1.Effects of bone marrow mononuclear cell implantation induced by 5-azacytidine on cardiac function
Hongxin XU ; Gengshan LI ; Hong JIANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2003;0(02):-
Objective: Recent studies have shown that cell implantation can replace infarcted myocardium to improve cardiac performance. The present study was designed to investigate the effects of autologous bone marrow mononuclear cell (BM-MNC) implantation into myocardium bordering the infarction with or without induced by 5-azacytidine on cardiac function after acute myocardial infarction (AMI) in rabbits. Methods: AMI was replicated by ligating the left anterior descending coronary artery. Rabbits were randomly divided into three groups: (1) BM -MNC induced by 5-azacytidine implantation (n=7), (2) BM-MNC implantation alo ne (n=7), and (3) AMI control (n=7). In addition, sham-operated (n=5) rabbit s were randomly selected to serve as non-infarction control. Animals for cell im p lantation were received intramyocardial injection of autologous BM-MNC in myoca rdium bordering the infarction, and echocardiography and hemodynamic studies wer e performed to evaluate cardiac function following 28 days of implantation. Results: Compared with the sham-operated group, the left ventricle (LV) end diastolic pressure (LVEDP) was significantly increased (P0.05). Conclusion: BM-MNC induced by 5-azacytidine implantation into myocardium bordering the infarction can significantly improve impaired cardiac function associated with LV remodeling after AMI, however such improvement is not further promoted compared with that in BM-MNC implantation group alone.
2.Protective effects of trimetazidine on bone marrow mesenchymal stem cells viability in an ex vivo model of hypoxia and in vivo model of locally myocardial ischemia.
Hongxin, XU ; Gangyan, ZHU ; Yihao, TIAN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(1):36-41
Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. The present study was to investigate whether trimetazidine (TMZ) could improve survival of MSCs in an ex vitro model of hypoxia, as well as survival, differentiation, and subsequent activities of transplanted MSCs in rat hearts with acute myocardial infarction (AMI). MSCs at passage 3 were examined for their viability and apoptosis under a transmission electron microscope, and by using flow cytometry following culture in serum-free medium and exposure to hypoxia (5% CO(2), 95% N(2)) for 12 h with or without TMZ. Thirty Wistar rats were divided into 3 groups (n=10 each group), including group I (AMI control), group II (MSCs transplantation alone), and group III (TMZ+MSCs). Rat MSCs (4×10(7)) were injected into peri-infarct myocardium (MSCs group and TMZ+MSCs group) 30 min after coronary artery ligation. The rats in TMZ+MSCs group were additionally fed on TMZ (2.08 mg·kg(-1)·day(-1)) from day 3 before AMI to day 28 after AMI. Cardiac structure and function were assessed by echocardiography at 28th day after transplantation. Blood samples were collected before the start of TMZ therapy (baseline), and 24 and 48 h after AMI, and inflammatory cytokines (CRP, TNF-α) were measured. Then the survival and differentiation of transplanted cells in vivo were detected by immunofluorescent staining. The cellular apoptosis in the peri-infarct region was detected by using TUNEL assay. Furthermore, apoptosis-related proteins (Bcl-2, Bax) within the post-infarcted myocardium were detected by using Western blotting. In hypoxic culture, the TMZ-treated MSCs displayed a two-fold decrease in apoptosis under serum-free medium and hypoxia environment. In vivo, cardiac infarct size was significantly reduced, and cardiac function significantly improved in MSCs and TMZ+MSCs groups as compared with those in the AMI control group. Combined treatment of TMZ with MSCs implantation demonstrated further decreased MSCs apoptosis, further increased MSCs viability, further decreased infarct size, and further improved cardiac function as compared with MSCs alone. The baseline levels of inflammatory cytokines (CRP, TNF-α) had no significant difference among the groups. In contrast, all parameters at 24 h were lower in TMZ+MSCs group than those in MSCs group. Furthermore, Western blotting indicated that the expression of anti-apoptotic protein Bcl-2 was up-regulated, while the pro-apoptotic protein Bax was down-regulated in the TMZ+MSCs group, compared with that in the MSCs group. It is suggested that implantation of MSCs combined with TMZ treatment is superior to MSCs monotherapy for MSCs viability and cardiac function recovery.
3.Vascular imaging research of patients with cervical vertigo
Hongxin ZHANG ; Jun LIU ; Liang XU ; Caixian HAO
Journal of Practical Radiology 2016;32(3):419-422
Objective To analyze the imaging characteristics and to evaluate the application value of color doppler ultrasonography (CDUS)combined with CT angiography (CTA)and contrast-enhanced magnetic resonance angiography (CE-MRA)in patients with cervical vertigo.Methods 62 patients diagnosed with cervical vertigo clinically were enrolled.Neck CDUS and neck CTA were per-formed on 39 patients.Neck CDUS and neck CE-MRA were performed on 23 patients.Neck CDUS and CTA/MRA were performed on 30 normal volunteers,which were chosen as control group.Neck CDUS and neck CTA were performed on 18 normal volunteers. Neck CDUS and neck CE-MRA were performed on 12 normal volunteers.Hemodynamics and morphology were evaluated and com-pared between the two groups.Results In aspect of morphology:The incidence of vertebral artery (VA)stenosis (46.77%)and VA variation (29.03%)in cervical vertigo group were higher than VA stenosis (23.33%)and VA variation (6.67%)in control group with significant difference (all P <0.05).The incidence of tortuous VA showed no statistics difference between cervical vertigo group (1 1.29%)and control group (13.33%)(P >0.05).In aspect of hemodynamics:The decline incidence of peak systolic velocity de-tected by CDUS in cervical vertigo group (66.13%)was higher than that in control group (10.00%)with statistically significant difference (P <0.05).The peak systolic velocity decline incidence of VA stenosis (86.21% )and VA variation (72.22%)were high-er than that of VA tortuous (28.57%)and VA normal (12.50%)patients in cervical vertigo group.Conclusion The application of CDUS combined with CTA or CE-MRA could provide valuable diagnostic and therapeutic information for cervical vertigo in the as-pects of change in vascular morphology and cerebral hemodynamics,which could further provide objective basis for clinical diagnosis and treatment.
4.The follow-up study of image guided 125I seed permanent brachytherapy for the treatment of unresectable pancreatic cancer
Hongxin NIU ; Xikun ZHANG ; Zhongfa XU ; Zhao ZHOU
Chinese Journal of General Surgery 2015;30(6):432-435
Objective To explore the clinical efficacy of image-guided 125I radioactive seed interstitial implantation therapy for unresectable pancreatic cancer.Methods 25 patients with unresectable pancreatic cancer evaluated by retrospective follow-up were enrolled in this study,13 patients received radioactive seeds implantation while 12 patients were given non-surgical treatment.We observe and compare the clinical benefits,objective curative effect,complications,adverse reaction,survival between the two groups of patients.Results Compared with the non-surgical treatment group,the clinical benefit rate in the radiotherapy seed implantation group was 92% (12/13) while that of the non-surgical group was 42% (5/12),the difference was of statistically significance.The numbers of cases evaluated as effective were 6 (46%) and 4 (33 %) respectively,the difference was not statistical significant (x2 =0.427,P > 0.05);The radioactive seed implantation group had no serious postoperative complications;3 cases who received subsequent chemotherapy in radioactive seed implantation group(23%,3/13) and 3 cases in non-surgical treatment group(25%,3/12)suffered from serious adverse reactions,the difference was of no statistical significance(x2 =0.013,P >0.05);Comparing the survival rate between the two groups,x2 =0.001,P =0.969,the difference was of no statistical significance.Conclusions The therapy of 125I radioactive seed implantation for unresectable pancreatic cancer significantly relieves cancer caused pain and improves quality of life.
5.Analysis of clinical and pathological features of familial gastric cancer
Hongxin NIU ; Zhongfa XU ; Huiyong SHI ; Lili WANG
Chinese Journal of Current Advances in General Surgery 2009;0(11):-
Objective:To explore the clinical and pathological features of familial gastric cancer, and to get the early discovery and early treatment of it.Methods:Two kindreds of familial gastric cancer were followed up and their clinical and pathological features were analyzed.Results:Six patients with gastric cancer were found in the 2 kindreds.Autosomal dominant inheritance was observed in these cases.clinical and pathological features of familial gastric cancer were showed according to the document analysis:early onset;poor prognosis;patients suffer simultaneous or metachronous carcinoma;CDH1 germline mutation carriers had higher penetrance;pathologically, tumors are mostly diffuse infiltrative type with lower differentiated degree and earlier metastasis to lymphnodes;in one kindred,the sites of the lesions were relatively consistent.Conclusion:Familial gastric cancer has particular clinical and pathological features:early onset;poor prognosis;patients suffer simultaneous or metachronous carcinoma;CDH1 germline mutation carriers have higher penetrance; pathologically,tumors are mostly diffuse infiltrative type with lower differentiated degree and earlier metastasis to lymphnodes.
6.Study on Nuclear Factor-?B Activation in Skin Lesions of Systemic Lupus Eryt hematosus
Chunhong FANG ; Hong LIANG ; Jianjun LI ; Hongxin XU ; Layuan XIONG
Chinese Journal of Dermatology 1994;0(06):-
Objective To examine whether activation of nuclear factor-?B (NF-?B) exists in skin lesions of patients with systemic lupus erythematosus (SLE ) and its association with disease activity. Methods The skin lesions were inves tigated histopathologically in patients with SLE, and NF-?B activation was ass essed by immunohistochemical analysis semi quantitatively. Results Expression o f NF-?B was found on skin lesions in 14 of 15 patients with SLE, including 8 s trong positive (), 3 moderate positive (), and 3 mild positive (+). Brown-coloured particles were mainly distributed in keratinocytes, especially in prick le cells and granular layer cells, as well as in mononuclear cells of dermis. Th ere was no correlation between NF-?B activation and disease activity. However, NF-?B was not detected in skin lesions of all patients with non-SLE and heal thy controls. Conclusions NF-?B activation may be associated with the developm ent of skin lesions in patients with SLE,and not with disease activity.
7.Sedative and hypnotic interaction between propofol and remifentanil by target-controlled infusion during induction of anesthesia
Hongxin JI ; Xingan ZHANG ; Qunlin WU ; Weidong SHAO ; Bo XU ; Chong SHI ; Jie WANG
Chinese Journal of Anesthesiology 2010;30(3):269-272
Objective To investigate the sedative and hypnotic interaction between remifentanil and propofol by target-controlled infusion (TCI) during induction of anesthesia.Methods Third-two ASA Ⅰ or Ⅱpatients,aged 22-63 yr,body mass index 18-25 kg/m2,scheduled for elective surgery under general anesthesia,were randomly divided into 4 groups(n=8 each).Group Ⅰ only received TCI pmpofol.GroupⅡ,Ⅲ,and Ⅳreceived a target concentration of 2,4 or 6 ng/ml remifentanil respectively.While the blood-effect site concentrations of remifentanil were equilibrated,patients received TCI of propefol,with an initial target concentration of 0.5μg/ml.After the blood-effect site concentrations of propofol were equilibrated then with 0.5μg/ml increments until the loss consciousness was achieved.The eyelash reflex and state of consciousness were assessed and radial arterial blood sample 6 ml was taken every 3 min to determine the remifentanil and propofol concentrations in blood.Propofol and remifentanil concentrations in blood were measured by reversed-phase high-performance liquid chromatography and high-performance liquid chromatography with ultraviolet detection respectively.The sedative and hypnotic interaction between propofol and remifentanil was determined with a pharmacodynamie interaction model by regression analysis and determined using the isobolographic method.Results Propofol concentrations in blood were lower in group Ⅱ,Ⅲ and Ⅳ than group Ⅰ(P<0.05).The propofol concentratopms in blood were significantly decreased in trun with the increase in the remifentanil concentrations in blood in group Ⅱ-Ⅳ(P<0.05).At loss of eyelash reflex and loss of consciousness of patients,the pharmacodynamic interaction model by curve fitting was superior to linear regression (P<0.05).At loss of eyelash reflex of patients,the curve fitting result showed EC50,prop=2.77μg/ml and EC50,rem=26.67 ng/ml,and the isobolographic method equation is ECprop/2.77+ECrem/26.67=0.69.At loss of consciousness of patients,the curve fitting result showed EC50,prop==3.76μg/ml and EC50,rem=31.56ng/ml,and the isobolographic method equation is Ecprop/3.76+Ecrem/31.56=0.65.Conclusion Remifentanil (Cp 2-6 ng/ml) and propofol by TCI shows a synergistic type of pharmacodynamic interaction on the sedative and hypnotic during induction of anesthesia.
8.Effect of valsartan on atherosclerosis in the cholesterol-fed rabbits
Hongxin XU ; Jianjun LI ; Gengshan LI ; Jing WANG ; Xiaoyan LI ; Xuejun JIANG
Chinese Journal of Pathophysiology 1986;0(04):-
AIM: To investigate whether valsartan inhibits the development of atherosclerosis in cholesterol-fed rabbits and its possible mechanism. METHODS: Male rabbits were fed either: (1) normal rabbit chow for 16 weeks; (2) 1.5% cholesterol diet for 16 weeks; or (3) 1.5%cholesterol diet for 16 weeks supplemented by valsartan(3 mg?kg -1?d -1) for the last 4 weeks. After 16 weeks, the arteries were harvested for histomorphometry and immunohistochemistry. RESULTS: Rabbits fed with cholesterol-rich diet showed higher serum lipids levels(P
9.The cardiac functional affection by trimetazidine administration plus bone marrow stem cells transplanting in rats after myocardial infarction
Hongxin XU ; Yihao TIAN ; Hong JIANG ; Xuejun JIANG ; Qing ZHOU ; Ruiqiang GUO
Chinese Journal of Ultrasonography 2009;18(11):973-976
Objective To observe the rat cardiac size and cardiac function changes before and after trimetazidine administration plus bone-marrow stem cells transplanting through echocardiography.Methods Forty wistar rats were divided into the following 4 groups randomly:control group (T),myocardial infarction group (Ⅱ),bone marrow stem calls transplantation group (Ⅲ),and bone marrow stem cells transplantation plus trimetazidine administration group(Ⅳ).The rats' left anterior coronary artery in group Ⅱ,Ⅲ and Ⅳwas ligated to produce myocardial infarction model,then bone-marrow stem cells were injected around the infarcted area into the later two groups.Furthermore,rats in group Ⅳ were administrated with trimetazidine.The size and systolic function of the hearts were measured 4 weeks after transplantation.The left ventricular systolic pressure(LVSP) and the end-diastolic pressure(LVEDP) were also measured at the end of experiment.Results The left ventricular diameter of rats in group Ⅲ and Ⅳ was smaller than that in group Ⅱ,and the ventricular systolic function increased,LVSP increased and LVEDP decreased statistically in group Ⅲ and Ⅳ.the amelioration of cardiac size and function was significantly notable in group Ⅳ than that in group Ⅲ.Conclusions Bone marrow stem cells transplantation can release the enlargement of left ventricle and improve cardiac function after myocardial infarction.The therapeutic efficacy can be further elevated if administrated with trimetazidine simultaneously.
10.Preparation and evaluation of doxorubicin hydrochloride liposomes modified by poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate.
Di ZHANG ; Jianying LI ; Xiaochan WANG ; Hongxin YUE ; Meina HU ; Xiu YU ; Huan XU
Acta Pharmaceutica Sinica 2015;50(9):1174-9
In this study, the buffering capacity of amphiphilic pH-sensitivity copolymer poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (PEOZ-CHMC) was evaluated. The ammonium sulfate gradient method was used to prepare doxorubicin hydrochloride (DOX x HCl)-loaded liposomes (DOX-L), and then the post-insertion method was used to prepare PEOZ-CHMC and polyethylene glycol-distearoyl phosphatidyl ethanolamine (PEG-DSPE) modified DOX x HCl-loaded liposomes (PEOZ-DOX-L and PEG-DOX-L). The physico-chemical properties, in vitro drugs release behavior, cellular toxicity and intracellular delivery of liposomes were evaluated, separately. The results showed that PEOZ-CHMC has a satisfactory buffering capacity. The sephadex G-50 column centrifugation method and dynamic light scattering were used to determine the encapsulation efficiency (EE) and particle size of liposomes. The EE and particle size of DOX-L were (97.3 ± 1.4) % and 120 nm, respectively, and the addition of PEOZ-CHMC or PEG-DSPE had no influence on EE and particle size. The zeta potentials of three kinds of liposomes were negative. The release behavior of various DOX liposomes in vitro was investigated by dialysis method. In phosphate buffer solution (PBS) at pH 7.4, DOX x HCl was released from PEOZ-DOX-L in a sustained manner. While in PBS at pH 5.0, the release rate of DOX x HCl from PEOZ-DOX-L increased significantly, which suggested DOX x HCl was released from PEOZ-DOX-L in a pH-dependent manner. The intracellular delivery of liposomes was investigated by confocal laser scanning microscopy (CLSM). The CLSM images indicated that PEOZ-DOX-L showed efficient intracellular trafficking including endosomal escape and release DOX x HCl into nucleus, as well as the DOX-L and PEG-DOX-L had no this effect. The cytotoxicity of liposomes against MCF-7 cells was detected by using MTT assay. The results showed that antiproliferative effects of PEOZ-DOX-L enhanced with pH value decreased, whereas DOX-L and PEG-DOX-L did not have any significant difference in inhibitions at different pH conditions. Therefore, the problems of the inhibition of cellular uptake of liposomes and the failed endosomal escape of pH-sensitive liposomes by PEG chain can be overcome by the pH-sensitive liposomes constructed by PEOZ-CHMC.