Spatial epidemic characteristics of human brucellosis in Gansu Province from 2016 to 2020 / 中华地方病学杂志

Objective:To learn about the epidemic dynamics and spatial epidemic characteristics of human brucellosis in Gansu Province.Methods:Data on human brucellosis in Gansu Province reported by China Disease Control and Prevention Information System from January 2016 to December 2020 were collected and analyzed by descriptive epidemiology and spatial clustering analysis.Results:A total of 10 025 cases of human brucellosis were reported in Gansu Province from 2016 to 2020, with a statistically significant difference in incidence rate between years (χ 2 = 242.86, P = 0.001). The incidence was the lowest in 2018 (6.03/100 000), and the highest in 2020 (11.39/100 000). The reported cases were concentrated in 45 - 55 years old, accounting for 34.52% (3 461/10 025); the male to female ratio was 2.91 ∶ 1.00 (7 458/2 567); farmers were the main occupation, accounting for 82.11% (8 232/10 025). Among the 86 counties (cities, districts) in Gansu Province, Yongchang County had the highest number of reported cases in 2020 (339 cases), and Sunan Yugur Autonomous County had the highest incidence in 2020 (190.89/100 000). Spatial autocorrelation analysis showed that there was significant spatial positive correlation between the incidence rate of human brucellosis in Gansu Province from 2016 to 2020 (global Moran's I > 0, Z > 1.96, P < 0.05), showing a spatial clustering distribution. The high-high clustering areas were concentrated in Yongchang County and Sunan Yugur Autonomous County. Conclusion:In Gansu Province, the main population of human brucellosis is middle-aged male farmers, and the incidence of brucellosis is spatially clustered.

Inhibition of CaMKII alleviates myocardial ischemia?reperfusion injury by reducing mitochondrial oxidative stress in isolated perfused rat heart / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of calcium/calmodulin-dependent protein kinase II (CaMKII) in myocardial ischemia-reperfusion (IR) injury in isolated perfused rat heart and explore the underlying mechanisms.</p><p><b>METHODS</b>An ischemia-reperfusion (IR) model was prepared using isolated rat hearts perfused with Krebs-Henseleit solution were randomly divided into control group, 2.5 µmol/L KN-93 group, IR (induced by ischemia for 45 min followed by reperfusion for 120 min) group and KN-93+IR group. The myocardial performance was evaluated by assessing the left ventricular pressure. Lactate dehydrogenase (LDH) activity and cTnI content in the coronary flow and the infarct size were determined to evaluate the myocardial injury. The phosphorylation of CaMKII (p-CaMKII) and PLN (p-PLN) and oxidation of CaMKII (ox--CaMKII) were measured with Western blotting. The activity of mitochondrial superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined using ELISA.</p><p><b>RESULTS</b>Compared with the control group, KN-93 treatment at 2.5 µmol/L produced no significant effects on cardiac function or performance in rat hearts without IR injury. Myocardial IR injury significantly decreased myocardial performance and mitochondrial SOD activity in the perfused hearts (P<0.01) and caused significantly increased infarct size, LDH activity, cTnI content, expressions of p-CaMKII, ox-CaMKII and p-PLN, and also increased mitochondrial MDA content (P<0.01). KN-93 treatment at 2.5 µmol/L administered before ischemia and before reperfusion markedly attenuated such changes induced by ischemia and reperfusion (P<0.01).</p><p><b>CONCLUSION</b>CaMKII participates in myocardial IR injury in isolated rat heart, and inhibiting CaMKII can alleviate myocardial injury by relieving mitochondrial oxidation stress.</p>

Effect of 2,3-butanedione monoxime on calcium paradox-induced heart injury in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the Effect of 2,3-butanedione monoxime (BDM) on calcium paradox-induced heart injury and its underlying mechanisms.</p><p><b>METHODS</b>Thirty-two adult male SD rats were randomized into 4 groups, namely the control group, BDM treatment control group, calcium paradox group, and BDM treatment group. Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion and the left ventricular pressure (LVP) and left ventricular end-diastolic pressure (LVEDP) were monitored. Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance. Lactate dehydrogenase (LDH) content in the coronary flow was determined. Triphenyltetrazolium chloride staining was used to measure the infarct size, and myocardial cell apoptosis was tested with TUNEL method. Western blotting was used to determine the expression of cleaved caspase-3 and cytochrome c.</p><p><b>RESULTS</b>Compared with the control group, BDM at 20 mmol/L had no effect on cardiac performance, cell death, apoptotic index or the content of LDH, cleaved caspase-3 and cytochrome c at the end of perfusion under control conditions (P>0.05). Calcium paradox treatment significantly decreased the cardiac function and the level of LVDP and induced a larger infarct size (P<0.01), an increased myocardial apoptosis index (P<0.01), and up-regulated expressions of cleaved caspase-3 and cytochrome c (P<0.01). BDM (20 mmol/L) significantly attenuated these effects induced by calcium paradox, and markedly down-regulated the levels of LVEDP and LDH (P<0.01), lowered myocardial apoptosis index, decreased the content of cleaved caspase-3 and cytochrome c (P<0.01), increased LVDP, and reduced the infarct size (P<0.01).</p><p><b>CONCLUSION</b>BDM suppresses cell apoptosis and contracture and improves heart function and cell survival in rat hearts exposed to calcium paradox, suggesting the value of BDM as an potential drug for myocardial ischemia reperfusion injur.</p>

Expression of molecular markers detected by immunohistochemistry and risk of lymph node metastasis in stage T1 and T2 colorecrectal cancers / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the molecular risk factors of lymph node metastasis in stage T1 and T2 colorectal cancers by tissue microarray and immunohistochemistry techniques.</p><p><b>METHODS</b>Two hundred and three patients with stage T1 and T2 colorectal carcinoma who underwent radical surgery from 1999 to 2010 in our department were included in this study. Their clinicopathological data were retrospectively analyzed. Expression of the following 14 molecular markers were selected and assayed by tissue microarray and immunohistochemistry: VEGFR-3, HER2, CD44v6, CXCR4, TIMP-1, EGFR, IGF-1R, IGF-2, IGFBP-1, ECAD, MMP-9, RKIP, CD133, MSI. Chi-squared test and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis.</p><p><b>RESULTS</b>The positive expression rates of biomarkers were as following: VEGFR-3 (44.3%), EGFR (30.5%), HER-2 (28.1%), IGF-1R (63.5%), IGF-2 (44.8%), IGFBP-1 (70.9%), ECAD (45.8%), CD44v6 (51.2%), MMP-9 (44.3%), TIMP-1 (41.4%), RKIP (45.3%), CXCR4 (40.9%), and CD133 (49.8%). The positive rate of MSI expression was 22.2%. Both univariate and multivariate analyses showed that VEGFR-3, HER-2, and TIMP-1 were significant predictors of lymph node metastasis. Univariate analysis showed that CD44v6 and CXCR4 were significant significant predictors of lymph node metastasis.</p><p><b>CONCLUSIONS</b>VEGFR-3, HER2 and TIMP-1 are independent factors for lymph node metastasis in stage T1 and T2 colorectal cancers.</p>

Comparative study on endoscopic thyroidectomy versus conventional thyroidectomy in thyroid disease / 中国基层医药

ObjectiveThe aim of this study was to evaluate and compare the surgical outcomes of endoscop ic and conventional open thyroidectomies in patients with thyroid disease.Methods116 patients with tyroid tumor were enrolled.56 patients underwent endoscopic thyroidectomy ( endoscopic group ),and 60 patients underwent conventional open thyroidectomy( conventional group).We analyzed the patients' clinic characteristics,surgical outcomes and complications between the two groups.ResultsThe blood loss was less in the endoscopic group than the open group[( 16.8 ± 9.6) ml vs ( 24.9 ± 14.2 ) ml,t =- 2.427,P ＜ 0.05].The degree of satisfaction for cosmetic outcome in endoscopy group( 96.4％ ) was higher than that in conventional group ( 16.7％ ) ( x2 =74.508,P ＜ 0.01 ).There was no significant difference in the operating time,volume of drainage and postoperative hospital stay between two groups,and there was no significant difference in the skin ecchymosis,redness and swelling and postoperative pain between two groups( all P ＞ 0.05).No severe postoperative complication was encountered,such as injuries of the re current or superior laryngeal nerve,parathyroid gland injury or massive hemorrhage.ConclusionEndoscopic thyroidectomy has less blood loss,mini-open and excellent cosmetic benefits compared with conventional open thyroidectomy.

Surgical treatment for 140 patients with gastric stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To analyze the outcome of the patients with gastric gastrointestinal stromal tumor(GIST) after surgical treatment and identify the associated risk factors.</p><p><b>METHODS</b>Clinical data and the tissue slices including immunohistochemistry staining of 140 patients with gastric GIST from January 1990 to December 2008 were retrospectively reviewed. SPSS 16.0 for Windows software package was used for statistical analysis.</p><p><b>RESULTS</b>The overall survival rates of 1-, 3-, 5-year were 96.8%, 86.7% and 79.3%, respectively. The survival rates of 1-, 3-, 5-year were 98.1%, 90.0% and 85.4% in patients who underwent complete tumor resection. But the survival rates of 1-, 3-, 5-year were 38.1%, 0 and 0 in patients with incomplete tumor resection. The differences were statistically significant (P<0.05). Gender, preoperative metastasis, tumor size,pathology type,karyokinesis, recurrence and metastasis were associated with survival rates in patients with complete tumor resection by univariate analysis. However, only tumor size, karyokinesis, recurrence and metastasis were associated with survival rates by Cox regression multivariable analysis(P<0.05).</p><p><b>CONCLUSION</b>Surgery remains the main treatment for gastric GIST. Local complete resection is the principal treatment.</p>

Selective cytotoxic effect of lentivirus-mediated double suicide gene transfer on human gastric adneocarcinoma cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the selective cytotoxic effect of lentivirus-mediated double suicide gene (CD/TK) against human gastric carcinoma cells SGC-7901 in vitro.</p><p><b>METHODS</b>SGC-7901 cells were infected with FGW-KDRP-CD/TK vector and the infection efficiency was observed under a fluorescence microscope. The morphological changes of the infected cells were observed by Giemsa staining. Flow cytometry (FCM) was employed for cell cycle analysis, and the expression of CD/TK was detected by RT-PCR. The infected cells were then treated with the prodrugs ganciclovir (GCV) and/or 5-fluorocytosine (5-FC) at different concentrations, and the cytotoxic effects were evaluated using MTT method.</p><p><b>RESULTS</b>The infection efficiency of the lentiviral vector in SGC-7901 cells increased with the titer of the virus, which produced no significant effect on the cancer cell morphology in vitro or on the percentages of G0-G1, G2-M and S phase cells (P>0.05). RT-PCR demonstrated the expression of CD/TK gene in SGC-7901 cells infected by FGW-KDRP-CD/TK. The infected cells were highly sensitive to the prodrugs with a dose-dependent cytotoxic effect within a specific concentration range of the drugs, whereas the non-infected cells were not sensitive to the prodrugs. Combined use of the two prodrugs produced an obviously stronger inhibitory effect than either of the them (P<0.05). When combined, GCV and 5-FC at the concentration of 0.1+40, 1+80, 10+160, and 100+320 mg/L demonstrated a synergetic effect with a CDI<1.</p><p><b>CONCLUSION</b>Lentivirus-mediated CD/TK fusion gene system can selectively kill gastric cancer cells, and the two prodrugs show a synergistic cytotoxic effect.</p>

Targeting therapy for colorectal cancer with double suicide genes driven by VEGF promoter / 中华普通外科杂志

Objective To investigate the curative effect of an adenovirus-mediated fusion gene system driven by VEGF promoter (AdVEGF-CDglyTK) on a nude mouse model of colorectal cancer and analyze the mechanism underlying its therapeutic effect.Methods The animal model of the colorectal cancer was established by using transplantation of the cultivated cells,human colorectal cell line LoVo,via subcutaneous injection on the back of nude mice.Twenty nude mice were equally divided into four groups:group Ⅰ received injection of AdVEGF-CDgiyTK plus 5-flurocytosine/ganciclovir(5-FC/GCV);group Ⅱwere given 5-FC/GCV;group Ⅲ were with AdVEGF-CDglyTK;group Ⅳ were used as control.Results CDglyTK was expressed exclusively in the tumor tissues from the group Ⅰ and Ⅲ by RT-PCR.The phenotype and pathological analysis showed that tumor growth was dramatically inhibited in group Ⅰwhen compared with other three groups,while no significant difference was found between group Ⅱ,group Ⅲ and group Ⅳ.The TUNEL assay demonstrated that the apoptosis rate of 38.65% ± 4.20 significantly increased in group Ⅰ when compared with other three groups (F = 397.530,P =0.000).The tumor microvessel density of 3.08±0.79 decreased significantly in group Ⅰ (F = 34.081,P = 0.000) when compared with other three groups.Conclusion The results suggested that AdVEGF-CDglyTK with 5-FC/GCV can inhibit the tumor growth of colorectal cancer significantly in vivo by a mechanism of systeminduced apoptosis and the efficient suppression of angiogenesis.

A double suicide gene system driven by KDR promoter selectively kills human hepatic carcinoma cells and human umbilical vein endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the selective killing effects of adenovirus (Ad)-mediated double suicide gene system driven by KDR promoter (KDR-CdglyTK) on the human hepatic carcinoma cells and human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>KDR-expressing BEL-7402 and HUVECs and HepG2 cells that did not express KDR were infected by KDR-CdglyTK, and the infection efficiency and the expression of CdglyTK in the cells was detected by RT-PCR. The infected cells were treated with the the prodrugs 5-FC and GCV at different concentrations, and the cell-killing effects and bystander effects were evaluated by MTT method.</p><p><b>RESULTS</b>At the multiplicity of infection (MOI) of 100, the recombinant AdKDR-CDglyTK showed similar infection efficiency in the 3 cell lines. RT-PCR demonstrated CDglyTK expression in the recombinant adenovirus and the 3 infected cell lines. BEL-7402 and HUVECs infected by the KDR-CdglyTK, but not the HepG2 cells, were highly sensitive to the prodrugs (P<0.001). Bystander effects of the double suicide gene system were observed in the coculture of the infected and non-infected BEL-7402 and HUVECs.</p><p><b>CONCLUSION</b>The double suicide gene system driven by KDR promoter has specific killing effect on KDR-expressing hepatocellular carcinoma cells and HUVECs.</p>

Adenovirus-mediated double suicide gene selectively kills breast cancer MCF-7 cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of adenovirus-mediated double suicide gene (CD/TK) for selective killing of breast cancer cells.</p><p><b>METHODS</b>Vascular endothelial growth factor (VEGF)-expressing MCF-7 cells and normal human mammary epithelial cells that did not express VEGF were infected with the adenovirus containing VEGFP-CD/TK-GFP genes. CD/TK gene expression in the infected cells was detected by RT-PCR. After treatment of the infected cells with GCV and/or 5-FC, the cell growth status was evaluated using MTT assay, and the cell cycle changes were detected with flow cytometry. In nude mice bearing human breast cancer, the recombinant adenovirus vector was injected directly into the tumor followed by intraperitoneal injection of the prodrugs GCV and/or 5-FC, and the subsequent tumor growth was observed.</p><p><b>RESULTS</b>The recombinant adenovirus achieved similar infection rates in MCF-7 and human mammary epithelial cells, and the rates increased gradually with the multiplicity of infection (MOI) of the virus. RT-PCR demonstrated the presence of CD/TK gene product in infected MCF-7 cells, but not in the infected mammary epithelial cells. The infected MCF-7 cells, but not the mammary epithelial cells, were highly sensitive to the pro-drugs. The CD/TK fusion gene system showed significantly greater efficiency than either of the single suicide gene in killing the target cells (P<0.01). At the MOI of 100, treatment of the infected cells with the pro-drugs resulted in increased cell percentage in G(0)-G(1) phase and decreased percentage in S phase. In nude mice bearing MCF-7 cell-derived subcutaneous tumor, treatment with the double suicide gene system significantly inhibited the tumor growth, showing much stronger effect than either of the single suicide gene (P<0.01).</p><p><b>CONCLUSION</b>The adenovirus-mediated CD/TK double suicide gene driven by VEGF promoter combined with GCV and 5-FC treatment can be an effective therapy against experimental breast cancer, and produces much greater efficacy than the single suicide gene CD/TK combined with GCV or 5-FC.</p>

Adenovirus mediated fusion gene system driven by VEGF promoter kills pancreatic cancer cell / 中华普通外科杂志

Objective To evaluate the selectively killing effect of adenovirus(Ad)mediated double suicide gene driven by VEGF promoter on pancreatic cancer cell SW1990. Methods VEGFexpressing SW1990 were infected by Ad-VEGFP-CDTK and Ad-null.respectively.The infection rate was observed and the expression of CDTK was detected by RT-PCR and Western blotting.Followed by treatment with 5-FC and GCV killing effects were evaluated and bystander effects were analyzed by MTF.Pathological character of cells was observed by electron microscopy and distribution of cell cycle was detected by flow cytometry.The caspase-3 activity was detected by absorption spectrometry. Results The infection rate of the resultant recombinant Ad to SW1990 cells was not apparently different.RT-PCR and Western blotting demonstrated product of CDTK gene in SW1990 cell infected by Ad-VEGFP-CDTK.Prodrug could inhibit proliferation of SW1990 and the effect was dose-dependent.There was considerable bystander effect as observed by MTF.Apoptotic peak was also shown by flow cytometry.Morphologic features of apoptosis in SW1990 cells were displayed via electron microscopy.Cells at the G0-G1 phase was increasing and the rate at the G2-M and S phase was decreased by prodrug.The caspase-3 activity gradually rised with the increasing concentration of the prodrug. Conclusions The CDTK fusion gene system controlled by VEGF promoter has killing effect on the VEGF-expressing SW1990 cells and inducing the cell apoptosis.

Surgical treatment for gastrointestinal stromal tumor / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the effects of surgical treatment for gastrointestinal stromal tumors (GISTs) and influential factors of survival.</p><p><b>METHODS</b>The clinical data and the tissue slices including immunohistochemical staining of 153 cases of GISTs from January 1990 to March 2006 were rechecked retrospectively. All patients were followed up carefully. More attention was paid to the surgical effects and the influential factors of survival.</p><p><b>RESULTS</b>The overall survival rates at 1-, 2-, 3-, 4- and 5-year were 94.9%, 83.3%, 73.3%, 70.5% and 64.3%, respectively. The median survival time for patients with tumor resected completely was 66.0 months, and the 2- and 5-year survival rate were 89.4% and 70.9% respectively. The median survival time was 23.8 months for the patients with tumor resected partly, and only two of these patients survived over 2 years. Gender, tumor sites, preoperative metastasis, tumor size, pathological type, karyokinesis and recurrence and metastasis were related with survival rates for the patients with tumor resected completely on univariate analysis, but tumor size, pathology type, recurrence and metastasis were related with survival rates on Cox regression multivariate analysis (P < 0.05).</p><p><b>CONCLUSIONS</b>Surgery should still be the main therapy for GISTs. Local complete resection is the principal treatment. The survival cannot be improved by extensive resection and lymph nodes clearance.</p>

Specific killing effects of double suicide gene system on pancreatic cancer Capan-2 cells / 肿瘤

Objective: To evaluate the specific killing effect of adenovirus (Ad)-mediated double suicide gene system (CD/TK fusion genes) driven by VEGF promoter on pancreatic cancer Capan-2 cells. Methods: VEGF-positive Capan-2 cells were transfected with Ad-VEGFP-CDTK. Ad-free vector acted as negative control. The transfection efficiency was observed and the transcription of CDTK gene was detected by RT-PCR. The Capan-2 cells were treated with 5-fluorocytosine (5-FC) and ganciclovir (GCV) at different concentrations. The effects of the double suicide gene system on cell proliferation and the bystander effects were assessed by MTT assay. Then morphological changes were observed by electronic microscopy and distribution of cell cycle was determined by flow cytometry. Human pancreatic cancer Capan-2 cells were subcutaneously implanted into nude mice. The tumor inhibition rate was calculated. Results: The infection rates of the two resultant recombinant Ads in Capan-2 cells were not significantly different, and they were gradually elevated with the increase in multiple of infection (MOI) of Ads. MTT assay showed that pre-drug dose-dependently inhibited the growth of Capan-2 cells. Apparent bystander effects were also observed. Electronic microscopy demonstrated apoptotic changes of Capan-2 cells. Typical apoptotic peak was detected in double suicide gene system-treated group by flow cytometry. Cell cycle distribution analysis showed that the proportion of G0/G1 increased and the number of cells in G2/M and S phase decreased after treatment. The implanted tumor model was successfully established in nude mice. The tumor size was decreased significantly after treatment with double suicide gene system. Conclusion: The promoter of VEGF regulated double suicide gene system can specifically kill pancreatic cancer Capan-2 cells and induce apoptosis in vitro. And it significantly inhibites the growth of implanted pancreatic tumor in nude mice.

Preliminary effect of VEGF promoter-driven recombinant adenovirus containing double suicide genes on apoptosis of human gastric carcinoma cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of the adenovirus containing CD/TK fusion gene controlled by the human vascular endothelial growth factor (VEGF) promoter on apoptosis of human gastric carcinoma cells SGC-7901.</p><p><b>METHODS</b>VEGF-expressing SGC-7901 cells were infected by the recombinant adenovirus Ad-VEGFP-CD/TK, and the infection efficiencies were observed with fluorescence microscopy. The toxic effect and intracellular calcium concentration induced by 5-fluorocytosine (5-FC) and ganciclovic (GCV) were determined by light microscopy, electron microscopy and flow cytometry.</p><p><b>RESULTS</b>The transfection efficiency of the recombinant adenovirus in SGC-7901 cells increased with the viral titer. At the multiplicity of infection (MOI) of 100, 5-FC and GCV could induce apoptosis of SGC-7901 cells within a given dose range in a dose- and time-dependent manner, and apoptotic changes of the cells were observed with electron microscopy. Apoptotic peak was also detected by flow cytometry. Cell cycle analysis revealed increased cell percentage in G(0)-G(1) phase and decreased percentage of cells in G(2)-M and S phases in response to treatment with the pro-drugs, which also induced marked elevation of intracellular calcium concentration in the infected cells.</p><p><b>CONCLUSIONS</b>CD/TK fusion gene system driven by VECF promoter selectively induces apoptosis of VEGF-expressing SGC-7901 cells, the action of which is probably mediated by intracellular calcium variation.</p>

Experimental studies on apoptosis of human hepatocellular carcinoma cell induced by VEGFP-CDglyTK system / 解放军医学杂志

Objective To study the effects of suicide gene system mediated by adenovirus containing the CD-TK fusion gene controlled by human vascular endothelial growth factor(VEGF)promoter on apoptosis of human hepatocellular carcinoma cells HepG2 in vitro.Methods The VEGF-expressing HepG2 cells were infected by adenovirus vector containing CD-TK fusion gene controlled by the VEGF promoter(Ad-VEGFP-CDglyTK).The infection efficiencies in HepG2 cells were observed under a fluorescence microscope.The toxic effect of 5-fluorocytosine(5-FC)and ganciclovic(GCV)on infected cells was determined by light microscopy,electron-microscopy and flow cytometry(FCM).Results The transfection efficiency in HepG2 cells increased with the increasing adenoviral titer.The pro-drug(5-FC and GCV)could induce apoptosis of HepG2 cells in certain range of dosage(the doses of GCV+5-FC:1mg/L + 20mg/L,10mg/L + 40mg/L,100mg/L + 60mg/L)at the multiplicity of infection(MOI)of 100.The effect showed a time-dependent manner.HepG2 cells showed typical morphologic changes of apoptosis after administration of the pro-drug(GCV:10mg/L,5-FC:40mg/L)for 72 hours:chromatin condensation and disposition along nuclear membrane.Karyopyknosis and karyoklasis were seen under electron microscopy(?10 000).Apoptotic peak was also shown in HepG2 cells treated with the pro-drug(5-FC and GCV)by flow cytometry.The cell apoptosis rate was increased accordingly as the concentration of pro-drug(5-FC and GCV)increased.The apoptosis was increased obviously in comparison with the negative control group(P