1.Effect of triiodothyronine(T3) on apoptosis of endothelial cells and interventional study with osteoprotegerin
Chinese Journal of Endocrinology and Metabolism 2013;29(12):1056-1060
Objective To explore the effect and mechanism of osteoprotegerin on apoptosis in human umbilical vein endothelial cells(HUVECs) induced by triiodothyronine(T3) with different concentrations.Methods HUVECs were cultured in control group (0 nmol/L T3),low-concentration group (0.1 nmol/L T3),physiologicalconcentration group(1 nmol/L T3),high-concentration group(10 nmol/L T3) with OPG for 48 h.The cell apoptosis was measured by cytometry and Hoechst 33258.The expressions of p-IκKβ,lκKβ,p-TSC2,TSC2,p-S6K,S6K,p-AKT,AKT,Bcl-2,and Bax were analyzed by Western blot.Results (1) After OPG pretreatment and being cultured in control group、low-concentration group and high-concentration group,the HUVEC apoptosis was decreased significantly(P<0.05) as compared with groups without OPG pretreatment.There was no difference in physiological concentration group before and after intervention of OPG.(2) The expression of p-IκKβ,p-S6K,and Bax in other groups were higher than those in physiological concentration group ; however,the expressions of p-TSC2,p-AKT,and Bcl-2 were lower than those in physiological concentration group(P<0.05).After OPG pretreatment in control group,low-concentration group,and high-concentration group,the expressions of p-IκKβ,p-S6K,and Bax decreased significantly (P<0.05)and the expression of p-TSC2,p-AKT,and Bcl-2 increased significantly (P< 0.05) ; there were no differences in the expressions of p-IκKβ,p-S6K,p-TSC2,p-AKT,Bcl-2,and Bax in physiological concentration group before and after intervention of OPG.Conclusions Low and high concentrations of T3 increase apoptosis of HUVECs by way of activation of IκKβ/mTOR pathway.Osteoprotegerin is able to protect HUVECs from apoptosis induced by low and high concentration of T3 via the way of inhibiting the IκKβ/mTOR pathway.
2.Hexokinase-Ⅱ role in tumor growth and targeting therapy
Haohua WANG ; Xiuxing CHEN ; Guifang GUO
Journal of International Oncology 2017;44(3):213-216
The energy for tumor cells mainly derives from the aerobic glycolysis,that is,the Warburg effect,which also provides a large amount of precursor substances for the growth of tumor cells.Hexokinase-Ⅱ (HK-Ⅱ),highly expressed in tumor tissue,is the rate-limiting enzyme of glycolysis and closely related to the energy metabolism of tumor.Recent studies have showed that HK-Ⅱ not only mediates Warburg effect,but also promotes tumor proliferation by inhibiting tumor cell apoptosis and regulating autophagy.It has been confirmed that blocking HK-Ⅱ gene expression and inhibiting HK-Ⅱ with small molecule inhibitor can kill tumor cells in many kinds of cancer.Agent targeting HK-Ⅱ may become a new generation of targeted drugs.
3.Application of intravital fluorescence microscopy in the observation of the changes of hepatic microcirculation in rat with hepatic cirrhosis and portal hypertension
Liangshuo HU ; Haohua WANG ; Jianhua WANG ; Yi LYU
Chinese Journal of Digestive Surgery 2014;13(4):286-290
Objective To investigate the value of intravital fluorescence microscopy in the observation of the changes of hepatic microcirculation in the rat model with hepatic cirrhosis and portal hypertension.Methods Seventy male SD rats were selected.According to the random number table,40 SD rats were randomly divided into the sham operation group,bile duct ligation (BDL) 2 weeks group,4 weeks group and 6 weeks group,there were 10 rats in each group,and the hepatic microcirculation of the rats was observed with intravital fluorescence microscope; the remaing 30 SD rats were randomly divided into the normal saline (NS) group,endothelin-1 (ET-1) group and the S-nitrosoglutathion (GSNO) group at 4 weeks later after the establishment of BDL model.The changes of hepatic microcirculation of the 3 groups were observed.All data were analyzed using the one-way analysis of variance (ANOVA) or paired samples t test.Results Nine rats died in the BDL model groups,and the survival rate was 85.0% (51/60).All rats in the sham operation group were survived.The hepatic sinusoid diameters were decreased as time passed by.The hepatic sinusoid diameters of the BDL 2 weeks group,4 weeks group and 6 weeks group were (13.6 ± 1.0) μm,(8.8 ± 0.7) μm and (8.0 ± 0.5) μm,respectively,which were significantly shorter than (17.4 ± 1.0) μm of the sham operation group (t =5.86,18.24,15.57,P < 0.05).The hepatic sinusoid densities of the BDL 2 weeks group,4 weeks group and 6 weeks group were (6.8 ±0.8)/ 200 μm,(4.3 ± 1.8)/200 μm and (4.0 ± 1.2)/200 μm,which were significandy lesser than (8.8 ± 0.5)/200 μm (t =3.25,2.77,2.12,P < 0.05).At 15 minutes after injection of NS,the hepatic sinusoid diameter of the NS group was (7.2 ± 1.2) μm,which was significantly different from (6.9 ± 0.5) μm before injection of NS (t =0.89,P > 0.05) ; the hepatic sinusoid density of the NS group before and after injection of NS were (6.6 ± 0.4) / 200 μm and (6.8 ± 1.4)/200 μm,with no significant difference(t =1.12,P >0.05).At 15 minutes after injection of ET-1,the hepatic sinusoid diameter of the ET-1 group was (5.4 ±0.5) μm,which was significantly different from (7.9 ± 0.6) μm before injection of ET-1 (t =7.39,P < 0.05) ; the hepatic sinusoid density of the ET-1 group before and after ET-1 injection were (5.8 ± 1.2)/200 μm and (5.4 ± 1.8)/200 μm,with no significant difference(t =0.84,P >0.05).At 15 minutes after injection of the GSNO,the hepatic sinusoid diameter of the GSNO group was (11.4 ± 1.3) μm,which was significantly different from (7.5 ± 1.7) μm before injection of GSNO (t =5.95,P < 0.05) ; the hepatic sinusoid density of the GSNO group before and after GSNO injection were(5.6 ± 0.8)/200 μm and (6.4 ± 1.6)/200 μm,with no significant difference (t =0.54,P > 0.05).Conclusions The changes of hepatic microcirculation observed under intravital fluorescence microscope could reflect the progress of hepatic cirrhosis,and the changes of hepatic sinusoid diameters caused by drugs could be dynamically monitored under the intravital fluorescence microscope.
4.Image characteristics of chest schwannoma in coincidence 18F-FDG SPECT studies
Lihua WANG ; Haohua TENG ; Bei LEI ; Cheng CHANG ; Wenhui XIE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2016;36(3):237-241
Objective To analyze the image characteristics of chest schwannoma in coincidence 18FFDG SPECT studies,and to evaluate its prospective diagnostic function on chest schwannoma.Methods Four cases confirmed as schwannoma by surgery and pathology were enrolled in this retrospective study.Enhanced CT and coincidence 18F-FDG SPECT studies were performed before surgery.Imaging characteristics for the diagnosis of chest schwannoma were summarized.Results Tumors were totally removed by surgery.The histological diagnosis of schwannoma was confirmed by pathological,HE and immunohistological staining examination (positivity for the S-100 protein and vimentin),including 1 case of malignant schwannoma and 3 cases of benign.Four cases all showed high uptake of 18F-FDG.The uptake in malignant schwannoma was much higher than that in benign schwannoma.Benign schwannomas were noninvasive masses and mainly showed compression symptoms,with obvious lobulation and distinct borders.Malignant schwannoma was invasive masses.Conclusions 18 F-FDG coincidence SPECT is of limited value as a prospective diagnostic imaging technique for the identification of benign schwannoma from malignant schwannoma.But it could play an important role in the staging,restaging,and post-therapy follow-up of schwannoma.
5.Protective effect and its mechanism of osteoprotegerin on human umbilical vein endothelial cells cultured with high glucose
Lin XIANG ; Guangda XIANG ; Haohua WANG ; Jing DONG
Chinese Journal of Endocrinology and Metabolism 2013;(6):525-530
Objective To explore the effect and its mechism of osteoprotegerin (OPG) on human umbilical vein endothelial cells(HUVECs) induced by high glucose.Methods (1) The cultured HUVECs were treated with normal glucose(5.5 mmol/L),high glucose(33 mmol/L),high glucose + OPG(0.5,1,and 2 μg/ml)as well as mannitol(5.5 mmol/L glucose+27.5 mmol/L mannitol) for 48 h,respectively.Flow cytometry assay and Hoechst 33258 staining were used to detect the cell apoptosis.The expression levels of Bcl-2 and Bax protein were measured by western blot analysis.(2) The cultured HUVECs were treated with normal glucose,high glucose,high glucose + OPG (2 μg/ml OPG),high glucose + rapamycin(10 ng/ml rapamycin) as well as high glucose + rapamycin + OPG for 24h,respectively.The expression levels of S6K,p-S6K,4EBP1 and p-4EBP1 protein were measured by western blot analysis.(3)The cultured HUVECs were treated with normal glucose,high glucose,high glucose + OPG(2 μg/ml)for 24 h,respectively.The expression levels of tuberin and p-tuberin protein were measured by western blot analysis.Results (1) Compared with normal glucose group,the apoptosis of HUVECs and the expression level of Bax was dramatically increased,and the expression of Bcl-2 was decreased significantly in high glucose group (P<0.05).The apoptosis of HUVECs and the expression level of Bax in high glucose + OPG group was significantly lower than that in high glucose group,which was still higher than that in normal glucose group (P< 0.05).and the expression of Bcl-2 in high glucose + OPG group was significantly higher than that in high glucose group,which was still lower than that in normal glucose group (P<0.05).There was no statistically difference between hyperosmolar control group and normal glucose group.(2) Compared with normal glucose group,the expression levels of p-S6K and p-4EBP1 were increased markedly in high glucose group(P<0.05).The expression levels of p-S6K and p-4EBP1 in high glucose + OPG group were significantly lower than that in high glucose group,which were still higher than that in normal glucose group(P<0.05).No significant difference was found between high glucose + OPG group and high glucose + rapamycin group.(3) Compared with normal glucose group,the expression level of p-tuberin was increased markedly in high glucose group (P < 0.05).The expression level of p-tuberin in high glucose + OPG group was significantly lower than that in high glucose group,which was still higher than that in normal glucose group (P <0.05).Conclusions It suggests that the protective effect and mechanism of OPG on HUVECs cultured with high glucose may be association with tuberin/mTORC1 pathway.
6.Evaluation of left and right ventricular function by real-time three-dimensional echocardiography in patients with heart transplantation
Cuizhen PAN ; Chunsheng WANG ; Xianhong SHU ; Haiyan CHEN ; Haohua YAO ; Hao CHEN
Chinese Journal of Ultrasonography 2011;20(7):553-557
Objective To evaluate left and right ventricular function by real-time three-dimensional echocardiography in patients with heart transplantation.Methods Fourteen patients with heart transplantation ( rejection)[12 male,2 female,mean age (49.21±17.91)],twenty four patients with heart transplantation (no rejection) [21 male,3 female,mean age (40.11±12.57)],and fifty one subjects with normal left ventricular function [26 male,25 female,mean age (43.69±14.81) ] were examined by Philips iE33 with a X3-1 probe.Results Right ventricular stroke volume (RVSV) and right ventricular ejection fraction (RVEF) in heart transplantation (including no rejection and rejection) was reduced compared with subjects with normal heart function (all P<0.05),but right ventricular end-diastolic volume (RVEDV) and right ventricular end-systolic volume (RVESV) were no significantly different between heart transplantation and subjects with normal heart function (all P>0.05),but the volume and function of right ventricle were no significantly different between rejection heart transplantation and no rejection heart transplantation.Parameter index of 17 segment including standard deviation (SD) and maximum difference(Dif) of 16,12 and 6 segment time to minimal systolic volume(Tmsv 16-SD,Tmsv 16-Dif,Tmsv 12-SD,Tmsv 12-Dif,Tmsv 6-SD,Tmsv 6-Dif),and the percent of SD and maximum difference 16,12 and 6 segment time tominimal systolic volume [Tmsv 16-SD(%),Tmsv 16-Dif(%),Tmsv 12-SD(%),Tmsv 12-Dif(%),Tmsv 6-SD(%),Tmsv 6-Dif(%)] was significantly higher in patients with heart transplantation (rejection) than that in subjects with normal heart function and in patients with heart transplantation (no rejection)[except Tmsv 16-SD and Tmsv 16-SD(%),other P<0.05],however,there was no significantly different between heart transplantation (no rejection) and subjects with normal heart function(all P>0.05).But also average,maximum and minimum value of excursion in three groups was no significantly different (all P>0.05).Conclusions Real-time three-dimensional echocardiography can rapidly and acurately evaluate left and right ventricular function in patients with heart transplantation.
7.Investigation and Analysis on Dysmenorrhea and Constitution of Students in Adolescent Age
Xiaojing GAO ; Chunjuan XU ; Ying AI ; Qichang BAO ; Jing WANG ; Haohua XINAG
International Journal of Traditional Chinese Medicine 2008;30(6):419-420
Objeclive To explore relationship between TCM constitution and primary dysmenorrhea of female students in adolescent age,and to observe clinical effect of treating dysmenorrhea of students whose constitution tends toward Qi-deficiency and Yang-deficiency with wanning meddian therapy.Methods Relationship between TCM constitution and dysmenorrhea was performed in 789 students by questionnaire.Results Students with dysmenorrhea accounted for 50.3%,in which students with mild constitution accounted for 70.2%,and students with constitution tending toward Qi-deficiency and Yang-deficiency accounted for 80%.Conclusion Dysmenorrhea is associated with constitution.Warming meridian therapy can adjust constitution tending toward Qi-deficiency and Yang-deficiency.
8.Evaluation of left ventricular systolic and twist function in patients with heart transplantation using ultrasound speckle tracking imaging
Cuizhen PAN ; Hao CHEN ; Xianhong SHU ; Minmin SUN ; Shijie ZHU ; Haohua YAO ; Chunsheng WANG
Chinese Journal of Ultrasonography 2008;17(11):930-933
Objective To investigate the feasibility of ultrasound speckle tracking imaging(STI)in assessing left ventricular(LV)systolic and twist function in patients with heart transplantation.Methods Nine patients with heart transplantation and 10 subjects with normal LV function were examined by GE Vivid 7 with a M3S probe.Eighteen regional peak systolic strain and displacement in longitudinal,radial,circumferential,and 18 regional degree of rotation were measured respectively.Results The segmental regional peak systolic strain and displacement were less than those in subjects with normal LV function(P <0.05),but segmental regional degree of rotation was more than that in subjeets with normal LV function (P<0.05).Conclusions STI may provide a noninvasive,simple and quick tool for evaluation of left ventricular systolic and twist function in patients with heart transplantation.
9.Relationship of Platelet Aggregation and Inflammatory Factors in Patients With Coronary Heart Disease
Xin QI ; Keqiang LIU ; Min WANG ; Haohua YIN ; Chunjie ZHAO ; Songsong LI
Chinese Circulation Journal 2009;24(3):178-181
Objective:To observe the correlation of platelet activation and the inflammatory factors in patients with coronary heart disease (CHD).Methods:A total of 150 patients with CHD were divided into three groups according to the guideline of ACC/AHA:Stable angina pectoris (SAP) group (n=47,aspirin 100 mg/d); Unstable angina pectoris(UAP) group (n=50,aspirin 100 mg/d+Dalteparin 5000 U Q12 h); Acute myocardial infarction (AMI) group (n=53,aspirin 100 mg/d+Dalteparin 5000 U Q12 h+Plavix 75 mg/d).53 healthy adults served as the Control group.The fast blood sugar,lipid,platelet count,platelet aggregation of plasma,fibrinogen,high sensitivity C reactive protein (hs-CRP) of plasma,and 11-dehydro thromboxane B_2 (11-DH-TXB_2) of urine were detected upon patients' admission.Results:The level of plasma hs-CRP in groups of SAP,UAP and AMI(4.25±2.95 mg/l,7.61±6.11 mg/l,15.46±8.22 mg/l)were significantly higher than that in Control group(2.07±1.28 mg/l,P<0.05).The max rate of platelet aggregation induced by ADP in groups of UAP and AMI were significantly higher than that in Control and SAP groups(74.35±8.91%,73.88±8.35% vs.66.22±7.51%,68.67±6.87%,P<0.05).There were significant differences in the max rate of platelet aggregation induced by arachidonic acid (AA) and 11-DH-TXB_2 of urine in different groups (P<0.05).The level of plasma hs-CRP in all patients with CHD were significantly positively correlated with the max rate of platelet aggregation induced by ADP (r=0.473,P=0.000),AA(r=0.434,P=0.000) and 11-DH-TXB_2 of urine (r=0.554,P=0.000).Conclusion:There were significant relationship between the levels of plasma hs-CRP,11-DH-TXB_2 and the max rate of platelet aggregation,which indicating inflammation might induce platelet aggregation in CHD patients.
10.Evaluation of left ventricular torsion and segmental function by speckle tracking imaging and real-time three dimensional echocardiography in patients with heart transplant
Cuizhen PAN ; Xianhong SHU ; Minmin SUN ; Haohua YAO ; Hao CHEN ; Chunsheng WANG
Chinese Journal of Ultrasonography 2010;19(8):649-654
Objective To evaluate left ventricular torsion and systolic function of the segment by speckle tracking imaging(STI) and real-time three-dimensional echocardiography(RT-3DE) in patients with heart transplantation. Methods Twenty patients with heart transplantation and twenty subjects with normal left ventricular function were examined by Philips iE33 with a X3-1 probe and GE Vivid 7 with M4S probe.Results There were two subjects(100% ) with clockwise rotation in control group patients, but eight patients (40 % ) with clockwise rotation in heart transplantation group. And heart transplantation group were divided into two sub-groups (group A with counterclockwise rotation and group B with clockwise rotation) based on the direction of rotation. In apical level,the systolic peak of the angle of rotation of anterior septum,posterior wall,inferior wall, posterior septum in group A was less than that of control group( P <0.05), all segmental systolic peak of the angle of rotation in group B was reduced compared with control group( P <0. 05),however all segmental systolic peak of rate of rotation in group A and group B was not significant different compared with control group ( P >0. 05) ,all segmental diastolic peak in early and late of rate of rotation in group B was obviously higher than that in control group and group A ( P <0. 05), while all segmental diastolic peak in early and late of rate of rotation in group A was not significant different compared with control group( P >0.05). The displacement and the parameter index of 17 segment time to minimal systolic volume in group A and group B were not significant different compared with control group( P >0. 05), but left ventricular angle of torsion was decreased in group B compared with control group and group A( P <0.05). Conclusions STI and RT-3DE can rapidly evaluate function of left ventricular torsion and function of segmental systole and systolic synchrony in patients with heart transplant.