2.Clinical observation and prevention of side reaction of high dose methotrexate in the treatment of leukemia
Ying LI ; Song GAO ; Fanli HUA ; Yangjiong WU
Clinical Medicine of China 2014;30(9):964-966
Objective To analyze the clinical efficacy,adverse events and corresponding preventive measures of high dose methotrexate in the treatment of acute lymphoblastic leukemia(ALL).Methods Ninety-two patients with ALL who hospitalized in Heamotology Department of Jinshan Hospital Affiliated to Fudan University were randomly divided into observation group and control group,and each group had 46 cases.Patients in observation group were given high dose melhotrexate + vincristine + cytoxan + pirarubicin chemotherapy treatment,and in control group were given soft red enzyme + vincristine + metacortan dracin + L-asparaginase treatment.The clinical efficacy,adverse events and the required course of remission of two groups were compared.Results The total effective rate in the observation group was 84.78%,while it was 80.43% in the control group,and there was no statistically significant difference (x2 =0.45,P > 0.05).The average remission was (1.26 ± 0.28) in the observation group,while (1.31 ± 0.31) in the control group,and no significant difference was observed (t =2.13,P > 0.05).The complete remission rate of initial treatment,retreatment and refractory were 75.00% (24/32),50.00% (4/8) and 33.33% (2/6) respectively in observation group,while 76.67% (23/30),50.00% (4/8) and 25.00% (2/8) respectively in control group,and there was no statislically significant difference between two groups (x2 =0.98,P >0.05).The rate of bone marrow suppression in the observation group(23.91%) was lower than that in the control group(43.48%),while the rate of liver and kidney injury(54.35%) was higher than that inthe control group(17.39%),which showed significant difference (P < 0.05).The survival rate of 5 years in observation group was 67.39%,while 45.65% in control group,and there was statistically significant difference between two groups (P < 0.05).Conclusion The high dose methotrexate in the treatment of acute lymphoblastic leukemia was proved to be effective and the adverse reactions could be tolerated.
3.Periphery analgesic effect of myricetin on a rat model of inflammatory pain
Ying SONG ; Yongmei ZHANG ; Jie XU ; Rong HUA
Chinese Pharmacological Bulletin 2015;(8):1108-1111
Aim To investigate the periphery analge-sic effect of myricetin on a rat model of inflammatory pain and the mechanism. Methods Rat models of in-flammatory pain were induced by complete Freund ’ s adjuvant ( CFA) injection in left hindlimb plantar cen-ter. The thermal withdrawal latency ( TWL) was meas-ured before and after CFA or myricetin treatment. Elec-trophysiological method was used to identify the effect of myricetin on the action potential frequency and the voltage dependent potassium channel currents in small DRG neurons. Results Rats with CFA injected showed thermal hyperalgesia ( P <0. 05 ) and TWL in-creased significantly after myricetin intraperitoneally in-jected ( P <0. 05 ) . Current clamp recording showed the action potential frequency of small DRG neurons in rats was inhibited by myricetin ( P<0. 01 ) and voltage calmap recording showed the inhibitory effect of myr-icetin was enhanced by calcium depended potassium channel currents ( P<0. 05 ) . Conclusion Myricetin exerts periphery analgesic effect by enhancing calcium depended potassium channel currents and inhibiting excitability of small neurons of dorsal root ganglion.
4.Surgical revascularization of patients with chronic total coronary occlusion combined with diffuse distal atherosclerosis
Ying FANG ; Chengxiong GU ; Hua WEI ; Wei SONG ; Zhen WU
Chinese Journal of Geriatrics 2010;29(6):452-455
Objective To evaluate the effect of off-pump coronary endarterectomy (CE) plus off-pump coronary artery bypass grafting (off-pump CABG) on patients with chronic total occlusion (CTO) combined with diffuse distal atherosclerosis. Methods From October 2006 to August 2009,65 CTO patients with 176 angiographically confirmed vascular stenosis or occlusive lesions, 70 of which were complete occlusion, underwent off-pump CABG. During the operation, diffuse intimal thickening distal to occlusive lesion was found, and blood flow of the bridges was unfavorable.Results Therefore endarterectomy was performed, followed by CABG. The blood flow in the bridges were 2-10 ml/min versus 14-37 ml/min before versus after endarterectomy. Pulsatility index (PI) was 5.1-15.6 versus less than 5 before versus after endarterectomy. Left ventricular ejection fraction was also improved significantly [before operation: (0.47±0.12)%, after operation: (0. 52±0.15)%, t=2.17, P<0.05]. Peri-operative myocardial infarction occurred in 2 cases, but without significant cardiac homodynamic changes. And 23 patients underwent coronary angiography to evaluate graft patency 3-18 months after operation, all of them had favorable blood flow. Conclusions It is feasible to perform off-pump CABG plus coronary endarterectomy for patients of chronic coronary total occlusion combined with diffuse distal atherosclerosis. This treatment is safe and effective.
5.Effect of Actinidia chinensis planch polysaccharide on the growth and apoptosis, and p-p38 expression in human gastric cancer SGC-7901 cells.
Wen-Ying SONG ; Guan-Hua XU ; Guang-Ji ZHANG
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(3):329-333
OBJECTIVETo investigate the effect of Actinidia chinensis Planch polysaccharide (ACPS) on the growth and apoptosis of human gastric cancer SGC-7901 cells, and to explore the effect of SGC-7901 cells on p-p38 expression.
METHODSThe inhibition rates at different concentrations of ACPS on SGC-7901 cells at 24, 48, and 72 h were detected using CCK-8 method. Apoptosis ratios in SGC-7901 were determined by flow cytometry after 48-h treatment of different concentrations of ACPS. The expression of pro-caspase-9, PARP, and p-p38 in SGC-7901 cells after treated by different concentrations of ACPS was detected using Western blot. The expression of pro-caspase-9, PARP, and p-p38 was detected after SGC-7901 cells were pre-treated by p38 specific inhibitor.
RESULTSCompared with the control group, the optical density of SGC-7901 cells decreased after treated by 1, 2.5, 5, and 10 mg/mL ACPS (P < 0.05). Meanwhile, the longer the acting time, the lower the optic density (P < 0.01). IC50 was 7.43 mg/mL at 24 h; 3.88 mg/mL at 48 h, and 1.32 mg/mL at 72 h respectively. ACPS suppressed the protein expression of pro-caspase-9 (P < 0.01) and up-regulated the expression of PARP (89KD) (both P < 0.01). Further study showed that the protein expression of p-p38 was up-regulated in SGC-7901 cells treated by ACPS of different concentrations at 24 h (P < 0.05). The expression of phosphorylation p38 and the ACPS induced apoptosis of SGC-7901 cells could be inhibited after treated by specific inhibitor for 2 h.
CONCLUSIONSACPS could inhibit the growth of SGC-7901 cells and induce apoptosis. The underlying mechanism of inducing apoptosis was partially due to activating the p38MAPK path and further activating Caspase9 and PARP, finally leading to cell death.
Actinidia ; chemistry ; Apoptosis ; drug effects ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism ; Polysaccharides ; pharmacology ; Stomach Neoplasms ; metabolism ; pathology ; p38 Mitogen-Activated Protein Kinases ; metabolism
6.Rapid Detection of Down Syndrome by Gene Diagnosis Using Short Tandem Repeat Polymorphisms
hui, CHEN ; jian-hua, LIAN ; guo-ying, SONG ; hua, QI ; qin-xian, ZHANG ; xiao-wen, LI
Journal of Applied Clinical Pediatrics 2006;0(14):-
Objective To set a rapid,simple gene diagnosis method for Down syndrome.Methods Three short tandem repeats(D21S11,D21S1270,D21S1437)loci in or near Down syndrome critical region(DSCR) were analyzed and detected by polymerase chain reaction and DNA quantitative analysis in 11 core ancestry.Results There were four types by DNA quantitative analysis to different individuals at a short tandem repeats(STR) locus.In type one,a homozygote of one allelic gene was detected.In type two,a normal heterozygote of two allelic genes was found,the content or two DNA electrophoresis bands was approximately 1∶1.In type three,a Down syndrome patient of two allelic genes was discovered.The quantity of two electrophoresis bands was nearly 2∶1.In type four,the patient showed three DNA electrophoresis bands which the content was approximately 1∶1∶1.Conclusion A rapid gene diagnosis and prenatal diagnosis method for Down syndrome can be used for quantitative analysis of STR polymorphism loci.
7.Effects of overexpression of human vascular endothelial growth factor 165 and human tissue inhibitor of metalloproteinase 1 on rats with myocardial infarction
Yanqiu SONG ; Yongmin MAO ; Hua GENG ; Ying ZHANG ; Ying SHI ; Min REN ; Meilin XU ; Zhigang GUO
Chinese Journal of Emergency Medicine 2021;30(3):293-300
Objective:To investigate the effects of recombinant adenovirus with human vascular endothelial growth factor 165 (Ad-hVEGF 165) and recombinant adenovirus with human tissue inhibitor of metalloproteinase 1 (Ad-hTIMP-1) on rats with myocardial infarction (MI) and its mechanism. Methods:A total of 30 healthy 8-week-old male Wistar rats were randomly divided into 5 groups: sham-operated group (sham), virus control group (Ad-Track), Ad-hVEGF 165 group, Ad-hTIMP-1 group and Ad-hVEGF 165+Ad-hTIMP-1 group (hVEGF 165+hTIMP-1) ( n=6 per group). Except the sham group, all rats were ligated the left anterior descending coronary artery to induce MI model with ST-segment elevation and Q waves or T-wave inversion on electrocardiogram and local myocardial whitening. The corresponding recombinant adenovirus comprising 100 μL (1×10 10 VP/100 μL) combined with NaCl solution was injected into the myocardial infarction area at four points respectively. The sham group received no treatment. After 4 weeks, all rats were sacrificed after echocardiography was completed and heart tissues were collected. The expression of hVEGF 165 and hTIMP-1 were detected by immunohistochemistry. The mRNA expression of apoptosis-related factors were detected by real-time PCR. The protein expression of apoptosis-related factors were detected by immunohistochemistry. Differences between groups were determined by One-way analysis of variance. Multiple comparisons between groups were performed using the least significant difference t-test. Results:(1) Both heart rate (HR) (480.83±24.09) beats/min, left ventricular end-diastolic dimension (LVEDD) (6.88±0.44) mm and left ventricular end-systolic dimension (LVESD) (4.85±0.42) mm were increased in the Ad-Track group than those in the sham group (433.16±17.86) beats/min, (6.20±0.45) mm, (4.06±0.70) mm (all P<0.05), and left ventricular ejection fraction (LVEF) (62.70±3.17) % and left ventricular fractional shortening (LVFS) (29.52±1.88) % were significantly decreased in the Ad-Track group than those in the sham group (72.78±5.44)%, (29.52±1.88) % (both P<0.01). Compared with the Ad-Track group, LVEF (71.50±6.23) % and LVFS (36.17±5.27) % in the hVEGF 165-hTIMP-1 group were significantly increased (both P<0.01), and LVEDD (6.22±0.39) mm and LVESD (4.13±0.23) mm were decreased (both P<0.05). LVEF and LVFS in the hVEGF 165-hTIMP-1 group were increased significantly than those in the Ad-hVEGF 165 group (64.65±4.00) %, (30.95±2.57) % (both P<0.05). The mRNA expression of BCL2-associated X protein (Bax), cysteine aspartate specific proteinase 3 (Caspase-3) and BCL-xL/BCL-2-associated death promoter (Bad) in the hVEGF 165-hTIMP-1 group were decreased than those in the Ad-Track group ( P<0.01 or P<0.05), and B-cell lymphoma/leukemia-2 (Bcl-2) in the hVEGF 165-hTIMP-1 group were increased than those in the Ad-Track group ( P<0.01). The mRNA expression levels of Bax and Caspase-3 in the hVEGF 165-hTIMP-1 group were decreased than those in the Ad-hVEGF 165 group (both P<0.05). There was no statistically difference in the mRNA expression of Bax, Caspase-3, Bad, and Bcl-2 between the hVEGF 165-hTIMP-1 group and the sham group (all P>0.05). The protein expression of Bax and Caspase-3 in the hVEGF 165-hTIMP-1 group were significantly decreased than those in the Ad-hVEGF 165 group, the Ad-hTIMP-1 group and the Ad-Track group (all P<0.01), and the protein expression of Bcl-2 in the hVEGF 165-hTIMP-1 group was increased than those in the Ad-hVEGF 165 group, the Ad-hTIMP-1 group and the Ad-Track group (all P<0.05). There were no statistically differences in the protein expression of Bax, Caspase-3 and Bcl-2 between the hVEGF 165-hTIMP-1 group and the sham group (all P>0.05). Conclusions:Ad-hVEGF 165 and Ad-hTIMP-1 can improve cardiac contractile function of MI rats and the beneficial effects are largely attributable to inhibiting myocyte apoptosis. The combination of hVEGF 165 and hTIMP-1 may have a synergistic effect on MI.
8.Pharmacokinetics of salvianolic acid A after single intravenous administration in Rhesus monkey.
Jun-ke SONG ; Wen ZHANG ; Wei-ku ZHANG ; Zhang-ying FENG ; Tao XIE ; Guan-Hua DU
Acta Pharmaceutica Sinica 2015;50(9):1142-1147
Salvianolic acid A (Sal A) is one of the most effective compounds isolated from the root of Salvia miltiorrhiza. Up to now, several studies regarding the pharmacokinetic profiles of Sal A have been reported, however there is no such study reported in monkeys, the species which is more similar to human. The aim of this study is to develop a LC-MS method for the determination of Sal A in monkey plasma and apply it to the pharmacokinetic studies of monkeys. After single intravenous administration of Sal A, the plasma concentration-time curves were observed and the main pharmacokinetic parameters were calculated. The plasma concentration at 2 min (C2 (min)) values were (28.343 ± 6.426), (45.679 ± 12.301) and (113.293 ± 24.360) mg x L(-1) for Rhesus monkeys treated with Sal A at 2.5, 5 and 10 mg x kg(-1). The area under the concentration-time curve (AUC(0-∞)) values were (3.316 ± 0.871), (5.754 ± 2.150) and (13.761 ± 2.825) μg x L(-1) x h, respectively. Furthermore, this method was improved and applied to the simultaneous determination of Sal A, Sal B and Sal C, which provided useful information for preclinical studies and clinical trials of Sal A, Sal B and Sal C.
Administration, Intravenous
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Animals
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Caffeic Acids
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pharmacokinetics
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Chromatography, Liquid
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Drugs, Chinese Herbal
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pharmacokinetics
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Lactates
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pharmacokinetics
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Macaca mulatta
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Mass Spectrometry
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Plant Roots
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chemistry
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Salvia miltiorrhiza
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chemistry
9.Study of the relationship between ALOX5AP gene polymorphisms and the genetic susceptibility of ischemic cerebrovascular diseases by SNaPshot minisequencing method
Congcong SHI ; Ying HE ; Dongzhi YANG ; Tao LI ; Guoying SONG ; Hua QI ; Yuming XU ; Hong ZHENG
Chinese Journal of Neurology 2012;45(3):163-168
Objective To explore associations between SG13S114A/T and SG13S32A/C polymorphisms of ALOX5AP gene and the genetic susceptibility of ischemic cerebrovascular diseases (ICVD) in Henan Han population.Methods Two hundred and forty-six ICVD patients and 245 healthy controls were recruited from Han population in Henan province. Polymorphisms of SG13S114A/T and SG13S32A/C in ALOX5AP gene were genotyped in these samples by SnaPshot minisequencing method.Each genotype frequency and allele frequency were statistically analyzed and compared between ICVD group and control group using SPSS16.0 software.Haplotype and linkage disequilibrium were analyzed by SHEsis software.Results The SG13S114 AA genotype frequency ( 18.7% ) and A allele frequency (41.3%) in ICVD group were significantly higher than those in control group (9.0% and 32.7%,respectively; P =0.002 and P =0.005 ).It was also found that in male ICVD group and in younger ICVD group ( <50 years old),the SG13S114 AA genotype frequencies (22.1% and 22.0%,respectively) and A allele frequencies (42.1% and 42.7%,respectively) were significantly higher than those in male control group and younger control group (SG13S114 AA genotype:9.0% and 8.9% ; P =0.010 and P =0.006,respectively) ;A allele frequencies,34.0% and 32.0% ; P =0.048 and P =0.020,respectively.Finally,the prevalence of A-A haplotype in ICVD group was significantly higher than that in control group(30.4% vs 23.5%,OR =1.419,95% CI 1.068-1.885,P =0.015).T-C haplotype frequency of ICVD group was significantly lower than that in control group (22.0% vs 28.8%,OR =0.698,95% CI 0.523-0.932,P =0.014 ).Conclusions The A allele in SG13S114 loci of ALOX5AP may be a genetic risk factor for ICVD in Han population in Henan province.The association is predominant in ICVD patients of male and younger than 50 years old.Maybe A-A haplotype increases the risk of ICVD and T-C haplotype and has a protective effect against ICVD in Henan Han population.
10.Selective cyclooxygenase-2 inhibitor celecoxib could sensitize B-cell-originated lymphoma cell lines ;to epirubicin via down-regulation of MDR-1 mRNA and Bcl-2 mRNA expression
Fanli HUA ; Lingyan WANG ; Xin ZHAO ; Ying LI ; Yangjiong WU ; Song GAO
China Oncology 2015;(6):432-437
Background and purpose: It has been demonstrated that cyclooxygenase-2 (COX-2) is over-expressed in some subtypes of non-Hodgkin’s lymphoma (NHL), and COX-2 correlates with the expression of P-glycoprotein and Bcl-2, which may contribute to chemotherapy-resistance in NHL. The purpose of this study was to investigate the expression of COX-2 in B-cell lymphoma cell lines and the potential mechanisms of celecoxib, a selective COX-2 inhibitor, to sensitize lymphoma cell lines to epirubicin. Methods: Quantitative fluorescent real-time poly-chain-reaction (qRT-PCR) and Western blot were employed to determine the expression of COX-2 in Raji, Jeko-1 and Namalwa cell lines, as well as in peripheral blood B cells from normal controls. Cell lines were treated with celecoxib at gradient concentrations, followed by the detection of cell viabilities by cell counting kit-8 (CCK-8).Meanwhile, the changes in expression of MDR-1 mRNA and Bcl-2 mRNA before and after celecoxib treatment were determined by qRT-PCR. Raji cells were treated with epirubicin alone or in combination with gradient concentrations of celecoxib for 72 h, then CCK-8 was used to analyze whether celecoxib sensitize Raji cells to epirubicin. Results:Neither lymphoma cell lines nor normal B cells expressed detectable COX-2 in this study. Celecoxib inhibited the proliferation of the 3 lymphoma cell lines, and the mRNA expressions of MDR-1 and Bcl-2 were decreased by celecoxib in a concentration-dependent manner, except for that MDR-1 was undetectable in Jeko-1 cells. In addition, celecoxib sensitized Raji cells to epirubicin, indicating a synergistic anti-tumor effect between the two agents. Conclusion:Selective COX-2 inhibitor celecoxib down-regulates the expressions of MDR-1 mRNA and Bcl-2 mRNA in B-cell-originated lymphoma cell lines, and sensitizes Raji cells to epirubicin.