3.RNAi-silenced human Bmi-1 gene inhibits proliferation of human leukemia cell line K562
Yong ZHU ; Yide HU ; Zhonghua HU
Journal of Third Military Medical University 2003;0(09):-
Objective To explore the silence of B-cell specific Moloney murine leukaemia virus insertion site 1(Bmi-1)by RNA interference on the proliferation of human leukemia cell line K562 and its mechanisms.Methods Small interfering RNA(siRNA)targeting Bmi-1 gene was designed and double-stranded siRNA was chemically synthesized.After double-stranded siRNA was transfected into K562 cells with Lipofectamine 2000,the proliferation of K562 cells was detected by MTT colorimetry,cell cycle was determined by flow cytometry,and the expression of Bmi-1 and P16 were analyzed by Western blotting.Results The siRNA targeting human Bmi-1 gene effectively prolonged the double time of K562 cells,increased the percentage of cells at G1 phase,and the expression of Bmi-1 was significantly down-regulated but the expression of P16 was up-regulated.Conclusion The siRNA targeting human Bmi-1 gene inhibits the proliferation of K562 cells,and up-regulates the expression of P16 in the cells.
4.Serum metabolite changes of aged rats with post-anesthesia cognitive dysfunction
Rong HU ; Jianbin TONG ; Zhonghua HU
Journal of Chinese Physician 2016;18(6):861-864
Objective To explore the effects of isoflurane on blood plasma metabolites (BPM) and its correlation with cognitive dysfunction.Methods Thirty female Sprague-Dawley (SD) rats were randomly divided into two groups:rats in the control group (n =10) received 80% oxygen for 2 hours (h);and rats in the isoflurane-treated group (n =20) were anesthetized with isoflurane and 80% oxygen for 2 h.Cognitive functions were examined using a Y-maze test to explore the learning times of rats.The level of blood plasma metabolites was detected through gas chromatography-mass spectrometry (GCMS).Results The learning times of rats in the isoflurane-treated group was more than the learning times of rats in the control group [(70.75 ± 15.30) vs (45.40 ± 11.21),P < 0.05].D-fructose,arabinofuranose,n-butylamine,and inositol significantly increased (P < 0.05),respectively.Whereas,L-analine and L-proline significantly decreased (P < 0.05) in isoflurane-treated rats when compared to those in the control rats (P < 0.05).Moreover,plasma concentrations of d-fructose,arabinofuranose,n-butylamine,inositol,and L-proline were positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats.Conclusions Changes of plasma concentrations of inositol,and d-fructose in aged rats are useful in predicting the occurrence and progression of post-anesthesia cognitive dysfunction.
5.Application of Wheelchair for Spinal Cord Injury (review)
Jianlong ZHUANG ; Yuming WANG ; Zhonghua HU
Chinese Journal of Rehabilitation Theory and Practice 2015;21(4):449-452
The wheelchair is one of the main assistive appliance for patients with spinal cord injury. With the improvement of material and technique, it is more complicated to select the wheelchair and wheelchair seat equipment. The researches in recent years involved application of wheelchair for patients with spinal cord injury, including the cushions and other structures, which were reviewed in this article.
6.Primary breast lymphoma:an analysis of 36 cases
Bo LIU ; Zhonghua TANG ; Wenjun YI ; Chunhong HU
Chinese Journal of General Surgery 1994;0(05):-
Objective To explore the clinico-pathological characteristics of primary breast lymphoma(PBL).Methods The clinical data of 36 cases of PBL were analyzed retrospectively.Results Among the 36 cases of PBL,16 patients presented with stage Ⅰa disease,14 patients with stage IIa disease,2 patients with stageⅡb disease,and 4 patients with stage Ⅳ.All of the patients underwent surgery and chemotherapy,and 20 cases had radiotherapy.Thirty three patients(91.7%) were followed up for 3-193 months,during which time,12 patients died,including 2 patients died of brain metastases,five patients died of bone metastasis,and five patients died of diffuse hepatic and pulmonary metastasis.In the 21 surviving patients,the survival time was 3~192 months,and the median survival time was 43.5 months.The overall 3-and 5-year survival rate was 70.1% and 49.0%,respectively.Conclusions Most PBL are NHL.PBL is diagnosed basically by methods of pathology and immunohistochemistry,and operation combined with chemotherapy and/or radiotherapy is the best treatment method.
7.Effect of dexmedetomidine on postoperative intracranial pressure in patients with severe brain injury
Xianhe ZHENG ; Shuangyan HU ; Changfeng ZHANG ; Zhonghua CHEN ; Nianping CHEN
Chinese Journal of Anesthesiology 2012;32(2):148-151
ObjectiveTo investigate the effect of dexmedetomidine on postoperative intracranial pressure (ICP) in patients with severe brain injury.MethodsNinety ASA Ⅱ or Ⅲ patients with severe brain injury,aged 19-64 yr,with Glasgow coma scale 3-7,undergoing emergency craniotomy,were randomly divided into 3 groups (n =30 each):control group (group C) and 2 different doses of dexmedetomidine groups (groups D1,D2 ).Anesthesia was induced with propofol 1.5-2.0 mg/kg,fentanyl 4 μg/kg and vecuronium 0.1 mg/kg and maintained with iv infusion of propofol and remifentanil and intermittent iv boluses of vecuronium.The patients were mechanically ventilated after tracheal intubation.Dexmedetomidine 0.3 and 0.7 μg· kg- 1· h- 1 were infused after tracheal intubation in groups D1 and D2 respectively and the infusion was maintained for 48 h.ICP was monitored after operation and maintained < 30 mm Hg by iv injection of hexadecadrol,mannitol and glycerol fructose within 2 d after operation.Venous blood samples were obtained from peripheral vein after anesthesia induction and at 6,12 and 24 h after operation (T0-3) for determination of sertum IL-1β and TNF-α concentrations by ELISA.The clinical results were evaluated using Glasgow prognosis score at 3 months after operation.The amount of hexadecadrol,mannitol and glycerol fructose consumed during 2 d after operation was recorded.ResultsCompared with T0,serum IL-1βand TNF-α concentrations were significantly higher at T1-3 in the three groups ( P < 0.05).The serum IL-1β and TNF-α concentrations at T1-3 and the amount of hexadecadrol,mannitol and glycerol fructose consumed were significantly lower,and the clinical results were significant better in groups D1 and D2 than in group C,and in group D2 than in group D1 ( P < 0.05).ConclusionDexmedetomidine can reduce postoperative ICP in patients with severe brain injury in a dose-dependent manner which is helpful for improving prognosis.The decrease in IL-1β and TNF-α levels and inhibition of inflammatory response may be involved in the mechanism.
8.The underlying mechanism of microRNA-21 in gemcitabine resistant breast cancer cells
Zhenhua WU ; Zhonghua TAO ; Jian ZHANG ; Jie XIE ; Xichun HU
China Oncology 2015;(5):326-332
Background and purpose:Gemcitabine-based chemotherapy has been shown to have signiifcant activity and favourable safety in metastatic breast cancer patients, but the effectiveness is limited due to drug resistance. MicroRNAs are a family of small non-coding RNA molecules, acting as oncogenes or tumor suppressors. Although various mechanisms of chemoresistance have been uncovered, the aberrant microRNA expression and its relationship with drug resistance of breast cancer are still unclear. This study explored the potential role and underlying mechanism of microRNA-21 in gemcitabine resistant breast cancer. Methods:MDA-MB-231 cells were continuously exposed to the increasing concentrations of gemcitabine to induce drug resistance to gemcitabine, which was 10 times more resis-tant. Then multiple methods were used including real-time PCR (RT-PCR), CCK-8, Western blot, transfection, wound healing and Transwell assay to observe the effect of microRNA-21 on epithelial-mesenchymal transition (EMT) and chemosensitivity. Results:The expression of microRNA-21 was up-regulated in gemcitabine resistant breast cancer cell line and inversely correlated with gemcitabine sensitivity. Manipulation of microRNA-21 status could change microR-NA-21 level, and could result in corresponding changes in EMT status and drug sensitivity. Conclusion:MicroRNA-21 induces gemcitabine resistance possibly via EMT process in breast cancer.
9.A retrospective study of 500 mg fulvestrant in recurrent or metastatic breast cancer patients pretreat-ed with the third generation of aromatase inhibitors
Yannan ZHAO ; Chengcheng GONG ; Xichun HU ; Zhonghua WANG ; Jian ZHANG ; Leiping WANG ; Jun CAO ; Zhonghua TAO ; Biyun WANG
China Oncology 2016;26(9):777-783
Background and purpose:The third generation of aromatase inhibitors (AI) in postmenopausal hormone receptor-positive patients is the routine treatments in endocrine therapy. The 500 mg fulvestrant showed clini-cal beneifts in patients with previous AI treatment. This study aimed to access the effcacy and safety of 500 mg fulves-trant in estrogen receptor (ER) positive postmenopausal patients who had previous AI treatments with locally advanced and metastatic breast cancer.Methods:This study retrospectively analyzed the clinical data from 188 post-AI ER positive and (or) progesterone receptor (PR)-positive locally advanced and metastatic breast cancer patients treated with 500 mg fulvestrant in Fudan University Shanghai Cancer Center from Jul. 2011 to Dec. 2015. Primary end point was progression-free survival (PFS). Secondary end points were objective response rate (ORR), clinical beneift rate (CBR) and safety proifle.Results:After the median follow-up of 11.3 months, median PFS was 5.9 months (95%CI: 4.2-7.5), CBR was 40.0% and ORR was 3.4%. COX proportional hazards regression analysis indicated that PFS was correlated with the number of metastatic sites (HR=1.92, 95% CI: 1.2-2.9,P =0.002) and previous lines of chemotherapy (HR=1.52, 95%CI:1.0-2.1,P=0.022). Six patients stopped the treatment for intolerable adverse events.Conclusion:The treatment of 500 mg fulvestrant has a favorable effcacy and safety in treatment of post-AI ER positive postmenopausal patientswith metastatic breast cancer.
10.Effects of isoflurane anesthesia on hippocampus synaptosomes proteome in aged rats
Zhonghua HU ; Rong HU ; Chengxuan QUAN ; Yi WANG ; Huijuan HE ; Guoxin LIN ; Kaiming DUAN ; Wen OUYANG
Chinese Journal of Anesthesiology 2011;31(11):1323-1326
ObjectiveTo investigate the effects of isoflurane anesthesia on hippocampus synaptosomes proteome in aged rats.MethodsTwenty-seven 22- month-old SD rats weighing 480-550 g were randomly divided into 2 groups: control group (group C,n =6) and isoflurane group (group Ⅰ,n =21 ).In group C inhaled mixed gas containing 80% oxygen for 2 h.In group Ⅰ the animals were endotracheal intubated after induction by 3% isoflurane and inhaled 2% isoflurane and 80% oxygen for 2 h.Cognition function was evaluated by Y-maze at 24 h after anesthesia and the total training times were recorded.The total training times > 75 was defined as cognitive dysfuction.In group Ⅰ the animals were divided into cognitive dysfuction group (group ⅠA) and non-cognitive dysfuction group (group IB) according to the results of Y-maze test.The animals were sacrificed and their hippocampi were removed and synaptosomes were extracted for two-dimensional gel electrophoresis.The different protein spots were analyzed by mass chromatographic analysis.ResultsSix rats had cognitive dysfuction (group IA) and another thirteen rats had no cognitive dysfuction (group IB).The total training times were significantly higher in group IA than in groups C and IB( P < 0.05).There was no significant difference in the total training times between groups C and IB (P > 0.05).There were 21 (11/10) different protein spots between groups IB and IA,and 19 (12/7) different protein spots between groups C and IA.Thirty-one protein spots were identified by means of MALDI-TOF-MS.ConclusionThe cognitive dysfuction after isoflurane anesthesia in aged rats may be related to the changes of energy metabolism protein,cytoskeletal structure and regulatory protein in synapse of hippocampus.