AIM: To investigate the ocular complication after radiation therapy for nasopharyngeal carcinoma(NPC).METHODS: The authors performed a previous study on keratopathy in 213 NPC patients who received first stage radiation and had at least 10 months of follow-up. These patients were categorized into three groups depending on NPC clinic stages. Rates and proportions of keratopathy occurring in these groups were compared and analyzed with Chi-square Test and Spearman rank correlation coefficient.RESULTS: Radiation keratopathy developed in 19 patients, about 8.9% (19/213). The latency value was 3 to 30days. The effect of NPC clinic stages and radiation did on the development of keratopathy was not statistically significant (P＞0.05).CONCLUSION: The NPC clinic stages and radiation doses plays few effects on the development of keratopathy. It may play a key role that corneal nerves damage induced ocular surface diseases. It can not be excluded that individuals have different sensitivities to radiation.

OBJECTIVE: To assess the influence of apolipoprotein E (ApoE) gene polymorphisms on the therapeutic effect of lipid-lowering statins in patients with ischemic cerebral infarction. METHODS: One hundred and six patients with ischemic cerebral infarction who orally took lipid-lowering statins for 3 months were enrolled. Changes in serum triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) before and after the drug administration were analyzed. ApoE gene polymorphisms were detected by real-time fluorescent quantitative PCR, and genotypes of ApoE gene in patients with different effects were compared. RESULTS: The detection rates for E2/E2, E2/E3, E3/E3, E2/E4 and E3/E4 genotypes were 0.94%, 11.32%, 63.21%, 1.89% and 22.64%, respectively. And the detection rates for E2, E3 and E4 alleles were 7.55%, 80.19% and 12.26%, respectively. Biochemical phenotypes included E2 type (13 cases, 12.26%), E3 type (69 cases, 65.09%) and E4 type (24 cases, 22.65%). Before administration, TG and TC of E2 type were the highest (P<0.05), but no significant difference was detected in HDL-C and LDL-C among the three phenotypes (P>0.05).Following the drug administration, TG, TC and LDL-C were decreased, while HDL-C was increased. HDL-C of E2 type was the highest, TC and LDL-C of E4 type were the highest (P<0.05). The E3/E3 ratio in low-efficiency group at admission was lower than that in the high-efficiency group, while the E3/E4 ratio was higher than that in the high-efficiency group (P<0.05). The proportion of E3 allele in low-efficiency group was lower than that in high-efficiency group, while the proportion of E4 allele was higher than that in high-efficiency group (P<0.05). CONCLUSION ApoE gene polymorphisms are closely correlated with the therapeutic effect of lipid-lowering statins in patients with ischemic cerebral infarction. The lipid-lowering effects are more significant in patients with E2 and E3 genotypes, but were poor in those with the E4 genotype. Personalized regimens should be applied.
Apolipoproteins E/genetics* ; Cerebral Infarction/genetics* ; Genotype ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Lipids ; Polymorphism, Genetic ; Triglycerides

Objective To observe the diagnostic value of non-invasive 128-slice computed tomography coronary angiography(CTA)in comparison with invasive coronary angiography.Methods 128-slice CTA and invasive coronary angiography were performed in 78 unselected consecutive patients(63 patients with suspected coronary artery disease and 15 patients with previous coronary stenting,56 males,mean age 61±10 years)and ＞50% reduction of minimal lumen diameter was defined as significant coronary stenosis.Results Fifty-eight out of 879 segments(7%)from CTA were not assessable because of irreguldr rhythm,vessel calcification or tachycardia.Compared with invasive coronary angiography,segmentbased analysis from the 821 segments showed the sensitivity by CTA was 87%,specificity 97%,PPV 83% and NPV 97%.Four out of 22 stents implanted in 15 patients were not assessable by CTA because of poor image quality.Compared with invasive coronary angiography,the sensitivity of diagnosing in-stent restenosis by CTA was 100%,specificity 77%,PPV 63% and NPV 100% for the remaining 18 stents-Conclusions One hundred and twenty-eight-slice CTA has a high accuracy for detecting coronary artery disease and instent restenosis after coronary stenting and could be considered as a valuable noninvasive technique for screening coronary artery disease in suspected patients.

This study was purpose to establish the transgenic mouse models of the truncated platelet integrin β3 by retrovirus-infected hematopoietic stem cells (HSCs) transplantation and to provide the basis for further study of the role of integrin β3 cytoplasmic domain in platelet bi-directional signaling pathways. Wild-type β3, β3-Δ759 (R(760) GT(762) truncated β3) and β3-Δ754 (T(755) NITYRGT(762) truncated β3) cDNAs were subcloned into MSCV MigR1 retroviral vector bearing a GFP gene and packaged into infective retrovirus with BOSC23 cell strain. The bone marrow HSCs of the β3 deficient mice were infected by the retroviruses, and transplanted into lethally-irradiated wild type C57BL/6 mice. GFP positive rate and surface β3 expression of the recipients' platelets at 6 to 8 weeks after transplantation were detected by flow cytometry to evaluate the transgenic efficiency. The results showed that four kinds of transgenic mouse models including vector, wild-type β3, β3-Δ759 and β3-Δ754 were established successfully. GFP positive rates of transgenic mouse platelets ranged from 18% to 66% and the β3 expression of transgenic mouse reached heterozygote (β3(+/-) level of mouse). It is concluded that establishment of transgenic mouse models mediated by retrovirus-infected HSCs transplantation is a feasible, fast, and high throughput transgenic approach and laid a solid foundation for further research on the role of integrin β3 cytoplasmic domain for bi-directional signaling of platelets in vivo, and for the gene therapy of platelet disorders.
Animals ; Blood Platelets ; metabolism ; Genetic Vectors ; Hematopoietic Stem Cell Transplantation ; Integrin beta3 ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Retroviridae ; genetics

OBJECTIVETo compare the effects of doxycycline, losartan, and their combination in the prevention of left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats.

METHODSTwenty-four hours after the induction of AMI, the 254 survival rats were randomly assigned to the following groups and received drug treatment: (1) AMI controls (n=64), (2) doxycycline (30 mg x kg(-1) x d(-1), n = 63), (3) losartan (10 mg x kg(-1) x d(-1), n = 62), and (4) combination doxycycline and losartan (30 and 10 mg x kg(-1) x d(-1) respectively, n = 65) treatment groups. Also, sham operated rats (n = 30) were selected randomly. Each group was further divided into three subgroups of 1, 2, and 4 weeks of treatment. After the completion of treatment, hemodynamic studies were performed. Then, the heart of rat was fixed and analyzed pathologically.

RESULTSExclusive of the dead rats and the hearts with the myocardial infarction size < 35% or > 50%, complete experimental data were obtained in 157 rats. Besides sham operated rats, there was no significant difference in myocardial infarction sizes among the 12 subgroups of AMI control and drug treatment groups (P> 0.05). Compared with sham operated rats, left ventricular end diastolic pressure (LVEDP) and left ventricular absolute weight and relative weight (LVAW and LVRW) were significantly increased in 1, 2, and 4 week subgroups of AMI controls (P < 0.05, P < 0.01, and P < 0.001, respectively), with LVEDP elevated more significantly in 4 week than in 1 and 2 week subgroups (P < 0.01); whereas the maximum rising and dropping rate of left ventricular pressure (+/-dp/dt) and its corrected value by left ventricular systolic pressure (+/-dp/dt/LVSP) were all significantly decreased only at 4 week subgroup of AMI controls (P < 0.001). Compared with AMI controls group, LVEDP was significantly decreased in all 1, 2, and 4 week subgroups of the three treatment groups (P < 0.05, P < 0.01, and P < 0.001, respectively); LVAW and LVRW were significantly decreased in 2 and 4 week subgroups of losartan and combination groups (P < 0.05, P < 0.01, P < 0.001, respectively), and in only 4 week subgroup in doxycycline (P < 0.05, P < 0.01, and P < 0.001, respectively); whereas the maximum dropping rate of left ventricular pressure and the corrected value of left ventricular pressure rising and dropping rate were significantly increased only in 4 week subgroups of all three treatment groups (P < 0.05, P < 0.01, respectively). There is no significant difference in all indices above among the three treatment groups at all three time points (P > 0.05).

CONCLUSIONIt is indicated that doxycycline can prevent left ventricular remodeling and improve its systolic and diastolic function after AMI in rats, with the equivalent effect to that of losartan. There seems no additive effect when the two drugs are used in combination.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Doxycycline ; therapeutic use ; Female ; Losartan ; therapeutic use ; Myocardial Infarction ; drug therapy ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ventricular Remodeling ; drug effects

OBJECTIVETo study the incidence and risk factors of HIV and syphilis seroconversion among men who have sex with men (MSM) in Beijing.

METHODSA total of 550 MSM were recruited on the basis of community and followed up after 6 and 12 months in Beijing. Each subject was investigated by only one investigator at one time to collect information on demographics and behaviors. Blood samples were collected to test HIV and syphilis seroconversion. ELISA was used for screening test, west blotting (WB) and Particle agglutination were used for confirmatory test.

RESULTSA total of 550 MSM investigated, among which 4.5% (25/550) were HIV-positive and 29.3% (161/550) were syphilis-positive. For 525 HIV-negative MSM, 87.0% (457/525) retained during the 12-month investigation. Seroincidence for HIV and syphilis were 3.37/100 person-years (95%CI = 1.66 - 5.08) and 9.32/100 person-years (95%CI = 5.87 - 12.77) respectively. HIV seroconversions for those who performed and did not perform rectal douching after homosexual anal intercourse in the past 3 months were 7.11/100 and 0.76/100 person-years respectively. Multivariate Cox regression analysis revealed that rectal douching after homosexual anal intercourse in the past 3 months (HR = 9.23, 95%CI = 2.08 - 40.88) was significantly associated with HIV seroconversion. Syphilis seroconversions for those who met male sex partners in parks, public washrooms or bathhouses in the past 3 months were 41.77/100 and 7.97/100 person-years respectively. Syphilis seroconversions for those who performed and did not perform rectal douching after homosexual anal intercourse in the past 3 months were 16.17/100 and 4.92/100 person-years respectively. In the past 3 months, meeting male sex partners in parks, public washrooms or bathhouses (HR = 4.67, 95%CI = 1.77 - 12.34) and performing rectal douching after homosexual anal intercourse (HR = 3.09, 95%CI = 1.40 - 6.83) were significantly associated with syphilis seroconversion.

CONCLUSIONThe seroconversions of HIV and syphilis during the follow-up visits in this MSM cohort study in Beijing were very serious, and that the associated factors for seroconversions were rectal douching after homosexual anal intercourse and meeting male sex partners in parks, public washrooms or bathhouses.

Adolescent ; Adult ; Antibodies, Bacterial ; blood ; China ; epidemiology ; HIV ; immunology ; HIV Antibodies ; blood ; HIV Infections ; blood ; epidemiology ; HIV Seropositivity ; blood ; epidemiology ; Homosexuality, Male ; Humans ; Incidence ; Male ; Risk Factors ; Sexual Behavior ; Syphilis ; blood ; epidemiology ; Treponema pallidum ; immunology ; Young Adult

OBJECTIVETo compare the effects of matrix metalloproteinase (MMP) inhibitor doxycycline, losartan, and their combination on the expression of MMP-8, 13, tissue inhibitor of MMP-1, 2 (TIMP-1, 2), and collagen remodeling in the noninfarcted myocardium after acute myocardial infarction (AMI) in rats.

METHODSTwo hundred and fifty-four AMI rats, induced by left coronary ligation, were randomly assigned to the following groups: (1) AMI controls group (n = 64); (2) doxycycline group (30 mg x kg(-1) x d(-1), n = 63); (3) losartan group (10 mg x kg(-1) x d(-1), n = 62); (4) concomitant doxycycline and losartan group (30 and 10 mg x kg(-1) x d(-1) respectively, n = 65); and (5) Sham-operated rats (n = 30), which were randomly selected to serve as noninfarction controls. Each group was further divided into three subgroups of 1, 2, and 4 weeks that received treatment. After the completion of treatment, the rats were killed. The mRNA and protein expression of MMPs and TIMPs in the noninfarcted myocardium were quantified by RT-PCR and Western blot, respectively. The type I and type III collagen volume fraction (CVF) of the noninfarced myocardium were assessed immunohistochemically.

RESULTSNo significant difference existed in myocardial infarction sizes among the 12 subgroups of AMI controls and the three treatment groups (42%-48%, all P > 0.05). Compared with sham operated rats, the mRNA and protein expression of MMP-8 and 13 significantly increased by 39%-183% in all three subgroups of AMI controls (all P < 0.05), except both of their mRNA expressions in 2-week subgroups; the mRNA and protein levels of TIMP-1 increased only in 1-week subgroup of AMI controls by 104% and 67%, respectively (both P < 0.05); the mRNA of TIMP-2 increased in all 1, 2, and 4-week subgroups by 144%-232% (all P < 0.05), but its protein expression lagged and only enhanced in 2 and 4-week subgroups of AMI controls by 231% and 332%, respectively (both P < 0.05). Meanwhile, both type I and type III CVF of noninfarcted myocardium significantly increased in all three subgroups of AMI controls (type I CVF: 3.01%-5.64% vs 1.53%-1.67%, P < 0.01-0.001; type III CVF: 2.19%-4.42% vs 1.46%-1.59%, P < 0.05-0.001), with type I CVF being higher in 4-week than in 1 and 2-week subgroups (5.64% vs 3.01% and 3.02% respectively, all P < 0.05). Compared with AMI controls, all three kinds of treatment significantly reduced the increased mRNA and protein expressions of MMP-8, 13 and TIMP-1, 2 after AMI by 14%-60% (all P < 0.05), as well as type I/III CVF in their 2 and 4-week subgroups (type I CVF: 1.56%-2.38% vs 3.02%-5.64%, P < 0.05-0.001; type III CVF: 1.92%-2.65% vs 4.19%-4.42%, P < 0.05-0.01), except for doxycycline's effect on type III CVF in any of its three subgroups (all P > 0.05). Among the three treatment groups, significant differences existed in the above mentioned indicators only at some subgroup levels (all P < 0.05).

CONCLUSIONSLike losartan, doxycycline can also suppress the enhanced mRNA and protein expression of MMP-8, 13 and TIMP-1, 2, and reduce type I collagen deposition in the noninfarcted myocardium after AMI in rats. However, it has no effect on type III collagen deposition.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Animals ; Collagen Type I ; biosynthesis ; genetics ; Collagenases ; biosynthesis ; genetics ; Doxycycline ; pharmacology ; Drug Synergism ; Female ; Losartan ; pharmacology ; Matrix Metalloproteinase 13 ; Matrix Metalloproteinase 8 ; biosynthesis ; genetics ; Matrix Metalloproteinase Inhibitors ; Myocardial Infarction ; metabolism ; Myocardium ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics ; Tissue Inhibitor of Metalloproteinase-2 ; biosynthesis ; genetics ; Tissue Inhibitor of Metalloproteinases ; biosynthesis ; genetics

OBJECTIVETo study the effect of dimethoate on the monoamine Neurotransmitters, including norepinephrine (NE), epinephrine (E), serotonin (5-HT), dopamine (DA) and its metabolite (3, 4-hydroxyphenylacetic acid, DOPAC) in the serum of rats and furthermore to explore the non-cholinergic mechanism of organophosphate induced toxicity.

METHODSGroups of rats were treated with saline and 38.9, 83.7 and 180 mg/kg dimethoate respectively and were decapitated at the different time course from 0.5 to 24 hours after the administration. The monoamines neurotransmitters were determined by the reverse-phase high-performance liquid chromatography with the electrochemical detection.

RESULTSThe serum concentrations of DA (8.42% - 248.42% of the control), DOPAC (17.22% - 68.21% of the control) increased, according with the DM dosage and the exposure time, while the levels of NE (9.65% - 38.26% of the control) and E (11.00% - 32.62% of the control) contents decreased at the same time.

CONCLUSIONThese findings indicate that dimethoate induced toxic effects can alter the monoamine levels at the different dosage and the time exposure in the serum of rats. It suggests that some non-cholinergic mechanisms may be involved in the dimethoate intoxication.

3,4-Dihydroxyphenylacetic Acid ; blood ; Animals ; Biogenic Monoamines ; blood ; Dimethoate ; toxicity ; Dopamine ; blood ; Dose-Response Relationship, Drug ; Epinephrine ; blood ; Male ; Norepinephrine ; blood ; Rats ; Rats, Sprague-Dawley ; Serotonin ; blood

Objective To investigated the effects of interleukin -1β( IL-1β) on the intracellular cholesterol contents of HepG 2 cells treated by compactin.Methods HepG2 cells were treated with different con-centrations of compactin (0, 1, 10, 50, 100 μmol· L-1 ) in the absence or presence of 20 ng· mL-1 IL-1βfor 24 hours.Commercial kits was used to evaluated the enzymatic activity of 3-hydroxy-3-methyl-glu-taryl (HMG) -CoA reductase ( HMG-CoA -R).Real -time PCR was used to determine the mRNA of low density lipoprotein ( LDL) rece-puter.Then HepG2 cells treated with 100 μmol · L-1 compactin in the absence or presence of 20 ng· mL-1 IL-1βwere chose to evaluated the content of intracellular cholesterol by commercial kits , real -time PCR was used to determine the mRNA of acyl coenzyme A -cholesterol acyl-transferase ( ACAT ).Results Compactin dose dependently reduced HMG-CoA -R enzymatic activity.IL -1βupregulated the enymatic activity of HMG-CoA reductase , LDL receptor , and the expression of acyl -coenzyme A -cholesterol acyltransferase mRNA , which was accompanied with increased intracellular cholesterol ester contents. Conclusion Inflammatory cytokine disrupted the suppressive effect of compactin on the HMG -CoA-R enzymatic ac-tivity in HepG2 cells and increased the expression of ACAT and LDL receptor and may contribute to hepatic cholesterol accumulation under inflammatory conditions.

Objective To investigate the effect of atorvastatin on oxidative stress and intracellular lipid accumulation in HepG2 cells under inflammatory state and explore the underlying mechanism.Methods HepG2 cells were treated with 100 ng · mL-1 TNF-α,100 ng · mL-1 TNF-α ± 10 μmol · L-1 atorvastatin in the presence of LDL for 24 h.Oil red O staining was used to examine the intracellular lipid contents.The mRNA and protein expressions of lipogenic genes (FAS,ACC and SREBP1) were detected by real-time polymerase chain reaction and Western blot.ROS levels were measured with the fluorescent probe of DCFH-DA.Contents of H2O2 and MDA were determined using the colorimetric method.Results Compared with normal group(the gray value of SREBP1 was 1.01 ± 0.001),the gray value of SREBP1 in model group was 1.61 ± 0.34.The mRNA levels in normal group of SREBP1,FAS,ACC respectively were 1.01 ± 0.16,1.03 ± 0.32,0.95 ± 0.29,the values in model group respectively were 3.61 ± 0.39,1.99 ± 0.36,2.37 ± 0.52,the differences were statistically significantly (P ＜ 0.05).Compared with model group,the mRNA levels of SREBP1,FAS,ACC and the gray value of SREBP1 in experimental group respectively were 2.95 ± 0.92,3.99 ± 1.16,2.85 ± 0.91,2.94 ± 0.65,the differences were statistically significantly(P ＜0.05).At the same time,compared with normal group,the levels of ROS(fluorescenceintensity),H2O2,MDA respectively were 1.00 ±0.20,and (2.30 ±0.31) (0.78 ±0.22) nmol · mg-1,the levels in model group respectively were 1.77 ± 0.25 and (4.32 ± 0.77),(1.86 ± 0.23) nmol · mg-1,the differences were statistically significantly (P ＜ 0.05).Compared with model group,the levels of ROS,H2 O2,MDA in HepG2 cells in experimental group respectively were 3.2 ±0.53 and (5.31 ±0.75),(3.43 ± 1.15) nmol · mg-1,the differences were statistically significantly(P ＜ 0.05).Conclusion Atorvastatin induced intracellular lipid accumulation in HepG2 cells under inflammatory stress,which may be associated with the increased oxidative stress.