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Effects of astragalus polysaccharides on lipid metabolism and PPAR-α gene expression in myocardium of diabetic hamsters

Wei CHEN ; Wenjie CHEN ; Yanping XIA ; Yi LU ; Maohua YU

Fudan University Journal of Medical Sciences.2010;37(2):194-197,215.

Objective This article was designed to observe the effects of astragalus polysaccharides (APS) on glucose and lipid metabolism, and on expressions of proxisome proliferator activated receptors-α (PPAR-α) and its downstream genes in diabetic hamsters cardiomyopathy. Methods Forty-five hamsters were divided into 3 groups randomly: normal control group (15 normal hamsters), diabetic control group [15 streptozotocin (STZ)-induced diabetic hamsters], and astragalus polysaccharides (APS)-therapy group (15 STZ-induced diabetic hamsters administered with APS 2 g/kg per day orally for 10 weeks). The levels of insulin, C-peptide, myocardial enzymes, glycosylated serum protein (GSP) and lipoprotein of all hamsters were measured. The ultrastructure of myocardium was studied, and the gene and protein expressions of PPAR-α, FATP and ACS were also detected by fluorescent quantitative RT-PCR and Western blot. Results It was shown that Compared with DM group, the levels of GSP, myocardial enzymes and lipoprotein of hamsters in APS-therapy group were lower, the myocardial ultrastructure of hamsters in APS-therapy group was well-protected, and the gene and protein expression of PPAR-α, FATP and ACS of hamsters in APS-therapy group were higher. Conclusions APS is partly effective in treating diabetic cardiomyopathy.

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The role of cell apoptosis in glioma chemotherapy evaluation

Rong XU ; Yong HUA ; Ping ZHONG ; Qiwu XU ; Xiang GAO

Fudan University Journal of Medical Sciences.2009;36(6):692-695,706.

Objective To study the role of cell apoptosis during the chemotherapy of human gliocytoma in order to get effective suvilliance on the effect of chemotherapy. Methods Gliocytoma cells were isolated and cultured from 40 human gliocytoma samples. Mitochondrial membrance potential (MMP), cell cycle, the level of Bcl-2 and Bax were detected by flow cytometry (FCM) at 24, 48, 72 hours respectively of incubation with Lomustine (CCNU) and Teniposide (VM-26), and the trends were also analysed. Results MMP decreased greatly, the apoptosis part in the cell cycle ananlysis increase, the expression level of Bcl-2 decreased, and that of Bax increase rapidly, while the Bcl-2/Bax ratio decreased. Conclusions CCNU and VM-26 have singnificant effect in gliocytoma chemotherapy on inducing gliocytoma cell apoptosis. VM-26 has more stronger effect on the cell cycle. MMP is the most sensitive and the fastest index in apoptosis detection.

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The mechanism of immune antitumor effect of HS-Exo derived from heat stressed mouse hepatoma cell line (H_(22))

Di SUN ; Lin YANG ; Yi SHEN ; Shaohua WANG ; Ziwu XIANG

Fudan University Journal of Medical Sciences.2009;36(6):681-686,691.

Objective To prepare Exosomes secreted by mouse hepatoma cell (H_(22)) and heat stressed Exosomes (HS-Exo) derived from heat stress-treated mouse hepatoma cell (H_(22)), in order to study the possible anti-tumor immune mechanism. Methods Exosomes and HS-Exo were purified by serial ultracentrifugation and sucrose density gradiant centrifugation, and were observed and identified by electron microscope. The components and production of the protein and the effects of the host immune response against hepatocellular carcinoma of HS-Exo were observed by using Exosomes as the control. Their immunological factors were detected by Western blot. Lymphocyte proliferation and specific cytotoxic activity of mouse splenic cells were determined by MTT. CD4~+ and CD8~+ lymphocytes infiltration in mouse tumor tissues immunized by both were analysed by immunohistochemical staining. Results HS-Exo was similar in morphology to the Exosomes, the important immune-ralated protein expressed in HS-Exo was increased (P<0.05). HS-Exo immunized mouse group showed more effective inhibition of tumor growth, better-induced lymphocyte proliferation,more significantly enhanced the cytotoxic activity of spleen lymphocytes, as well as a more prominent role in tumor therapy than Exosomes immunized mouse control group (P<0.05). Conclusions Heat stress treatment method for the preparation of HS-Exo was feasible. HS-Exo had a stronger role in the immuneactivity and tumor treatment than control Exosomes.

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Biodistribution of iodine-131-labled chimeric monoclonal antibody in patients following intratumoral administraion in advanced lung carcinoma

Beilei LI ; Shaoliang CHEN ; Zhaoqiang XU ; Like YU ; Tian LI ; Hongcheng SHI

Fudan University Journal of Medical Sciences.2009;36(4):475-478,489.

Objective To investigate the biodistribution of intratumoral administerd~(131)Ⅰ-labeled human-mouse chimeric monoclonal antibody (chTNT) in patients with advanced lung carcinoma. Methods Eleven patients enrolled had cytological and histological confirmed diagnoses of either stage Ⅲ b or stage Ⅳ inoperable lung carcinoma. Intratumoral injection was directed by thoracic CT-guided catheter using a multi-holed needle. The dose for each patient was 18.5 - 37 MBq/cm~3 tumor mass. Blood samples were drawn at different time intervals for up to 13 days, and urine samples were collected for up to 11 days after injection for pharmacokinetic studies. In vivo stability was examined by HPLC by analyzing serum and urine, which were found to contain~(131)Ⅰ-chTNT. Whole body images were taken for quantitative organ and tumor biodistribution studies. Results In all 11 patients,~(131)Ⅰ-chTNT was the major component of the radiolabel in serum. Within 96 hours after administration, it was 100% stable. Plasma disappearance curves of ~(131)Ⅰ-chTNT were best fit by a two-exponential model in all patients with T_(1/2kα) of (0. 89±0. 17) h and T_(1/2β) of (86.88 ± 25.97)h. Free Ⅰ was the only metabolite of Ⅰ-chTNT that appeared in urine. A biodistribution study demonstrated excellent localization of the radioactivity in tumors. The accumulated radioactivity in urine at 264 h was (58.37 △Corresponding author E-mail:chen. shaoliang@zs-hospital. sh. cn±17.45) % of the injection dose. There was (51.05±8.41)%ID ,~(131)Ⅰ-chTNT in the tumor at 30 min after injection, and the tumor/lung (T/N) ratio was 63.87 ± 25.71. It remained (3.47 ± 3.27) %ID at 264 h,and the T/N ratio was 9. 61 ± 11.00. Among the main target organs, accumulation of the radiolabeled antibody was mainly found in lungs, liver, heart, kidneys, spleen and thyroid.Conclusions Pharmacokinietics of ~(131)Ⅰ-chTNT follows a two-exponential model. According to its long preservation in tumor tissue, intratumoral injection of~(131)Ⅰ-chTNT is good for tumor therapy.

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Bioavailability Evaluation of Sustained-Release Metformin Formulation After Single and Multiple Oral Dosing in Healthy Volunteers

Yanyan JIANG ; Rongqin HUANG ; Lingmei ZHENG ; Yuanying PEI

Fudan University Journal of Medical Sciences.2005;32(2):178-181.

Purpose To evaluate the relative bioavailability of a domestic sustained-release metformin tablets (SRM) compared against an immediate-release metformin tablets (IRM) using a multiple-dose,two-way crossover design after a single-dose study. Methods Eighteen healthy adult male volunteers,aged 18 to 22 years (mean,20 years),weighing 55 to 76 kg (mean,64 kg) and with height ranging from 166 to 180 cm (mean,173 cm),and blood glucose levels from 4.0 to 5.9 mmol/L (mean,4.3 mmol/L) participated in the study.The concentrations of metformin in plasma were determined using a ion-pair liquid chromatographic method. Results In single-dose study,the mean residence time (MRT),Tmax,and apparent elimination half-life (T1/2) for SRM were significantly longer and Cmax significantly lower than the corresponding values determined for IRM.The similar results were also demonstrated in multiple-dose study.The mean values of the relative bioavaibility of SRM compared with IRM in two administration ways were (85.95±0.97)% and (86.44±7.88)%,respectively.The single-dose and multiple-dose administration of the 90% confidence interval for the ratio of the logarithmic transformed AUC values of SRM over those of IRM were calculated to lie between 0.83 and 0.88,0.83 and 0.89,respectively,being within the acceptable bioequivalence limit of 0.80～1.25. Conclusion SRM was of the characteristic of sustained-release pharmacokinetics.The relative bioavailability for single dosing was similar to that of multiple dosing,and both of the administration ways demonstrated bioequivalence in absorption between SRM and IRM.

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Clinical Effects of Severe Alkali-burned Eyes with Early Lamellar Corneoscleral Transplantation

Yutao ZOU ; Xiaozhi QIU ; Qiyi HU

Fudan University Journal of Medical Sciences.2000;27(6):477-479，487.

Purpose　To evaluate the clinical effects of early lamellar corneoscleral transplantation in the management of severe alkali-burned eye.　Methods　The patients compatible with the Ⅲ or Ⅳ grades of Roper-Hall's standards were diveded into operating group and control group according to the post-burning interval which was less than 2 weeks or more.Depending on the presence or absence of scleral nacrosis,the patients in operating group were given a lamellar corneoscleral transplantation or a lamellar keratoplasty.The patients in control group did not receive any operation.The medication was the same in the two groups.　Results　During the following-up of 6 to 24 months,most cases in operating group had significantly improved vision postoperatively,less inflammatory congestion,lower incidence of corneal ulcertion,and less neovasculerization.No perforation occurred in any case of the operating group.Whilst in the control group,ulcerative perforation occurred in 6 of 10 eyes,leucoma accompanied by severe panus in 6 eyes,symblepharon in 5 eyes.　Conclusions　Debridement with early lamellar corneoscleral transplantation can effectively decrease the occurrence of corneal perforation,prevent symblepharon,shorten the time of inflammation,and improve visual acuity.

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Experimental Study on Treatment of Bronchial Asthma With Antisense Oligonucleotid

Meiqin WANG ; Chunxue BAI ; Shanfu NIU ; Xiaohui FANG ; Changqing CHEN ; Bo CHEN

Fudan University Journal of Medical Sciences.2000;27(6):464-467，470.

Purpose　To explore the possibility and the effect of therapeutic bronchial asthma by antisense oligonucleotid.　Methods　Based on the IL-5 cDNA sequence of mouse,a segment of antisense oligonucleotid was designed and synthetized.5′-labeling of antisense oligonucleotid was signed by T4 PNK in order that the efficiency of stearylamine liposome in transfe-ting antisense oligonucleotid can be evaluated. Astham model was duplicated with ovalbumin (OVA) absorbed to aluminum hydroxide. T lymphocytes of mice were separated by nylon fiber method,then T lymphocytes transfected a different content of antisense oligonucleotid with stearylamine phys. positive liposome were cultured respectively in order to observe the effect of antisense oligonucleotid on IL-5 produced by T lymphocytes. IL-5 levels in the supernatants of T lymphocytes culture were determined by ELISA.　Results 　Stearylamine liposome could markedly increase the efficiency of antisense oligonucleotid transfection. The efficiency of antisense oligonucleotid transfection was the best at 1∶15 m/m(antisense oligonucleotid and SA liposome) and it was increased approximately 12 times.In healthy and asthma Balb/c mice, IL-5 was not detected in the supernatants of T lymphocytes culture without challenge with OVA.However,IL-5 was increased markedly in the supernatants of T lymphocytes culture challenged with OVA. After transfecting a different concentration antisense oligonucleotid, IL-5 levels in the supernatants of T lymphocytes culture were significantly lower than those in control cells without antisense oligonucleotid transfection. IL-5 levels decreased from (44.60±6.23) to (30.70±7.362),(17.20±6.181) and(8.16±2.34)pg/ml respectively. And IL-5 synthesis was inhibited by 31.17% , 61.43% and 81.7% respectively. 　Conclutions　IL-5 synthesis could be obviously inhibited by antisense oligonucleotid and showed a markedly relation between quantitative and effect. It is supported that the production of IL-5 be inhibited through preventing the transcription of IL-5 from T lymphocytes. The study provides foundation for antisense gene therapeutic asthma.

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Exogenous EGF Effect on Change of Ultra-structure in Sensory Neuron Following Nerve Injury in Rat

Feng ZHANG ; Yudong GU ; Jianguang XU ; Jifeng LI

Fudan University Journal of Medical Sciences.2000;27(6):446-448，452.

Purpose　To observe exogenous epidermal growth factor (EGF) influence upon sensory neurons axotomy-induced and change ultra-structure of sensory.　Methods　Eighteen male Sprague-Dawely rats weighing 180-200 g(8-9 weeks of age)were randomly divided into two groups.One as control,the other was treated with EGF.Sciatic nerve injury model was set up by transecting left side sciatic nerve at 0.5 cm away from performed muscle.The proximal stump of sciatic nerve was ligated to inhibit nerve regeneration.Then 5 μl of normal saline in the control groups and an equal volume of EGF solution (containing 10 μg EGF) in the EGF treated groups were injected into the proximal of ligated nerve.The rats were sacrificed in 7,14,28 days of operative intervals respectively and transcardialy perfused with 4% para-fromaladehyde.The L5 dorsal root ganglion(DRG) were harvested.Eletromicroscope technique was used to observe the changes of L5 DRG sensory neurons axotomy-induced.　Results　A series of changes happened in the control group.The size of the nucles decreased.Nucleoplasm was scattered.The nucleolus was pale.Edema,loss of crest and matrix was found in the mitochondria. Satellite cells detached from the soma.The ultrastructure of L5 DRG sensory neurons in EGF groups get near to normal following nerve injury.　Conclusions　EGF could protect sensory neurons.

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Safety and effectiveness of domestic bovine pericardium as ovine pulmonary artery and descending aorta patch

Abudupataer MIERADILIJIANG ; Shuyang LU ; Jinmiao CHEN ; Chen HE ; Chunsheng WANG ; Tao HONG

Fudan University Journal of Medical Sciences.2017;44(2):206-212. doi:10.3969/j.issn.1672-8467.2017.02.014

Objective To evaluate the safety and effectiveness of a newly domestic bovine pericardium using a juvenile sheep model and to provide proof for clinical use.Methods Under the off-pump condition,8 domestic bovine pericardiums were implanted into the pulmonary artery and the descending aorta of 4 juvenile sheep as the trial group.As the control group,four imported bovine pericardiums were implanted into two juvenile sheep.Before the surgery,the juvenile sheep were given a physical examination and some laboratory tests.Ultrasonic cardiographs were taken after 1 month and 2 months of implantation.Sheep were sacrificed after 90 days and compared with the extent of endothelialization,inflammation and calcification of the two groups.Results (1) All the juvenile sheep survived without any complications.(2) Ultrasonic cardiograph showed the absence of leakage,thrombus,calcification,neoplasm or any structural deterioration.(3) Gross examination showed there was no intimal hyperplasia.The thickness and tenacity of all patches had no change compared with the pre-operation condition.All the patches showed smooth and pliable faces without degeneration,as well as absence of macroscopically calcification.(4) There was not any positive result in microbiological tests in both groups.The degree of inflammation,necrosis and calcification had no significant differencs between the two groups.Conclusions The data shows that the domestic bovine pericardium,a newly developed Chinese domestic-design and manufactured bovine pericardium,can exhibit long-term satisfactory safety and efficacy in the implantation of the pulmonary artery and the descending aorta of juvenile sheep.

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Analysis of preoperative risk factors of postoperative complications in patients undergoing endovascular repair surgery

Junke LI ; Shengjin GE ; Wei CHEN

Fudan University Journal of Medical Sciences.2017;44(2):202-205. doi:10.3969/j.issn.1672-8467.2017.02.013

Objective To summarize the perioperative outcomes of patients undergoing endovascular repair,and to screen out related preoperative risk factors in order to provide reference for the promotion of postoperative rehabilitation of patients.Methods The clinical data of 2 896 patients undergoing elective endovascular repair in the Department of Vascular Surgery,Zhongshan Hospital,Fudan University from Jan.2013 to Dec.2014 were analyzed to screen out related preoperative risk factors of postoperative complications retrospectively.Results A total of 148 patients had postoperative complications,including 2 cases of death during hospitalization.The incidence of complications in the patients older than 75 years old,with hypertension,diabetic mellitus,renal dysfunction,chronic obstructive pulmonary disease (COPD) or ASA physical status more than grade Ⅱ is 9.7％,8.1 ％,14.3 ％,8.0 ％,29.7 ％,6.3 ％,respectively.The multivariate Logistic regression analysis identified that patients older than 75 years old (P =0.000,OR =43.29,95％CI:22.51-83.28),with hypertension (P=0.000,OR=3.822,95 ％CI:2.37-6.16),diabetic mellitus (P=0.025,OR=1.714,95％CI:1.07 -2.75),renal dysfunction (P =0.017,OR =2.692,95 ％ CI:1.19-6.07) or COPD (P =0.000,OR =7.158,95％CI:3.83-13.37) and ASA physical status more than grade Ⅱ (P =0.000,OR =27.77,95％CI:13.79-55.93) were the independent risk factors with postoperative complications of endovascular repair surgery.Conclusions The patients older than 75 years old,with hypertension,diabetic mellitus,renal dysfunction or COPD and ASA physical status more than grade Ⅱ were the independent risk factors for endovascular repair surgery.

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