1.Design and expression of FGF23 inhibitor in Pichia pastoris
Xiu-mei ZHANG ; Jia-jun CUI ; Yin-jie JIANG ; Nan-yan FU ; Jing YANG ; Zhi-xing ZHOU ; Ning-yuan ZHANG ; Kai QIAN
Acta Pharmaceutica Sinica 2019;54(2):380-385
Hypophosphatemia is a common metabolism disease in humans. Fibroblast growth factor 23 (FGF23) inhibits phosphate reabsorption by targeting on the renal tubules. FGF23C-tail contains 73 amino acids from C-terminus of FGF23, serves as an inhibitor of FGF23, and can increase phosphate reabsorption. Therefore, FGF23C-tail is an important drug for hypophosphatemia. In this paper, we constructed a fusion protein of FGF23C-tail with HSA, and investigated the expression of the fusion protein in the
2. Regulation Mechanisms of Sirt7 in Pathophysiological Activities
Yang-Yang LU ; Yan LI ; Cheng LUO
Chinese Journal of Biochemistry and Molecular Biology 2022;38(5):570-576
Silent mating type information regulator 2-related enzymes or sirtuin family proteins are nicotinamide adenine dinucleotide (NAD
3.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.
4.Efficacy of combination therapy of lamivudine and adefovir dipivoxyl for patients with hepatitis B-induced decompensated liver cirrhosis.
Jing YANG ; Xuan ZHU ; He WANG
Journal of Central South University(Medical Sciences) 2012;37(12):1269-1273
OBJECTIVE:
To evaluate the efficacy of combination therapy of lamivudine (LAM) and adefovir dipivoxyl (ADV) for patients with hepatitis B-induced decompensated cirrhosis.
METHODS:
A total of 81 patients were randomly divided into a combination group and an ADV group over 48 week treatment course. The combination group were treated with LAM (100 mg/d) plus ADV (10 mg/d), and the ADV group with ADV (10 mg/d ) for 48 weeks. All patients received hepatic function support and symptomatic treatment. The levels of HBV DNA, liver function, Child-Pugh scores and HBV DNA indicators were observed before and after the treatment.
RESULTS:
At week 4, the mean reduction of HBV DNA was 1.83 lgIU/mL, 17.9% of the patients achieved undetectable HBV DNA and 28.2% showed normal ALT in the combination group. The counterpart in the ADV group was 0.96 lgIU/mL, 5.3% and 10.5%. At week 4, 12, 24 and 48, the differences in the mean reduction of HBV DNA, undetectable HBV DNA and ALT normalization were statistically significant between the 2 groups. The difference in HBeAg negative conversion rates and HBeAg seroconversion at week 24 and 48 was not significant.
CONCLUSION
The combination therapy results in HBV suppression and improved liver function and Child-Pugh score. The combination treatment has an advantage over ADV due to low drug resistance rate and good tolerance.
Adenine
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administration & dosage
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analogs & derivatives
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Adult
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Antiviral Agents
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therapeutic use
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Drug Therapy, Combination
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End Stage Liver Disease
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drug therapy
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etiology
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Female
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Hepatitis B, Chronic
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complications
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Humans
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Lamivudine
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administration & dosage
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Liver Cirrhosis
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drug therapy
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etiology
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physiopathology
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Male
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Middle Aged
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Organophosphonates
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administration & dosage
5.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.
6.Clinical outcomes of different transferring methods in patients who received different numbers of oocytes
Yanli LIU ; Zhen LI ; Wenying WANG ; Yichun GUAN ; Chunyan SHEN ; Yue YANG ; Xingling WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2015;(6):824-828
Objective To compare the clinical outcomes of two D3 embryo and single blastocyst transfer in patients retrieving different oocytes, so as to provide data support for selecting a clinical transfer strategy. Methods We made a retrospective analysis of patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI)between January and December 2014 in the Reproductive Medicine Center,the Third Affiliated Hospital of Zhengzhou University.The patients were divided into three groups according to the number of oocytes received:Group A (5-9 oocytes),Group B (10 - 14 oocytes)and Group C (≥ 1 5 oocytes).Patients in each group all received four different transfer methods as follows:transfer of two fresh D3 embryos (a ),transfer of one fresh blastocyst (b ),transfer of two D3 frozen embryos (c ),and transfer of one frozen blastocyst (d ).We compared the 2PN fertilization rate of oocytes,rate of available embryos and rate of good embryos among the three groups.We also compared the embryo implantation rate,biochemical pregnancy rate,clinical pregnancy rate, multiplets rate and abortion rate among the four transfer methods in each group.Results ① There were 667, 573,and 479 transfer cycles in Group A,Group B and Group C,respectively.The 2PN fertilization rate of IVF and available embryos rate was significantly higher in Group A than in Group B and Group C (P =0.003/P <0.001).② There was no significant difference in biochemical pregnancy rate,clinical pregnancy rate or abortion rate with the four transfer methods in Group A (P >0.05),but the implantation rate of c was significantly lower than that of a and d (P =0.027/0.020),d had a higher implantation rate than a and c in Group B (P =0.005/0.001).In Group C,the biochemical pregnancy rate and clinical pregnancy rate of d were significantly higher than those of a (P =0.048/0.027)and c (P =0.003/0.001).Patients in Group C also had a higher implantation rate than D3 embryos (P <0.05).③ The multiple pregnancy rate of single blastocyst transfer decreased compared with D3 embryos transfer in the three groups (P <0.05).Conclusion Single blastocyst transfer has both higher implantation rate and lower multiple pregnancy rate in high response patients (1 5 or more oocytes received).For patients who received 5-9 and 10-14 oocytes,D3 embryos have a similar clinical pregnancy rate with that of single blastocyst but a higher multiple pregnancy rate.Single vitrified-warmed blastocyst transfer has a higher clinical pregnancy rate.It is the best transfer method for patients who received more than 10 oocytes.
7.Influence of high body mass index on IVF-ET pregnancy outcome in patients with polycystic ovary syndrome *
Hua LOU ; Xingling WANG ; Lijun SUN ; Yichun GUAN ; Yang GOU ; Xuemei WANG ; Weiwei LI
Chongqing Medicine 2013;(27):3246-3248
Objective To investigate the influence of high body mass index (BMI) on in vitro fertilization and embryo transfer (IVF-ET) pregnancy outcome in the patients with polycystic ovary syndrome (PCOS) .Methods A retrospective cohort study was conducted using existing data on 224 PCOS patients with IVF-ET by the standard long protocol in this hospital from Jan 2009 to Dec 2011 .All patients were divided into 2 groups according to BMI ,the high BMI group(BMI≥24 .0 ,64 cases) and the normal BMI group(18 .5≤BMI<24 .0 ,160 cases) .The differences of pregnaney outcomes between the high BMI and normal BMI PCOS pa-tients were compared .Results 1 .Basic testosterone(T) in the high BMI group was higher than that in the normal BMI group(P<0 .05) .2 .There were no statistical difference in the number of retrived oocytes ,dose of Gn ,Gn duration ,fertilization rate between the two groups(P>0 .05);the high BMI group demonstrated the higher endometrial thickness and lower good quality embryo rate than the normal BMI group(P<0 .05) .3 .There were no statistical difference in the clinical pregnancy rate and the abortion rate be-tween the two groups(P>0 .05) ,the high BMI group had the higher risk of developing gestational diabetes(GDM)than the normal BMI group(P<0 .05) .Conclusion PCOS patient with high BMI is liable to develop hyperandrogenism and increases the occurrence rate of pregnancy complication gestational diabetes mellitus (GDM ) ,but without affecting the clinical pregnancy rate .
8.Effect of musical therapy combined with sufentanil postoperative intravenous analgesia on hemodynamic changes in patient accepted lung cancer operation
Haoke TANG ; Yichun WANG ; Jingshi LIU ; Yongbei ZHU ; Xiaohong LIU ; Wenqian YANG
Journal of Chinese Physician 2013;(3):289-292
Objective To evaluate musical therapy combined with sufentanil postoperative intravenous analgesia on hemodynamic changes in patient accepted lung cancer operation.Methods Sixty lung cancer surgery patients (ASA Ⅰ-Ⅱ grade) were selected and divided randomly into musical therapy (group M; n =30) and control (group C; n =30).In group M,patients accepted music relaxation training for fifteen minutes before surgery,and music intervention for one hour at 3,7,15,19 hour after surgery.Whereas,in Group C,patients did not listen to any music during the same period.In the intensive care unit,patients were connected to a patient controlled analgesia (PCA) device.The PCA device (sufentanil 2 μg/kg,100 ml saline) was set to deliver a bolus of 2 ml,with a lockout interval of 10 min and background infusion volume of 0.5 ml/h.Hemodynamic changes,the visual analog scale (VAS) and consumption of sufentanil were recorded at the 4th,8th,12th,16th,20th and 24th hour after operation.Results SBP,DBP,HR and VAS of group M were significantly decreased compared to the group C,respectively (P <0.05),and significant difference was found in the PCA delivery frequency [group C (30.96 ± 4.00),group M (19.06 ± 3.49),t =12.39,P < 0.01] and postoperative sufentanil consumption[group C (82.65±6.19)μg,group M (52.68 ±7.07)μg,t =20.00,P <0.01].Conclusions Musical therapy combined with sufentanil postoperative intravenous analgesia was able to produce better analgesic effect in the treatment of patient accepted lung cancer operation,which decreased postoperative sufentanil consumption and effectively reduced SBP,DBP and HR,and relieved the patient's anxiety.
9.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.
10.Ultrasonic characteristics of femoral artery atherosclerotic plaques in patients with different types of coronary heart disease
Lu LIU ; Ping ZHAO ; Linghu WU ; Huizhen CHEN ; Yichun YANG
Chinese Journal of Medical Imaging Technology 2017;33(12):1824-1829
Objective To explore correlation between ultrasonic characteristics of femoral artery atherosclerotic plaques and non-ST-elevation acute coronary syndrome (NSTE-ACS).Methods Seventy-two patients with coronary heart disease (CHD) coexisting carotid artery and femoral artery plaques were divided into NSTE-ACS group (n=42) and chronic ischemic syndrome (CIS) group (n=30).The enhanced intensity (EI),volume,shape and internal echo level (EL) of plaques were detected with contrast-enhanced ultrasonic imaging and three-dimensional ultrasound combined with ultrasonic greyscale intensity quantitative analysis,and all parameters were analyzed between the two groups.Results EI and the proportion of irregular artery plaques were higher,and EL was lower in NSTE-ACS group than those in CIS group (all P<0.05).EI,EL and shape of carotid artery and femoral artery plaques were correlated with NSTE-ACS (all P<0.05).EI and EL of femoral artery plaques were risk factors for NSTE-ACS (OR=1.222,1.177,P<0.05).Areas under ROC curve of EI and EL of carotid artery plaques were 0.801 and 0.757 (both P<0.001),and those of femoral artery plaques were 0.814 and 0.774,respectively (both P<0.001).Conclusion Neovascularization,shape and internal echo are correlated with NSTE-ACS,and the correlation of femoral artery plaques with NSTE-ACS is more significant than that of carotid artery plaques.Detecting ultrasonic characteristics of femoral artery atherosclerotic plaque can provide references to early identify unstable plaque and screening high-risk patients with CHD.