhibition of DADs by activation of IK1 channel.
5.Investigation of effects of monoclonal antibody NCX-3F10against Na+/Ca2+ exchanger on rat cardiac ionic currentsand its suppression on ischemia-reperfusion induced cardiac arrhythmias
Mingzhu YANG ; Yichun CHEN ; Xiaolu WANG ; Yuqi ZHANG ; Xiaoyan XUE ; Qilong FENG ; Bowei WU
Chinese Pharmacological Bulletin 2017;33(7):934-941
Aim To observe the effect of antibody NCX-3F10 on the main ion current of rat ventricular myocytes and its effect on arrhythmias induced by ischemia/reperfusion(I/R).Methods ① The whole-cell patch clamp technique was employed to record the Na+/Ca2+ exchange current(INa/Ca) and other major ion currents in rat ventricular myocytes.② The rat models of arrhythmia induced by ischemia/reperfusion were established by ligating the left coronary artery to in vivo and in vitro.Then the effects of antibody on the arrhythmia were observed.③ The IonOptix ion imaging system was used to observe the effect of antibody on calcium transients in single ventricular myocytes.Results ① The antibody NCX-3F10 dose-dependently inhibited INa/Ca from 5 to 40 mg·L-1.The IC50 for outward and inward currents was 11.15 and 11.69 mg·L-1, and the maximum inhibitory rates were 61% and 62%, respectively.The antibody also had an inhibitory effect on calcium current(ICa-L), and had no significant effect on inward rectifier potassium current(IK1), transient outward potassium current(Ito) and sodium current(INa).② In the isolated rat heart group I/R, 100% rats showed ventricular tachycardia, and 88.89% rats had ventricular fibrillation.After administration of antibody NCX-3F10(10 mg·L-1) 5 min before reperfusion, the incidence of ventricular tachycardia decreased to 44.43%(P<0.05), and the duration of ventricular tachycardia and ventricular fibrillation was also shortened remarkably(P<0.05).③ In the anesthetized rats after administration of antibody NCX-3F10(50 μg·kg-1) 5 min before reperfusion, the incidence and duration of ventricular tachycardia,the incidence and duration of ventricular fibrillation, and total number of ventricular premature beats were significantly decreased(P<0.05).④ From 5 to 40 mg·L-1, NCX-3F10 antibody decreased calcium transient amplitude in rat single ventricular myocytes dose-dependently(P<0.05).Conclusions The NCX-3F10 antibody shows significant arrhythmic effects on ischemia-reperfusion induced arrhythmia in rats both in vitro and in vivo, the underlying mechanism of which is related to NCX and L-type calcium current inhibition and calcium overload reduction by the NCX antibody.
6.Problem-based learning method combined with the case-based learning in clinical teaching of orthopedic interns
Jun LI ; Qizhi SONG ; Hao HONG ; Qilong JIANG ; Chengbin FENG
Chinese Journal of Medical Education Research 2020;19(5):577-579
Objective:To explore the effect of the problem-based learning method (PBL) combined with the case-based learning (CBL) in clinical practice teaching of orthopedic interns.Methods:Totally 60 interns of clinical medicine who studied from July 2018 to December 2019 were randomly divided into two groups: experimental group ( n=30) receiving PBL combined with CBL teaching and control group ( n=30) receiving traditional teaching. The theory examination and satisfaction survey were conducted to assess the effects two teaching methods, and t-test was performed for data analysis using SPSS 15.0. Results:No significant difference was found in the average score of examination ( P>0.05), but the examination group showed a higher average score in the clinical case analysis than the control group ( P<0.05). The satisfaction survey showed that the students in the experimental group were more satisfied with the improvement in learning interests, self-study ability, and cooperation ability. Conclusions:PBL combined with CBL teaching method achieves good teaching effect and it is worth being recommended in clinical teaching.
7.Prevalence of infections with soil-borne intestinal nematodes amongst kindergarten children in Hangzhou
Huan YE ; Li-Hui ZHANG ; Ren ZHANG ; Jun YANG ; Hang-Lin MA ; Li-Na TONG ; Qing-Long FENG ; Qing-Hua DU ; Xiao-Jun YE ; Yingyan CAI ; Yinfang ZHU ; Qilong ZHANG ; Zhenxing YANG ;
Chinese Journal of General Practitioners 2003;0(06):-
Objective To study the prevalence of common infections with soil-borne intestinal nematodes amongst kindergarten children aged 3 to 6 years in Hangzhou,Zhejiang Province to provide evidence for determination of the priority of disease prevention and control.Methods Totally,1667 preschool children were selected from 14 kindergartens of Classes A,B and C in east,middle and west Hangzhou.Perianal skin Scotch Tape(a short strip of sealing cellophane pressure-sensitive tape)specimens were collected for detection of eggs of Enterobius vermicularis,and stool specimens for eggs of Ascaris lumbricoides,Ancylostoma duodenale and Trichuris trichiura by Kato-Katz method and saturated brine floatation,as well as questionnaire interview,for all the children.Results Two hundred and sixteen of 1667 children examined were found infected with common soil-borne intestinal nematodes,with an overall prevalence of 12.96%,4.44% for Enterobius vermicularis,8.28% for Ascaris lumbricoides,0.54% for Trichuris trichiura and 0.24% for Ancylostoma duodenale.Prevalence of infection of common intestinal nematodes was 7.31% in children of the Class A kindergartens,12.60% of Class B,and 21.47% of Class C,with statistically significant difference(?~2 = 49.95,P
8.Evaluation of optimized sequential screening program of colorectal cancer in current China.
Qilong LI ; Lingling YU ; Feng XUE ; Wanli MA ; Kaiyan YAO
Chinese Journal of Preventive Medicine 2014;48(11):995-1000
OBJECTIVETo evaluate the sensitivity and specificity of optimized sequential screening program of colorectal cancer, and provide evidence for the further optimization of colorectal cancer screening program.
METHODSUsing cluster sampling method, 4 administrative villages were selected from Jiashan county as a census district in 2011 to 2013. Volunteers of 40 to 74 years old in the census were recruited, and tested by both optimized sequential screening (including questionnaire survey and fecal occult blood test) and colonoscopy for colorectal cancer. Sensitivity and specificity of different screening methods were calculated, respectively.
RESULTSA total of 2 607 volunteers took both simultaneously screening and colonoscopy at the same time. 20 colorectal cancer cases, 85 advanced adenoma cases, 271 non-advanced adenomas cases, and 141 non-adenomatous polyps cases were detected. Sensitivity of optimized sequential screening for colorectal cancer, advanced adenomas, and non-advanced adenomas were 70.0% (14/20) , 57.6% (49/85) and 36.5% (99/271) , specificity was 68.7% (1 776/2 587) , 69.2% (1 746/2 522) and 68.9% (1 610/2 336) , respectively. Sensitivity of the fecal occult blood test of colorectal cancer, advanced adenomas and non-advanced adenomas were 70.0% (14/20) , 47.1% (40/85) and 26.6% (72/271), specificity was 79.4% (2 053/2 587), 79.9% (2 014/2 522) and 79.6% (1 860/2 336). The sensitivity of fecal occult blood test and those of optimized sequential screening for colorectal cancer, advanced adenomas was not significant (χ(2) = 0.00, 1.91, all P values > 0.05). Sensitivity of questionnaire survey of colorectal cancer, advanced adenomas and non-advanced adenomas were 10.0% (2/20), 14.1% (12/85), 12.9% (35/271), specificity was 87.6% (2 266/2 587), 87.7% (2 211/2 522), 87.6% (2 046/2 336). There were no significant difference between non-advanced adenomas. The sensitivity of advanced adenomas and non-advanced adenomas showed no significant decline when the following six term were removed from screening programs: chronic diarrhea, chronic constipation, mucus or bloody history, history of chronic appendicitis or appendectomy surgery, chronic cholecystitis or gallbladder surgery, adverse events in the history of life, while the sensitivity of colorectal cancer remained nearly the same 70.0% (14/20), 52.9% (45/85), 31.4% (85/271) (χ(2) = 0.38, 1.61, all P values > 0.05).
CONCLUSIONCurrent optimized sequential screening programs for colorectal cancer in China have a high sensitivity and specificity. However, further optimization is viable and necessary.
Adenoma ; China ; Colonic Polyps ; Colonoscopy ; Colorectal Neoplasms ; Early Detection of Cancer ; Humans ; Mass Screening ; Occult Blood ; Sensitivity and Specificity ; Surveys and Questionnaires