1.Comparative study on the clinical outcome following different doses of amphotericin B liposome in the treatment of patients with invasive pulmonary fungal infections after renal transplantation
Ding LIU ; Yongguang LIU ; Xianghua SHI ; Ming ZHAO ; Ying GUO
Chinese Journal of Organ Transplantation 2012;33(8):481-484
ObjectiveTo compare the clinical effectiveness and adverse effects following low doses versus traditional doses of amphotericin B liposome (L-AmB) in the treatment of patients with invasive pulmonary fungal infections (IPFI) after renal transplantation.MethodsA total of 26 postrenal transplantation patients with IPFI between Jan. 2005 and Mar. 2011in Zhujiang hospital received L-AmB treatment identified low doses group (0.2-0.5 mg·kg-1·d-1,n =19) or traditional doses group (1-5 mg· kg-1,d-1,n =7) were reviewed.ResultsThe treatment duration in low doses group and traditional doses group was 20.3 +12.7 and19.3 ±13.2 days respectively (P>0.05).The effective rate in low doses group and traditional doses group was 84.2% and 57.1% respectively (P>0.05).The overall dosage was significantly less in the low doses group (414.7 ± 241.7 mg) than in the traditional doses group (1158.8 ± 928.0 mg) (P<0.05).The incidence of adverse effect was significantly lower in the low doses group than in the traditional doses group (21.1% vs.85.7%,P<0.05).ConclusionThe effectiveness of low doses of L-AmB protocol in the treatment of IPFI postrenal transplantation patients was similar to that of traditional doses of L-AmB protocol,but the incidence of adverse effects in low doses of L-AmB protocol was significantly lower.
2.Inhibiting NF-κB activity down-regulates angiotensinogen expression level in cultured rat mesangial cells
Jin LI ; Ying GUO ; Bin HUANG ; Helin DING ; Zuzhi FU
Chinese Journal of Endocrinology and Metabolism 2010;26(5):411-412
The angiotensinogen(AGT) expression and angiotensin Ⅱ (AngⅡ ) secretion levels in cultured SD rat mesangial cells were determined. High glucose up-regulated AGT mRNA(0. 29±0.07 vs 0. 20±0. 05,P< 0.05)and protein(0.66±0.23 vs 0.37±0. 15,P<0.05) expression and Ang Ⅱ secretion [(9.85±2.08 vs 7.50± 1. 51) pg/ml,P<0. 05]levels, which were down-regulated by pyrrolidine dithiocarbamate( PDTC) treatment via inhibiting NF-κB activity.
3.Characterization of the primary structure of TNK-tissue plasminogen activator using LC-MS.
Lei TAO ; Youxue DING ; Ying GUO ; Chunming RAO ; Junzhi WANG
Acta Pharmaceutica Sinica 2013;48(6):896-900
The primary structure of TNK-tissue plasminogen activator (TNK-tPA) was characterized using liquid chromatography-mass spectrometry (LC-MS). Firstly, the molecular mass of deglycosylated protein was measured. Then peptide mass mapping and MS/MS of the reduced, alkylated and trypsin-digested sample were tested and analyzed so as to verify its amino acid sequence and identify post-translational modifications. Results show that the amino acid sequence was consistent with designed structure; about 5% of M207 was oxidized; T61 was fucosylated with -80% occupancy; N103, N448 and N184 (-15% occupancy) were glycosylated with complex-type oligosaccharides. LC-MS coupled with proper sample pretreatment is approved to be a rapid and powerful approach to characterize the primary structure of TNK-tPA.
4.C936T polymorphism in 3'-untranslated region of vascular endothelial growth factor gene is associated with diabetic nephropathy in type 2 diabetics
Xinhuan ZHANG ; Ying GUO ; Lihong CHEN ; Helin DING ; Zuzhi FU
Chinese Journal of Endocrinology and Metabolism 2008;24(3):299-301
The relationship between C936T polymorphism at 3'-untranslated region of vascular endothelial growth factor (VEGF) gene and diabetic nephropathy (DN) was analysed in 194 type 2 diabetic patients. The frequencies of genotype CC and allele C were significantly higher in DN group than those in non-DN group and control group. Allele C and genotype CC of VEGF may be a genetic marker susceptible to DN.
5.Clinical efficacy and safety of conversion from cyclosporine A to tacrolimus-based regimen for different pathological types of chronic allograft nephropathy patients
Sen GAO ; Yi GAO ; Yongguang LIU ; Ding LIU ; Ying GUO
Chinese Journal of Tissue Engineering Research 2010;14(18):3408-3411
BACKGROUND: Recent studies have suggested that conversion from cyclosporine A (CsA) to tacrolimus (FK 506)-based regimen can improve renal allograft function and survival rate. But little is known about whether the conversion from CsA to tacrolimus(FK 506) plus mycophenolate mofetil (MMF)-based regimen exhibits the same or similar clinical efficacy. OBJECTIVE: To investigate the clinical efficacy and safety of converting CsA to FK506 plus MMF in treatment of different types of chronic allograft nephropathy (CAN). DESIGN, TIME AND SETTING: An observational and controlled trial was performed at the Center for Organ Transplantation, Zhujiang Hospital, Southern Medical University from January 2005 to October 2007. PARTICIPANTS: Fifteen-nine enrolled patients received CsA-based regimen after renal allografting. Following pathological confirm and typing, all patients were assigned to two groups: CAN with chronic rejection (CR, n = 31) and CAN without chronic rejection (non-CR, n = 28). FK 56 was purchased from Fujisawa Pharmaceutical Company, Ltd., Japan. MMF was sourced from Shanghai Roche Pharmaceutical Co., Ltd., China. METHODS: When patients were diagnosed CAN, the CsA regimen was conversed to FK506 plus MMF regimen. FK506 initiated at a dose of 0.08 mg/kg per day and then was adjusted to achieve steady-state whole blood trough levels of approximately 5-8 μg/L. MMF was used at a fixed dosage, 1.0 g/d, twice a day, only if relative adverse events occurred. All patients were followed up at least 6 months. MAIN OUTCOME MEASURES: Serum creatinine(Scr), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), 24-h proteinuria, glomerular filtration rate (GFR), and complications. RESULTS: All initial 59 patients were included in the final analysis. At 6 months after regimen conversion, the levels of Scr, TC, TG, LDL, and 24-hour proteinuria were significantly reduced in non-CR, in particular CR, groups, compared with prior to conversion (P< 0.05). GFR was markedly increased in both the CR and non-CR groups (P< 0.05). In the CR group, 20 patients obtained improved results, 7 got stable results, and 4 showed ineffective results. The effective rate of regimen conversion was 64.5% and 32.1% in the CR and non-CR groups, respectively, and significant difference existed between the two groups (P < 0.05). Compared with prior to conversion, the incidence of hypertension and hyperlipemia was significantly decreased after regimen conversion (P< 0.05). There was no significant difference in diabetes mellitus, opportunistic infection, and malignancy between prior to and after regimen conversion. CONCLUSION: FK506 plus MMF-based regimen can markedly improve the function of renal graft of CAN, in particular CR, patients.
6.The development of interdisciplines for contemporary medicine
Zhide DING ; Wei GUO ; Tingxiang ZHANG ; Ying QIN ; Jiayu YAN ; Xiaoying XI
Chinese Journal of Medical Science Research Management 2010;23(5):289-291
We have investigated the situation about recent interdisciplinary construction for medical subject from several 985-project universities in China as well as the well-known overseas universities via internet. We also have analyzed the results and in mean time, put forward some related suggestions in order to probe an available strategy of interdisciplinary construction for medical subject in the universities of China.
7.Effects of parathyroid hormone on synthesis and degradation of extracellular matrix in cultured human renal tubular epithelial cells
Xiaodong LI ; Ying LI ; Xinguo DING ; Hongmei ZHANG ; Shanlin GAO ; Zhijun GUO
Chinese Journal of Nephrology 2010;26(6):448-452
Objective To investigate the effects of parathyroid hormone (PTH) on the synthesis and secretion of collagen Ⅲ and fibronectin (FN), and the expressions of plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA in cultured human renal tubular epithelial cells (HK-2).Methods HK-2 cells were cultured in DMEM-F12 medium supplemented with 5% FBS. Cells were exposed to different concentrations of PTH (0, 10-12, 10-11, 10-10, 10-9, 10-8 mol/L) for 48 h, or 10-8 mol/L PTH at different time (0, 12, 24, 48, 72 h). The gene expressions of collagen Ⅲ,FN, PAI-1, MMP-1, and TIMP-1 were detected by semi-quantitative RT-PCR. The protein expression of collagen Ⅲ was detected by Western blotting. The level of FN in the supernatant was assayed by enzyme linked immunosorbent assay (ELISA). Results PTH increased gene expressions of collagen Ⅲ, FN, PAI-1 and TIMP-1 in a dose- and time-dependent manner, but decreased MMP-1 gene expression. Then the ratio of MMP-1/TIMP-1 was decreased. PTH increased the collagen Ⅲ protein expression in cultured HK-2 cells and the level of FN in the supernatant of cultured HK-2 cells in a dose- and time-dependent manner. Conclusion PTH can up-regulate PAI-1, TIMP-1 gene expressions, and down-regulate MMP-1 gene expression,resulting in elevation of extracellular matrix (ECM) synthesis and reductim of degradation.
8.Quality control of recombinant oncolytic adenovirus/p53.
Kai GAO ; Hua BI ; Youxue DING ; Yonghong LI ; Chunmei HAN ; Ying GUO ; Chunming RAO
Acta Pharmaceutica Sinica 2011;46(12):1476-82
To establish a detection method of oncolytic adenovirus/p53 and standard of quality control, human telomerase reverse transcriptase (hTERT) promoter, CMV fusion promoter containing hypoxia reaction element (HRE) and p53 gene were identified by vector DNA restriction enzyme digestion and PCR analysis. The result conformed that all modified regions were in consistent with theoretical ones. Particle number was 2.0 x 10(11) mL(-1) determined by UV (A260). Infectious titer was 5.0 x 10(10) IU mL(-1) analyzed by TCID50. In vitro p53 gene expression in human lung cancer cell H1299 was determined by ELISA, and A450 ratio of nucleoprotein in virus infection group to control group was 5.2. Antitumor potency was evaluated by cytotoxicity assay using human lung cancer cell A549, and the MOI(IC50) of this gene therapy preparation was 1.0. The tumor cells targeted replication ability of recombinant virus was determined by TCID50 titer ratio of filial generation virus between human lung cancer cell A549 and human diploid epidermal fibrolast BJ cells after infected by virus with same MOI. TCID50 titer ratio of tumor cell infection group to normal cell infection control group was 398. The IE-HPLC purity of virus was 99.5%. There was less than 1 copy of wild type adenovirus within 1 x 10(7) VP recombinant virus. Other quality control items were complied with corresponding requirements in the guidance for human somatic cell therapy and gene therapy and Chinese pharmacopeia volume III. The detection method of oncolytic adenovirus/p53 was successfully established for quality control standard. The study also provided reference for quality control of other oncolytic viral vector products.
9.Sampling Results and Quality Assessment of Recombinant Human Interferon α2 a Injections
Dening PEI ; Ying GUO ; Yonghong LI ; Chunmei HAN ; Youxue DING ; Xiang LI
China Pharmacist 2015;(1):52-54,55
Objective: To evaluate the quality status of recombinant human interferon α2a injections and find out some quality problems. Methods:The statutory testing methods combining with the exploratory studies were used to examine the samples, and the quality status of recombinant human interferon α2a injections was evaluated by statistical analysis of the results. Results: All 28 bat-ches of the injections were qualified using the statutory testing methods. The exploratory studies showed that if the specific activity was determined, the qualified rate was only 87. 0%. All 7 batches of drug substances were qualified using the statutory testing methods. The exploratory studies showed that if the related protein was determined, the qualified rate was 57. 1%. Conclusion:At present the quality of recombinant human interferonα2a injections is generally good. The current standards are feasible;however, improvement is still needed. Specific activity determination should be supplemented the standards for drug products and related protein determination should be supplemented the standards of drug substances.
10.Role of angiotensinⅡin the changes of MMP-9 and TIMP-1 mRNA expressions in high glucose-induced mesangial cells of rat
Hai-Yan LI ; Ying GUO ; He-Lin DING ; Zu-Zhi FU ;
Chinese Journal of Endocrinology and Metabolism 1985;0(02):-
High glucose stimulated angiotensinⅡ(ATⅡ) production in mesangial cells of rat.Both high glucose and ATⅡdecreased expressions of matrix metalloprotein-9 (MMP-9) mRNA and MMP-9/tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA ratio and increased TIMP-1 mRNA expression in mesangial cells of rat,which could be reversed by an ATⅡreceptor blocker,Saralasin.