2.The role of postmastectomy radiotherapy in different molecular subtypes of breast cancer patients with T1 - T2 and one to three positive axillary nodes
Hao WANG ; Yangkun LUO ; Jie WANG ; Yin PENG ; Hao WEN ; Weidong WANG ; Jinyi LANG
Chinese Journal of Radiation Oncology 2011;20(5):397-401
ObjectiveTo analyze the role of postmastectomy radiotherapy in different molecular subtypes of breast cancer patients with Stage T1 -T2 and one to three positive axillary nodes. MethodsA total of 436 breast cancer patients with T1 -T2 and one to three positive axillary lymph nodes treated with mastectomy and axillary dissection were retrospectively analyzed. Patients were grouped as the following four subtypes:Luminal A, Luminal B, Her2+ and triple-negative. The local recurrence (LR), distant metastasis ( DM ), disease free survival (DFS) and overall survival (OS) rates were compared between paitents with or without radiotherapy in univariate analyses. Multivariate analyses for LR were performed. Results The follow-up rate was 86. 0%. In patients with Luminal A subtype, radiotherapy decreased the 5-year LR rate (4.6% vs 15.8% ,x2 =5.74,P=0.017) but had no influences on DM, DFS or OS rates (17.2% vs 19.7%,x2 =0. 17,P=0.682;77.0% vs 67. 1% ,x2 =1.99,P=0. 158 or87.4%:85. 5% ,x2 =0. 12,P=0. 733 ). In patients with Luminal B subtype, radiotherapy decreased the 5-year LR rate (3.7% vs 12. 1%,x2 =4. 13, P =0. 042), increased DFS and OS ( 84. 0% vs 57.6% ( x2 =14.61, P =0. 000) and 91.4% vs 70. 7% ( x2 =11.87, P =0. 001 ), but had no influence on DM ( 12. 3% vs 22. 2%, x2 =2. 97, P =0. 085).In patients with Her2+ subtype, radiotherapy decreased the 5-year LR rate (5. 6% vs 31.0% ,x2 =4. 31,P=0. 035) , increased DFS (61. 1% vs 13. 8% ,x2 =11.44,P=0.001 ) ,but had no influence on DM and OS (27.8% vs 41.4%, x2 =0. 89, P =0. 345 and 66. 7% vs 48. 3%, x2 =1.52,P =0. 218 ). In patients with triple-negative subtype, radiotherapy had no influence in LR, DM, DFS or OS (8. 7% vs 26. 1% ,x2 =2.42,P=0.120;39.1% vs47.8%,x2=0.35,P=0.552;52.2% vs 26.1% , x2 =3. 29, P =0. 070 or 65.2% vs 56. 5% ,x2 =0. 37 ,P =0. 546). Tumor size and radiotherapy were independent prognostic factors for LR rate in multivariate analyses ( x2 =4. 76, P =0. 029 and x2 =8.06, P =0. 005 ). ConclusionsFor patients with stage T1 -T2 and one to three positive axillary nodes, patients with all molecular subtypes except triple-negative can benefit from postmasteetomy radiotherapy.
5.Effects of angiotensin converting enzyme inhibitor on expression of transforming growth factor β1 and β1-integrin in glomerular mesangial cells induced by lipopolysacchatide
Zhihong HAO ; Ying DENG ; Li YU ; Lina WANG ; Jie WEN
International Journal of Pediatrics 2011;38(6):628-631
Objective To observe the effects of one kind of angiotensin converting enzyme inhibitor (ACE1) drugs fosinopril (FOS) on transforming growth factor β1 (TGF-β1)and β1- integrin( Itg-31 ) expression in rat glomerular mesangial cells (GMC)induced by lipopolysacchatide (LPS).Methods We established the cultured glomerular mesangial cells of rat in vitro and passages 3 ~ 10 of cells were used in the experiment after identification.The experiment included the following groups:Control group,LPS induced group (LPS group) and FOS intervened group.According to the different concentrations of FOS,FOS intervened group was divided into high,middle and low dose FOS groups,which were FOS1 group,FOS2 group and FOS3 group respectively.The changes of TGF-β1 protein secretion was detected by the enzyme-linked immunosorbent-assay; The changes of TGF-β1 and Itg-β1 mRNA expression was detected by quantitative real-time RT-PCR.Results (1) TGF-β1protein secretion in rat GMC at 6h,12h,24h three time points:They were 958.55 ± 34.67 ( ng/L),1052.05 ±48.59( ng/L),1166.06 + 35.39 (ng/L) respectively in Control group.They were 1342.12 + 39.87 ( ng/L),1432.31 + 39.33 (ng/L) and 1 537.77 + 43.79 (ng/L) respectively in LPS group,which were higher significantly than those in Control group ( all P < 0.01 ).They were 779.58 ± 48.64 ( ng/L),878.33 ± 29.50 (ng/L) and 962.57 ±31.94( ng/L) in FOS1 group,989.311±73.56(ng/L),1073.29±66.89(ng/L) and 1210.75 ±61.68(ng/L) in FOS2 group,1 253.78 ±45.32( ng/L),1 348.18 ±45.81 (ng/L) and 1450.06 ±46.24( ng/L) in FOS3 group respectively,which were lower significantly in all FOS intervened groups than that in LPS group (all P<O.01).(2)TGF-β1 mRNA expressions in rat GMC at6h,12h,24h three time points were higher significantly than that in Control group.TGF-β1 mRNA expressions were lower significantly in all FOS intervened groups than that in LPS group.( 3 ) Itg-β1 mRNA expressiones in rat GMC at 6h,12h,24h three time points were higher significantly than that in Control group.Itg-β1 expressions were lower significantly in all FOS intervened groups than that in LPS group.Conclusions LPS can induce the increase of TGF-β1 secretion and mRNA expression.FOS can inhibit the TGF-β1 secrection and mRNA expession in GMC as dose-dependent manner,at the same time down regulated the Itg-β1 mRNA expression iuduced by LPS.All above supply the theoretical evidence for the renal protection of FOS by non-hemodynamics mechanism.
6.SYNTHESIS AND BIOLOGICAL ACTIVITIES OF NEW 5-HT2A SELECTIVE LIGANDSN-SUBSTITUTED-PIPERIDINYL4-PHENYLTHIOETHER AND SULFONE DERIVATIVES
Hao WANG ; Ren WEN ; Lei HUANG ; B.innis ROBERT ; Pingzhong TAN
Acta Pharmaceutica Sinica 2001;36(4):274-277
AIM A series of 4-piperidinylthioether and sulfone derivatives of 4-[1-hydroxy-1-(2,3-dimethoxyphenyl) methyl]-N-2-(4-fluorophenylethyl) piperidine (MDL 100907) were synthesized in order to find new 5-HT2A selective ligands. METHODS Title compounds 2a-2c were synthesized from 2,3-dimethoxythiophenol and tested for their affinities to 5-HT2A, 5-HT2C, 5-HT6 and 5-HT7 receptors and some other nervous transmitter receptors in vitro. RESULTS Compounds 2a-2c are new compounds. The results of the binding assay demonstrated that they have relatively high selectivity for 5-HT2A receptor in vitro. CONCLUSION Some sulfur containing analogues of MDL 100907 showed selective affinity to 5-HT2A receptor and are worth further study.
8.Clinical Observation of Ziprasidone Combined with Olanzapine in the Treatment of Refractory Schizophre-nia in Elderly Patients
Jinyu HAO ; Binhua CHEN ; Tianxing QIN ; Lirong WANG ; Jiangang WEN
China Pharmacy 2015;26(33):4652-4654
OBJECTIVE:To observe the efficacy and safety of olanzapine combined with ziprasidone in the treatment of refrac-tory schizophrenia in elderly patients. METHODS:120 elderly patients with schizophrenia were randomly divided into control group and study group. Control group was orally treated with Olanzapine tablet 10-20 mg,once a day;study group was orally treat-ed with Ziprasidone hydrochloride capsule 80-120 mg,twice a day+Olanzapine tablet(the usage was the same as control group). The clinical efficacy in 2 groups was evaluated after 2 weeks,PANSS score,FPG,2 h PG,TC,TG,HDL-C,LDL-C,body weight, BMI before and after treatment and incidence of adverse reactions were observed. RESULTS:There were no significant difference in the total efficacy and incidence of adverse reactions between 2 groups(P>0.05). After treatment,the PANSS scores at different time point in 2 groups were significantly lower than before,and 12 weeks<8 weeks<4 weeks<2 weeks,the differences were sta-tistically significant(P<0.05),however,there was no significant difference between 2 groups(P>0.05). There were not signifi-cant differences in the indexes of blood glucose and lipid,body mass and BMI in study group before and after treatment (P>0.05);after treatment,the blood glucose after 8 and 12 weeks and LDL-C,TG,TC,body mass and BMI after 4,8 and 12 weeks in control group were significantly higher than before and study group same time,the HDL-C was significantly lower than before and research group,the differences were statistically significant(P<0.05). CONCLUSIONS:The efficacy and safety of both olan-zapine combined with ziprasidone and olanzapine alone in the treatment of refractory schizophrenia in elderly patients is similar, however,it is better than olanzapine alone in terms of controlling blood glucose and lipid.
9.Establishment of liver transplantation model with improved two-cuff in rat
Hao WANG ; Xiaowei WEN ; Huanzhi CHEN ; Yonghong DONG ; Jun XU
Cancer Research and Clinic 2016;28(4):262-265
Objective To build rat orthotopic liver transplantation model and use this model as an experimental animal model for further research about liver transplantation.Methods Based on the classic two-cuff technique,a variety of skills were integrated,such as abdominal aorta perfusion first before ligation,suprahepatic inferior vena cava single continuous suture,preoperative and postoperative rehydration,hepatic portal vein and infrahepatic vena cava blocked by mosquito's haemostatic forceps.At last,the postoperative survival rates of 2 days and 2 weeks were recorded.Results Donors' operation time was (35±2) min,cuffing time was (7.0±1.5) min,receptors' operation time was (80±15) min,anhepatic phase was (21±3) min.The 2-day survival rate was 92 % (46/50) and 2-week survival rate was 86 % (43/50).Conclusion To some extent,the improved methods can not only reduce the difficulty of orthotopic liver transplantation operation,but also to create a uniform,stable and reliable orthotopic liver transplantation model.
10.Establishment of a rat model of atrioventricular block by chemical ablation
Xuemei WANG ; Mei MA ; Chun ZHANG ; Xi SHOU ; Hao WEN
Journal of Medical Postgraduates 2014;(4):378-381
Objective Preparation of a stable and reliable atrioventricular blockage ( AVB) animal model is of great im-portance to anti-arrhythmic drugs and biological engineering research .The aim of the article was to establish a rat model of AVB in-duced by chemical ablation, providing an effective animal model for the development of new drugs . Methods 60 adult SD rats were randomly divided into 4 groups(n=15): normal saline (NS) group, Verapmil (Ver) group, chemical ablation group 1 and chemical ablation group 2.0.9%NaCl (5 mg/kg) was injected into caudal vein of each rat in NS group .Verapmil (5 mg/kg) was injected into the caudal vein in Ver group.Anhydrous ethanol(50μL)was injected into atrioventricular groove area in chemical abla-tion group 1.Anhydrous ethanol(50μL) was injected into atrioventricular node area in chemical ablation group 2.The electrocardio-grams of the rats were examined by electrophysiological recorder.HE staining and Connexin 43 (CX43) immunohistochemical tech-nique were applied to atrioventricular junctions of the rats . Results A rat model of AVB was successfully established .Compared with NS group([45 ±2.24]per field of view), there was a significant decrease in the CX43 expressions of chemical ablation group 1 and group 2 ([15.20 ±2.23]per field of view, [22.10 ±4.70]per field of view)(P<0.05).Concerning NS group and Ver group, myocyte tissues of the atrioventricular nodal region were detected to remain in order without obvious changes and the expres-sion of CX43 immunoreactive protein was obvious under light microscope.As to chemical ablation group 1 and group 2, myocyte tissues were in degenerative necrosis and the expression of CX43 im-munoreactive protein was in lighter staining.Compared with Ver group, the incidence rate(73.3%, 60.6%) and the mortality rate (33.3%, 26.7%)of third-degree AVB decreased remarkably(P<0.05). Conclusion Chemical ablation can be induced to estab-lish a stable and reliable rat model of AVB , providing an effective
animal model for the research and development of new anti-arrhythmic drugs.