1.In vitro arsenic trioxide induces apoptosis in T cells of asthmatic patients by a Bcl-2 related mechanism
Dongyun QIN ; Ren HUANG ; Tie WU
Acta Pharmaceutica Sinica 2008;43(1):35-43
This study examined the effects of arsenic trioxide on apoptosis and interleukin4 release in T cells of asthmatic patients in vitro and investigated the role of Bcl2 in the active mechanism. Tcells were isolated from asthmatic patients (n=21) and healthy controls (n=20), and then treated with arsenic trioxide and dexamethasone. Cell apoptosis was measured using fluorescence microscopy, flow cytometry and a cytochrome c ELISA kit. Interleukin4 levels in the serum and in supernatants from T cells were quantified by ELISA. Flow cytometric analysis and immunofluorescence studies were performed to determine Bcl 2 expression. Tcells of the asthmatic patients (I.e. without treatment) exhibited decelerated spontaneous apoptosis after 24 h incubation in vitro when compared to T cells of the healthy controls. With dexamethasone treatment, an increase in apoptosis of Tcells was not significantly different between both groups, irrespective of the method used. Arsenic trioxide treatment, however, significantly increased the apoptosis of T cells of the asthmatic group and showed a slight effect on the control group. In asthmatic patients, elevated levels of interleukin 4 and upregulated Bcl 2 expression were detected. Moreover, in vitro, T cells of asthmatic patients spontaneously released more interleukin4 and exhibited more Bcl 2 expression than T cells from the control group. Arsenic trioxide treatment significantly decreased interleukin4 release and downregulated Bcl 2 expression in asthmatic patients, while it only slightly affected healthy controls. Dexamethasone treatment decreased interleukin4 release in both groups examined. It did not significantly influence Bcl2 expression. These results suggest that arsenic trioxide induces T cell apoptosis and decreases interleukin4 release in T cells of asthmatic patients in vitro and that downregulation of Bcl2 expression may be an important mechanism.
2.Effects of arsenic trioxide on apoptosis and interleukin-4 release of peripheral T cells from asthmatic patients in vitro
Dongyun QIN ; Ren HUANG ; Tie WU
Chinese Journal of Pharmacology and Toxicology 2007;21(6):470-475
AIM To study the possible mechanism of the treatment of arsenic trioxide on asthma. METHODS T cells isolated from 21 asthmatic patients and 20 healthy controls were treated with arsenic trioxide (0.1 mg·L-1) or dexamethasone (5 mg·L-1),in vitro, for 24 h. Interleukin-4 (IL-4) levels in supernatants from T cells were quantified with ELISA. Cell apoptosis was measured by using fluorescence microscopy, flow cytometry and cytochrome c ELISA kit. RESULTS T cells of asthmatic patients spontaneously released more IL-4 than that of healthy controls. Arsenic trioxide significantly decreased IL-4 release of T cells from asthmatic patients, which was more obvious compared with healthy controls. Dexamethasone decreased IL-4 release in both groups. Apoptosis percentage and cytochrome c content in cytoplasm of T cells from asthmatic patients were lower than those from healthy controls. Arsenic trioxide significantly increased the apoptosis percentage and cytochrome c content in cytoplasm of T cells in the asthmatic group, and had slighter effects on that in healthy controls. Dexamathasone increased the apoptosis percentage and cytochrome c content of T cells in both groups. CONCLUSION The mechanism of the treatment of arsenic trioxide on asthma involves the induction of T cell apoptosis and decrease of IL-4 release in asthmatic patients.
3.Clinical study on mesial temporal lobe epilepsy monitored by stereotactic implantation of depth electrode into hippocampus
Liangxian SUN ; Guofeng WU ; Siying REN ; Guannan QIN ; Yuanhong MAO
Chinese Journal of Neurology 2012;45(4):233-237
Objective To observe the effects of stereotactic implanting depth electrode into the hippocampus on monitoring mesial temporal lobe epilepsy. Methods Thirteen patients with pharmacoresistant epilepsy were included in the present study.The epilcptogenic zone might be located in the hippocampus based on the symptoms and MRI data.Eight-contact depth electrode was implanted into the patients' hippocampus by stereotactic procedures to record the electroencephalogram(EEG).The duration of monitoring lasted for 24-72 hours or more,so as to be sure if the epileptogenic zone was located in the hippocampus,and to provide evidences for surgical resection of epileptic focus.Results Thirteen patients with mesial temporal lobe epilepsy underwent video electroencephalogram monitoring for 72 hours.Twentynine epileptic seizures in 7 patients were detected.Ictal EEG changes manifested as paroxysmal slow wave or spike and slow waves on the background.The epileptiform discharges started from some electrode points,and then propagated to others or the contralateral electrode. After 1-2 seconds of delay,high amplitude slow waves with the frequency of 3-4 Hz were observed on the ipsilateral scalp EEG. Clinical epileptic seizures were not detected in 6 patients during monitoring,depth electrode showed paroxysmal focal high amplitude slow wave or spike and sharp waves,scalp EEG did not find abnormality.Six of thirteen patients received surgical resection of epileptic foci,the outcome during follow-up of 3-8 months was satisfactory.Conclusions To record hippocampal EEG in patients with intractable epilepsy by stereotactic implanting depth electrode into the hippocampus might be a safe and reliable method.It might provide strong evidences for the diagnosis of patients with mesial temporal lobe epilepsy,and for the location of epilcptogenic zone.
4.Primary surgical repair of tetralogy of Fallot in symptomatic neonates and premature infants
Quansheng XING ; Qin WU ; Wei LIU ; Yueyi REN ; Qian CAO
Chinese Journal of Thoracic and Cardiovascular Surgery 2017;33(5):262-266
Objective To review our clinical experience with primary surgical repair of tetralogy of Fallot in neonates and premature infants and to discuss the timing of repair and major factors in treating this patients perioperatively.Methods From January 2012 to September 2015,a series of 19 consecutive neonates and premature infants(M/F =12/7) with tetralogy of Fallot were admitted in our center to receive surgical treatment,with a mean age of(17.3 ± 5.5) days(12-28 days) and a mean body weight of(2.9 ±0.7) kg(2.1-4.3 kg).All the 19 cases were symptomatic with cyanosis,saturation on room air 0.79 ± 0.12 (0.48-0.92),and shortness of breath.Before operation,2 cases were receiving an infusion of prostaglandin E1,5 were mechanically ventilated.7 were more than moderate anemia with hemoglobin of 55-87 g/L.All the patients received echocardiography,ECG and chest X-ray.The McGoon ratio and Nakata index were 1.09 ± 0.30 (0.8 to 1.6) and (135.5 ± 54.2) mm2/m2 (63-212 mm2/m2) respectively.18 cases received one-stage surgical repair and 1 premature infant under two-stage operation with the VSD closure after right ventricular outflow tract(RVOT) transannular patch augmentation.All the VSDs in the 18 cases were closed with continuous suture and RVOT were enlarged with autologous pericardium patch transannularly or not.Balanced and modified ultrafiltration were applied in all the patients.Patients were strictly followed up with a standard protocol focusing on right ventricular function and arrythmia.Several characteristics(e.g.time of operating,mechanical ventilation and ICU stay,complications,hospital stay time,cost of hospitalization) were compared between this group of patients and other TOF patients during the same period in our center.Results All the one-stage operations were successful.There was no mortality and major complication.Mean CPB and aortic clamping time were(111.5 ± 31.6)min (76-153min) and (73.3 ± 11.6) min (64-89 min) respectively.10 VSDs were closed with transventricular approach,6 witht transatrial appraoch and 2 with transatrial-ventricular approach.12 cases (66.7 %) had a transannular RVOT patch,4 (22.2 %) with single RVOT patch and 2 (11.1%) with transannular RVOT and left pulmonary artery patch.Atrial communication were left open in 15 cases (83.3 %).The time of mechincal ventilation and ICU stay were (123.7 ± 59.5) h (39-239 h) and (10.1 ± 3.2) days (5-19 days) respectively.All the patients were followed up for (31.8 ± 15.7) months (9-57 months).There was no mortality and major complication.ECG showed that there was no severe arrythmia except for 3 complete right branh bundle block.The latest echocardiography results showed that right heart function was normal in all the cases and RVOT grandients was less than 30mmHg except one with 35 mmHg.There were 2 cases with residual shunt less than 2 mm and 8 cases with pulmonary valvular regurgitation less than moderate degree.Compared with other TOF cases during the same period,there was no difference according to the data mentioned above except with more time of mechnical ventilation and ICU stay and more cost of hospitalization.Conclusion Primary repair of TOF can be performed safely in symptomatic neonates and premature infants,regardless of age and body weight,with favorable early and mid-term results.Excellent teamwork and accurate prenatal and postnatal diagnosis were the two major factors in yeilding good results in these patients.
5.One-stage surgical repair of interrupted aortic arch in neonates and young infants:surgical experiences, follow-up re-sults and subsequent treatments
Quansheng XING ; Yong DI ; Kuiliang WANG ; Yueyi REN ; Qin WU
Chinese Journal of Thoracic and Cardiovascular Surgery 2017;33(1):5-9
Objective To discuss one-stage surgical repair of interrupted aortic arch ( IAA) in neonates and young in-fants, summarize follow-up results and subsequent treatments.Methods From September 2010 to December 2014, a series of 38 consecutive neonates and young infants ( M/F =26/12 ) with IAA were admitted in our surgical group to receive surgical treatment, with a median age of 11 days(1 day to 5 months) and a median body weight of 4.1 kg(1.8 to 5.8 kg).IAA was type A in 24 cases, type B in 13 cases and type C in 1 case.Associated cadiovascular anomalies were common except 2 cases, including atrial septal defect(n=23), ventricular septal defect(n=36), left ventricular outlet tract obstruction(LVOTO)(n=7), anomalous left pulmonary artery from aorta(n=1), truncus arteriosus(n=1).There were 5 cases of airway stenosis in 28 cases of CT angiography and 3D airway reconstruction.All the 38 cases were admitted with differential cyanosis.36 cases were recieved one-stage surgical repair except 2 cases died before operation.35 cases of IAA associated with intracardiac anom-alies were repaired through a median sernotomy.Cardiopulmonary bypass(CPB) was performed with two canulations in ascend-ing aorta and main pulmonary artery.Selective cerebral perfusion(n=21) or circulatory arrest(n =14) was carried out with body temperature of 18℃-23℃.After the patent ductus arteriosus tissue was completely resected , a continuous end-to-end or end-to-side suturing with 7/0(8/0) prolene was performed.In 1 type B cases with expected excessive anastomotic tension, the left subclavian artery was cut off to release the aortic arch .The associated anomalies were repaired during the cooling or re-warming period.Chest close was delayed to carry out no more than 24-72 h postoperatively in 16 cases.The other one type A IAA case without intracardiac anomaly was repaired through a standard left posterior lateral incision .Patients were strictly fol-lowed up with a standard protocol.Complications such as aortic arch restenosis, new LVOTO, new airway stenosis, and so on, were specialy focused on during the follow-up period.If needed, reoperation or transcatheter intervention was applied to treat the complications.Results Two cases died before operation and another 2 died in the early period postoperatively because of pulmonary hypertension crisis and severe tracheal stenosis, respectively.Sudden death was in 1 case during the follow-up peri-od.Median CPB time was 138 min(105-208 min) and median selective cerebral perfusion or circulatory arrest time was 24 min(16-35 min) .Mechanical ventilation time was 2-25 days.Blood pressure difference between the upper and lower limbs was less than 20 mmHg in all the patients before discharge.29 cases(85.29%) was followed up for 28 months(9 -60 months).3 cases were received reoperation in 5 cases of newly detected LVOTO.One case received reoperation in the 7 preop-erative LVOTO cases because of newly detected LVOTO(blood pressure gradient more than 40 mmHg).Two cases with aortic arch restenosis received percutaneous transcatheter ballon dilation .One case with new left main bronchus stenosis after opera-tion was strictly followed up.Conclusion IAA is a rare and severe congenital heart disease.Positive surgical repair should be performed after definite diagnosis being made .Although satisfactory results can be obtained with one-stage primary operation , IAA is a kind of progressive chronic disease.New postoperative LVOTO should be focused on becasue it will need reoperation or even the third operation .
6.The impact of endothelial progenitor cells on the osteogenesis of bone marrow mesenchymal stem cell sheet-implant complex
Huan LIU ; Wei ZHOU ; Nan REN ; Qin WU ; Rui XIE ; Tian QIN ; Yimin ZHAO
Journal of Practical Stomatology 2016;32(2):155-160
Objective:To study the effects of endothelial progenitor cells(EPCs)on the osteogenesis of bone marrow mesenchymal stem cell (BMSCs)sheet-implant complex.Methods:EPCs were added to the BMSC sheets,and the expression of osteogenesis-relat-ed genes was examined by real time PCR.Cell sheets were wrapped around implants to construct cell sheet-implant complexes and the complexes were subcutaneously transplanted into SCID mice.The complexes were harvested 8 weeks after operation and observed by micro-CT and histological examination.Results:The BMSC sheet with EPCs showed higher expression of Runx2,ALP,BMP2 and VEGF in the in vitro test;higher bone volume ratio,greater amount of new bone tissue and higher expression of Runx2 and BMP2 in the in vivo test.Conclusion:EPCs can improve the osteogenesis of BMSC sheet-implant complex.
7.In vitro arsenic trioxide induces apoptosis in T cells of asthmatic patients by a Bcl-2 related mechanism.
Dong-Yun QIN ; Ren HUANG ; Tie WU
Acta Pharmaceutica Sinica 2008;43(1):35-43
This study examined the effects of arsenic trioxide on apoptosis and interleukin-4 release in T cells of asthmatic patients in vitro and investigated the role of Bcl-2 in the active mechanism. T cells were isolated from asthmatic patients (n = 21) and healthy controls (n = 20), and then treated with arsenic trioxide and dexamethasone. Cell apoptosis was measured using fluorescence microscopy, flow cytometry and a cytochrome c ELISA kit. Interleukin-4 levels in the serum and in supernatants from T cells were quantified by ELISA. Flow cytometric analysis and immunofluorescence studies were performed to determine Bcl-2 expression. T cells of the asthmatic patients (i. e. without treatment) exhibited decelerated spontaneous apoptosis after 24 h incubation in vitro when compared to T cells of the healthy controls. With dexamethasone treatment, an increase in apoptosis of T cells was not significantly different between both groups, irrespective of the method used. Arsenic trioxide treatment, however, significantly increased the apoptosis of T cells of the asthmatic group and showed a slight effect on the control group. In asthmatic patients, elevated levels of interleukin-4 and up-regulated Bcl-2 expression were detected. Moreover, in vitro, T cells of asthmatic patients spontaneously released more interleukin-4 and exhibited more Bcl-2 expression than T cells from the control group. Arsenic trioxide treatment significantly decreased interleukin-4 release and down-regulated Bcl-2 expression in asthmatic patients, while it only slightly affected healthy controls. Dexamethasone treatment decreased interleukin-4 release in both groups examined. It did not significantly influence Bcl-2 expression. These results suggest that arsenic trioxide induces T cell apoptosis and decreases interleukin-4 release in T cells of asthmatic patients in vitro and that down-regulation of Bcl-2 expression may be an important mechanism.
Adult
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Anti-Asthmatic Agents
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pharmacology
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Apoptosis
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drug effects
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Arsenicals
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pharmacology
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Asthma
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metabolism
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pathology
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Gene Expression Regulation
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Humans
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Interleukin-4
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metabolism
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Microscopy, Fluorescence
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Middle Aged
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Oxides
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pharmacology
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Proto-Oncogene Proteins c-bcl-2
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metabolism
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T-Lymphocytes
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metabolism
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pathology
8.Relationship of high-risk human papillomavirus infection and c-jun and c-fos expression in cervical carcinoma
Haohao ZHU ; Guangyu REN ; Qin WU ; Dunyong XIONG ; Ting YUAN ; Wanxia YU
Chinese Journal of Clinical and Experimental Pathology 2017;33(1):27-31
Purpose To investigate the relationship and clinical significance of high-risk human papillomavirus infection and expression of c-jun and c-fos protein in cervical carcinoma.Methods Cervista HR-HPV testing,immunohistochemical SP method were employed to detect the infection of HR-HPV,c-jun and c-fos protein in 70 cases of CSCC,60 cases of cervical intraepithelial neoplasia and 20 cases of chronic cervicitis.The correlation between c-jun and c-fos protein expression and of HR-HPV infection was analyzed.Results Of the 70 cases of CSCC,the positive HR-HPV was 69 cases,the positive rate in HR-HPV in A9 group was the highest (85%,59/69).The positive expression of c-jun and c-fos were 80% (56/70),85.7% (60/70) in 70 cases CSCC,70% (21/30) and 70% (21/30) in 30 cases of cervical high grade intraepithelial neoplasia,and 20% (6/30),23.3% (7/30) in 30 cases cervical low grade intraepithelial neoplasia,but the positive expression rates of c-jun and c-fos in the 20 cases of chronic cervicitis were 0.Expression of c-jun and c-fos in cervical cancer group was higher than that in the chronic cervicitis group and low grade intraepithelial neoplasia (P < 0.05).The expression of c-jun and c-fos was statistically significant in different groups of clinical stage and pathologic grading in the CSCC (P < 0.05).Additionally,the expression of c-jun and c-fos was positively correlated with the infection of HR-HPV in CSCC (P < 0.01).Conclusion The infection of HR-HPV has significant subtype-specific and has a positive correlation with the expression of c-jun and c-fos in CSCC,which suggests that AP-1 pathway activation after HRHPV infection may be associated with the occurrence and development of cervical carcinoma.
9.Association of FOXE1 gene polymorphism with idiopathic premature ovarian failure
Chunrong QIN ; Jilong YAO ; Zhen YUAN ; Xiaohui REN ; Jiansheng XIE ; Weiqing WU
Chinese Journal of Obstetrics and Gynecology 2015;(2):116-119
Objective To assess the influence of length of the alanine tract of forkhead box E1 (FOXE1) gene on genetic susceptibility to idiopathic premature ovarian failure (POF). Methods Totally 110 patients with idiopathic POF were recruited between February 2009 and December 2012 at the Affiliated Shenzhen City Maternity and Child Healthcare Hospital of Southern Medical University. Controls (n=110) were individuals with normal menstrual cycles, normal FSH concentrations. The polyalanine tract and flanking sequence of FOXE1 were screened using the multiplex ligation-dependent probe amplification (MLPA) technique and direct sequence technique. Results The most frequent of FOXE1 polyalanine stretch length was 14 residues in both groups. The length of FOXE1 polyalanine reported in this study varied from 12 to 16 alanines, and three variants of FOXE1-polyalanine length, containing 12, 14, or 16 alanine residues, and 5 different genotypes were identified. The most common genotypes were 14/14 homozygote, occurring with the frequency of 81.8% (90/110) in the POF group, while 96.4% (106/110) in control subjects, respectively. The incidence of 14/14 genotypes of FOXE1-polyalanine was significantly lower in patients with POF (χ2=119.730, P=0.001) in comparison to the controls. There were significantly higher frequencies of the 16/16 genotypes in cases with POF [10.0% (11/110) versus 0; χ2=3.403, P=0.001], as compared with the controls. The FOXE1 14 alanine allele was significantly less common in the POF patient group than the controls [84.5% (186/220) versus 98.2% (216/220); χ2=25.923, P=0.001]. The FOXE1 16 alanine allele was significantly more common in the POF patient group than the controls [12.7% (28/220) versus 1.8% (4/220); χ2=19.412, P=0.001]. Conclusions The polymorphism of the polyalanine tract of FOXE1 gene have a certain relevance for the genetic aetiology of idiopathic POF.
10.Relationship between perfusion mode of carotid plaque in CEUS and ischemic stroke in transient ischemic attack patients
Zhenzhou LI ; Lijie REN ; Yufeng SHAO ; Shenghua CHEN ; Yu QIN ; Xiaoyun GUAN ; Xinyin WU
Chinese Journal of Medical Imaging Technology 2017;33(4):534-538
Objective To evaluate the relationship between the perfusion mode of neovascularization of carotid plaque in CEUS and the ischemic stroke in transient ischemic attack (TIA) patient.Methods A total of 73 TIA patients according to the inclusive criteria were enrolled.All the patients underwent routine carotid ultrasonic examination.And 61 patients with plaque thicker than 2.5 mm in carotid bifurcation underwent CEUS and follow-up for at least 18 months.All the patients were divided into recurrent and non-recurrent groups.Logistic regression analysis were performed to detect the risk factors for incurrence of ischemic stroke or recurrence of TIA in 18 months.Results There were statistical differences between 2 groups in hypertension,diabetes,hyperlipemia,smoking history,family history of stroke,medication compliance,two-dimensional ultrasound and CEUS characteristics (all P<0.05).Multivariate Logistic regression analysis showed that all the factors correlated with the recurrency,from big to small order were the CEUS characteristics of carotid plaque,hypertension,medication compliance,diabetes,two-dimensional ultrasound characteristics of carotid plaque.Conclusion CEUS could evaluate the perfusion mode of neovascularization in carotid plaques.For TIA patients,CEUS could predict the incurrence of ischemic stroke or recurrence of TIA,which can guide TIA patients targeted prophylaxis of them.