Biomedical subjects
Publications and source records attributed to Li Zhang.
Molecule-targeting agents inhibit the proliferation of tumor cells by the molecular biological differences between tumor cells and normal cells, and finally kill tumor cells. This article introduces several molecule-targeting agents that are currently under clinical trials now.
Chemotherapy of the elderly patients with III B/IV stage non-small cell lung cancer till remains controversial. We retrospectively reviewed the recent literatures, and conclude that single-agent chemotherapy should be the standard therapy of the elderly patients with IIIB/IV stage non-small cell lung cancer.
OBJECTIVE: To investigate the single nucleotide polymorphism 4 (SNP4) of the apolipoprotein A5 (APOA5) gene possible association with coronary heart disease(CHD) and its distribution of in Chinese Han population. METHODS: APOA5 SNP4 genotyping was performed using polymerase chain reaction and Hae III restriction fragment length polymorphism analysis. RESULTS: APOA5 allelic frequencies of T, C were 0.435, 0.565 and 0.374, 0.626 in CHD group and control group, respectively. There is significant difference in allele and genotype frequencies between CHD group and control group (P<0.05). The levels of plasma high density lipoprotein in CHD patients with CC genotype were higher than those in CHD patients with other genotypes (P<0.01). The frequencies of T allele and C allele in Chinese was significantly different from those in Caucasians (0.374 vs 0.663, 0.626 vs 0.337, P<0.01). The C allele was much more common in Chinese population. CONCLUSION: The association is found between the Hae III polymorphism and CHD, There is a significant correlation between the CC genotype of the APOA5 and the levels of plasma high density lipoprotein-cholosteal in the CHD group.
BACKGROUND & OBJECTIVES: B cell non-Hodgkin's lymphoma (B-NHL) in childhood and adolescence is aggressive. Routine CHOP regimen can improve the survival rate of patients with early-stage disease, but its effect on patients with advanced disease was poor. Therefore, it is worthwhile to further investigate how to treat patients with B-NHL at different stages. This study was designed to retrospectively analyze and compare CHOP, CHOP+HD-MTX, and BFM-90 regimens in the survival rate of children and adolescents with B-NHL,and explore the optimal therapeutic strategy and protocols. METHODS: Thirty cases of 3- to 17-year-old untreated patients with B-NHL were enrolled in CHOP group, with 13 in Stage I/II, and 17 in stage III/IV (St Jude staging), all patients received standard CHOP for 2 to 8 cycles, the regimen was repeated every 3 weeks. Eighteen cases of 3- to 14-year-old untreated patients with B-NHL were enrolled in CHOP+HD-MTX group, with 6 in Stage I/II, and 12 in stage III/IV (St Jude staging), all patients received CHOP+HD-MTX and intrathecal injection for 2 to 8 cycles, the regimen was repeated every 4 weeks. Twenty-five cases of 1.5- to 15-year-old untreated patients with B-NHL were enrolled in BFM-90 group, with 7 in Stage I/II,and 18 in stage III/IV (St Jude staging). The patients with stage I/II disease received A schema alteration with B schema of BFM-90 regimen for 4 to 6 cycles, while the patients with stage III/IV disease received AA schema alteration with BB schema of BFM-90 regimen for 6 cycles, the interval of cycles was 18-21 days. The survival rates were evaluated by Kaplan-Meier method. RESULTS: In CHOP group,complete response (CR) rate was 70% (21/30), and partial response (PR) rate was 13% (4/30). In CHOP+HD-MTX group, CR rate was 83%, PR rate was 16%. In BFM-90 group, CR rate was 96% (24/25), and PR rate was 4% (1/25). The hematologic toxicity incidence was higher in BFM-90 group than in the other 2 groups. In CHOP group, the overall 2-year survival rate was 52.79% (72.73% for Stage I/II, and 37.82% for stage III/IV). In CHOP+HD-MTX group, the overall 2-year survival rate was 55.56 % (83.33 % for Stage I/II, and 41.67 % for stage III/IV). There was no significant difference between CHOP group and CHOP+HD-MTX group in survival rate (P=0.78). In BFM-90 group,2-year event-free survival rate (EFS) was 84.01 % (100% for Stage I/II, and 77.04 % for stage III/IV). The differences in survival rate between BFM-90 group and CHOP group, CHOP+HD-MTX group were both significant (P=0.013, and P=0.034). CONCLUSION: BFM-90 regimen can greatly improve the survival rate of children and adolescents with B-NHL, especially of patients with advanced NHL. CHOP, and CHOP+HD-MTX regimens work better for the early stage patients, but produce low survival rate for patients with advanced NHL. A high intensive chemotherapy like BFM-90 regimen is necessary for children and adolescents with advanced B-NHL.
AIM: To observe the effect of adenosine A, receptor antagonist on synaptic transmission in the dentate gyrus of hippocampus and its relations with NMDA receptor. METHODS: Using electrophysiological technique to record the long-term potentiation (LTP), the relation between selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and NMDA receptor agonist/antagonist, in both basic synaptic transmission and 200 Hz high-frequency stimulation (HFS) induced LTP of the dentate gyrus of hippocampus in anesthetized rats, was studied. RESULTS: DPCPX (6 mg x L(-1), 5 microL, icv) or NMDA (0.2 mg x L(-1), 5 microL, icv) was shown not to affect the synaptic transmission in the dentate gyrus in rats. DPCPX was found not to affect the keeping of LTP induced by HFS after icv NMDA. But the basic synaptic transmission and the magnitude of LTP induced by HFS in the dentate gyrus after icv NMDA could be enhanced significantly by icv DPCPX in advance. DPCPX could not affect the magnitude of LTP inhibited by AP5 (0.5 mg x L(-1), 5 microL) NMDA receptor antagonist, but the inhibitory effect of AP5 on LTP could be antagonized by icv DPCPX in advance. CONCLUSION: The selective adenosine A1 receptor antagonist DPCPX could not affect the synaptic transmission in the dentate gyrus of hippocampus, but could significantly enhance the effect of NMDA receptor in both basic synaptic transmission and HFS induced LTP in the dentate gyrus of hippocampus in anesthetized rats.
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OBJECTIVE: To evaluate the outcome of patients with de novo acute leukemia (AL, no AML-M(3)) in CR(1) undergone autologous hematopoietic stem cell transplantation (auto-HSCT) or HLA-identical sibling allogeneic HSCT (allo-HSCT). METHODS: Forty-six AL patients received allo-HSCT and 94 received auto-HSCT in CR(1). The conditioning regimens mainly consisted of TBICy, BuCy and MAC. Cyclosporine plus methotrexate, or cyclosporine alone, or FK506 alone was used for graft-versus-host disease (GVHD) prophylaxis. Among auto-HSCT group, 39 patients received purged autologous bone marrow and 38 received immunotherapy and/or maintenance chemotherapy after transplant. RESULTS: Myeloid reconstitution was achieved in all patients. After a median of 700 (range, 18 approximately 5563) days follow-up, the probabilities of leukemia-free survival (LFS) at 5 year were not significantly different in these two groups: (51.5 +/- 5.4)% for auto-HSCT group and (52.8 +/- 7.6)% for allo-HSCT group (P > 0.05). There was a lower cumulative relapse incidence (RI) [(26.3 +/- 6.9)% vs. (52.0 +/- 5.5)%, P > 0.05] but a significantly higher cumulative transplant-related mortality (TRM) [(37.6 +/- 7.8% vs. (14.4 +/- 4.1)%, P < 0.05] in the allo-HSCT group than in auto-HSCT group. Among auto-HSCT group, the patients received purged autografts and/or post-transplant therapy had significantly better LFS and lower RI (P < 0.05) than those received unpurged autografts or no post-transplant treatments [5-y LFS: (62.8 +/- 6.8)% and (38.4 +/- 8.4)%; RI: (37.7 +/- 6.8)% and (74.2 +/- 8.7)%, respectively]. CONCLUSION: The long-term LFS of auto-HSCT was comparable to that of allo-HSCT in the management of patients with AL in CR(1), because autograft purging and post-transplant treatment can significantly decrease relapse of auto-HSCT patients and auto-HSCT has lower therapy-related toxicities.
To explore the Fas and mdr-1 expression and their correlation in multidrug resistance (MDR), Fas and mdr-1 expressions of bone marrow from 59 patients with newly diagnosed AL before therapy and after complete remission were detected by direct immunofluorescence with flow cytometry and semi-quantitative RT-PCR, respectively. The results showed that in newly diagnosed AL patients, Fas expression in AML was higher than in ALL (P < 0.05), mdr-1 expression in AML and ALL had no difference (P > 0.05), the expressions of Fas and mdr-1 had correlation (r = -0.282, P < 0.05) in AL; the results of simple-variable and multivariable COX survival factor model analysis suggested that Fas and mdr-1 expressions were prognostic factors for the effect of therapy and survival. Log rank test, comparing the groups of Fas(+) with Fas(-), mdr-1(+) with mdr-1(-), demonstrated that the CR rates and median remission time of every two groups had significant difference. It is concluded that in AL, Fas and mdr-1 expressions have high correlation with the effect of treatment, Fas expression probably is one of the favorable prognostic factors, mdr-1 is an unfavorable prognostic and less effective factor.
OBJECTIVE: To assess the effectiveness of follicular aspiration in selection phase of follicle growth of the patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization-embryo transfer (IVF-ET). METHODS: Thirteen infertile patients with PCOS who previously failed IVF-ET associated with ovarian hyperstimulation syndrome (OHSS), served as control group, were asked to undergo new IVF cycles (follicular aspiration group) with ultrasound-guided transvaginal follicular aspirations in the selection phase (diameter 9 - 10 mm) of follicle growth, with a total of 13 cycles both. No more than 10 follicles were selected. Clinical and endocrinological parameters were monitored. RESULTS: In follicular aspiration group, the average number of follicle >or= 12 mm in diameter and serum estradiol level were 16 +/- 4 and (9899 +/- 1431) pmol/L respectively, which were significantly lower than 29 +/- 8 (P < 0.001) and (15,544 +/- 1767) pmol/L (P < 0.001) in control group. No moderate-severe OHSS occurred in follicular aspiration group, while 9 out of 13 (69%) occurred in control group. Oocyte retrieval rate, maturation rate, fertilization rate and cleavage rate in follicular aspiration group were greatly higher than those in control group. CONCLUSIONS: Follicular aspiration in selection phase of follicle growth associates with reduced dominant follicle numbers and estradiol level on the day of hCG injection and moderate-severe OHSS incidence in patients with PCOS undergoing IVF-ET.
AIM: To construct inducible expression vector for human granzyme B gene and express it in Hela cell line. METHODS: Human active granzyme B gene was obtained by PCR and cloned into the inducible expression vector pIND. The resulting expression vector, together with a helper plasmid pVgRXR, was stably transfected into Hela cells using Lipofectamine 2000. The transfected cells were selected in medium containing G418 and zeocin. The resistant cells were induced with ponasterone A, and the optimal concentration of ponasterone A and time of induction were determined by immunocytochemical staining. Then the effects of the expressed granzyme protein on Hela cells were detected by MTT colorimetry and cytoskeletal staining. RESULTS: The Hela cells that inducibly expressed human active granzyme B were obtained. Induction with 30 micromol/L ponasterone A for 5 days caused the strongest expression of granzyme B. The induced cells appeared as either multinucleate giant cells or pyknotic small cells, and their growth was inhibited. Further analysis demonstrated cytoskeletal abnormality of multinucleate giant cells. CONCLUSION: The establishment of inducible expression system for active granzyme B lays the foundation for further research on biological function of granzyme B.
BACKGROUND: The Taq/B, Msp/ and I405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this study, we investigated the associations between these 3 polymorphisms of CETP gene and variations in plasma lipid and lipoprotein levels in patients with coronary heart disease (CHD). METHODS: Genomic DNA was extracted from leukocytes of 203 CHD patients and 100 control subjects using the salting out method. Genotyping of the CETP gene was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Statistical analysis was conducted using the SPSS 10.0 software package. RESULTS: The distribution of allele and genotype frequencies of the Taq/B, MspI, and I405V polymorphisms was similar in the CHD patient group and the control group. The B1B1 genotype of the Taq/B polymorphism was associated with significantly higher TC (P=0.039) and LDL-C (P=0.044) levels than the B2B2 genotype in CHD patients, and with significantly higher LDL-C (P=0.034) levels than the B2B2 genotype in controls. Homozygotes of the I405V polymorphism exhibited significantly higher HDL-C levels than VV homozygotes among control subjects (P=0.023). In male CHD patients with unambiguously assigned haplotypes, B2-M2-V/B2-M2-I patients demonstrated significantly higher HDL-C concentrations than B1-M2-V/B1-M2-I (P=0.023) and B1-M2-V/B1-M2-V patients (P=0.047). CONCLUSIONS: Genetic variations in the CETP gene may account for a significant proportion of the differences in plasma lipid and lipoprotein concentrations among the general population. The B1B1 genotype of the Taq/B polymorphism is probably a genetic risk factor for CHD in the study population.
AIM: To study whether extract of Ginkgo biloba (EGb) can protect against atherosclerosis. METHODS: Confluent monolayers of bovine coronary endothelial cells (BCECs), bovine coronary smooth muscle cells (BCSMCs), and cocultures of the two were incubated with medium containing VEGF and/or EGb, and flux of 125I-labeled oxidized low density lipoprotein (ox-LDL) across the monolayers was measured. RESULTS: Incubation with VEGF significantly increased the permeability of BCEC monolayers to 125I-ox-LDL in a time- and concentration-dependent manner, but had no effect on permeability of BCSMCs or endothelial cells-smooth muscle cells cocultures. EGb significantly inhibited the VEGF-induced hyperpermeability of BCECs. CONCLUSION: VEGF was important in the formation and development of atherosclerosis. The inhibition of VEGF-induced permeability by EGb suggests that extracts of Ginkgo biloba leaves may have important clinical applications in the treatment of cardiovascular diseases.
BACKGROUND: Corticosteroid treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has been one of the most controversial clinical issues in critical care. Although the administration of high-dose corticosteroids does not benefit patients with early septic shock and ARDS, recent clinical trials have indicated that treatment with relatively low-dose corticosteroids (2 to 3 mg/kg/day of methylprednisolone or equivalent) may improve outcome when used for late ARDS or persistent septic shock. The underlying mechanism was not fully clarified. Whether the administration of corticosteroids can arrest neutrophil-driven organ injury once started remains to be elucidated. OBJECTIVE: To observe the effects of hydrocortisone (HC, 6 mg/kg) on oxygen free radicals (OFR) released by PMN and pulmonary pathological changes in rat ALI model induced by lipopolysaccharide (LPS), to investigate the possible mechanism through which corticosteroids exert protective effect on ALI. METHODS: A rat model of ALI was induced by peritoneal injection of 2 x 10(12) Escherichia coli/kg. Fifty-six rats were randomly divided into three groups: normal control group, LPS group and HC group (6 mg/kg). Samples were collected 2 h, 4 h and 6 h after giving LPS to LPS and HC group (6 h after giving normal saline in normal control group) to measure the level of OFR released by PMN using chemiluminescence method based on lumino, and to compae of pulmonary pathological changes among the three groups. RESULTS: Pathological examination with light microscope in LPS group showed thickened pulmonary interstitia, inflammatory cell infiltration, edema and hemorrhage, which were in accordance with the features of ALI. There were significant differences in the release of OFR by PMN among the three groups (P < 0.01). The level of OFR released by PMN in LPS group was significantly higher than that of the control group, and continued to increase during the observation period (2 - 6 h after LPS). The release of OFR by PMN in HC group was significantly suppressed as compared with LPS group, which was peaked at 4 h after LPS injection (to 98.2%); there were also significant differences in the grades of ALI pathologic changes among the three groups (P < 0.01). The grades of ALI pathologic changes in LPS group were significantly increased when compared with the normal control group (P < 0.05) while significantly decreased in HC group as compared with LPS group (P < 0.05). CONCLUSION: It was demonstrated in the LPS induced ALI model that OFR might play an important role in onset of ALI. Intervening with HC (6 mg/kg) treatment could ameliorate the lung injury and exert significant and sustained suppression on the release of OFR by PMN, showing that HC has a protective effect on LPS induced ALI and its theraputic effect occurs possibly through suppression on the release of OFR by PMN.
AIM: To determine the effect of lysophosphatidylcholine (LPC) on the expression of vascular endothelial growth factor (VEGF) in human umbilical veins endothelial cell line (ECV304) and the inhibitory effect of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-beta-D-glucoside (ST I) in vitro. METHODS: Exposure to 2.5 mg x L(-1) LPC or LPC + ST I for 24 hours, VEGF protein was determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile, VEGF mRNA expression in ECV304 was examined by in situ hybridization. VEGF165 mRNA was examined by RT-PCR and Realtime RT-PCR. RESULTS: LPC upregulated VEGF protein and VEGF mRNA expression in the ECV304 cells. ST I was shown to markedly inhibit the LPC-induced increase of VEGF protein and VEGF165 mRNA (P < 0.001). CONCLUSION: LPC can induce a strong expression of VEGF in ECV304 cells and ST I can inhibit it.
AIM: To investigate the biodistribution and the hepatocytes targeting of cationic liposome containing 3beta[N-( N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and surface-modified liposomes with sterylglucoside (SG) and polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE). METHODS: Cationic liposomes (CL) composed of DC-Chol and dipalmitoylphosphatidylcholine (DPPC), SG/PEG modified cationic liposome (SG/PEG-CL), both contained trace 3H-cholesterol (3H-Chol) as radiolabel, were prepared. The liposomes encapsulating 125I-labled antisense oligodeoxynucleotide (125I-asODN) (SG/PEG-CL-asODN) were also prepared. The biodistribution of CL, SG/PEG-CL, SG/PEG-C2-asODN as well as 125I-asODN solution, were studied. The radioactivities in hepatocytes and non-hepatocytes after administration of CL and SG/PEG-CL were determined by infuseing method. RESULTS: CL and SG/PEG CL significantly aggregated in liver. The distribution of SG/PEG CL was significantly higher in hepatocytes (P < 0.01) and lower in non-hepatocytes (P < 0.01) than that of CL. The concentrations of SG/PEG-CL-asODN in liver and spleen were significantly higher than that of asODN solution (P < 0.01). CONCLUSION: Cationic liposome modified with SG/PEG changed the distribution of asODN. Cationic liposome can target hepatocytes more effective after being modified with SG.
OBJECTIVE: To observe the effect of tetramethylpyrazine (TMP) on lipopolysaccharides (LPS) induced macrophage cyclo-oxidase-2 (COX-2) gene expression and activity in RAW264.7 mice, and to further investigate the effect and mechanism of TMP on LPS induced apoptosis of cardiac myocytes in suckling mice. METHODS: RT-PCR and Western Blot (WB) were used to investigate the macrophage COX-2 gene expression, ELISA was used to measure its activity, fluorescence microscopy was used to determine the apoptosis of murine neonatal cardiac myocyte, and fluorescence spectrophotometry was used to detect the concentration of intracellular calcium ion (Ca2+). RESULTS: TMP of 10(-6) mol/L could significantly reduce the COX-2 mRNA and protein expression (P < 0.05), in 10(-5) mol/L and 10(-4) mol/L could significantly decrease the COX-2 expression (P < 0.01) stimulated by LPS, but couldn't influence the activity of COX-2 by different TMP concentration. TMP in 10(-5) mol/L could significantly lower the concentration of intracellular Ca2+ in cardiac myocyte, and antagonize the LPS induced apoptosis of cardiac myocyte in suckling mice (P < 0.05). CONCLUSION: TMP has the pharmacological effect in inhibiting LPS induced macrophage COX-2 expression and apoptosis of cardiac myocyte in suckling mice.
AIM: To study the morphology, particle size distribution and biological reliability of the norcantharindin (NCTD)-loaded microemulsion and pharmacokinetics of the W/O norcantharidin-loaded microemulsion in mice. METHODS: The concentration of NCTD in plasma and tissues were determined by GC method. The data obtained were processed using 3P87 program. RESULTS: The mean particle diameter of microemulsion was (44 +/- 9) nm. The concentration-time curve of NCTD-loaded microemulsion and NCTD injection was fitted to a two-compartment model. At the same dosage, the pharmacokinetic study for NCTD-loaded microemulsion showed the NCTD microemulsion had relatively longer circulating time in mice. Area under the curve of concentration versus time (AUC), mean residence time (MRT) and half life (T1/2) for microemulsion and injection were (29.7 +/- 0.9) mg x h x L(-1), (9.25 +/- 0.09) mg x h x L(-1), (110 +/- 11) h, (86.7 +/- 0.8) h, (103 +/- 12) h, (42 +/- 4) h, respectively. Targeting index of NCTD microemulsion in liver and kidney in mice were 0.43 and 0.12 after iv NCTD-loaded microemulsion. The effects of biological reliability was not significantly different between NCTD microemulsion and NCTD injection in vivo and in vitro. CONCLUSION: The liver targeting absorptive capability of NCTD-loaded microemulsion was enhanced and the release time was extended compared with NCTD injection. While the microemulsion vehicles could decrease the kidney distribution of NCTD.