Objective To explore the correlation between the ultrasonographic parameters describing the tumor and proliferative activity, invasiveness of the rabbit renal VX 2 tumor. Methods Animal models were established in 56 rabbits,in which left kidneys were transplanted with VX 2 tumor. The second harmonic imaging and video-density quantitative determination were applied to observe the size, echo-intensity and edge echo-pattern of the rabbit renal VX 2 tumor. The findings were compared with those of histopathologic section and DNA analysis calculated with the flow cytometer. Results The number of tumor cell with higher proliferative index(PI) and ploidy cell rate(PCR) increased with the tumor size. The tumors of hyperecho and more blood flow with obvious necrosis tissue, fibrotic lesion and blood sinusoid got higher PI and PCR than the tumors of hypoecho and less blood flow, while there was no statistic significant correlation between the echoic patterns of the tumor edge and DNA analysis.Conclusions The ultrasonographic parameters describing the tumor, such as the size, echo-intensity and blood flow, can be used to evaluate the proliferative activity and invasiveness of the renal tumor.

Animal Feed ; Animals ; Ascorbic Acid ; pharmacology ; Cadmium ; analysis ; DNA ; analysis ; Hepatocytes ; chemistry ; Rats ; Rats, Wistar ; Selenium ; analysis

Objective Post-transcription RNA interference (RNAi) is more and more widely applied in multigene therapy.This study aimed to establish an subcutaneous xenotransplanted tumor (SXT) model of human HT-29 colon carcinoma in nude mice and investigate the effects of the survivin shRNA-APC double gene co-expression lentiviral vector on the growth of SXT.Methods Thirty-five nude mice were equally divided into five groups, double-gene survivin shRNA, survivin shRNA, APC, empty vector, and blank, and injected into the left anterior axillary with respective stably transfected cell lines and human HT-29 colon carcinoma cells, all at 2×106/mL, to establish an SXT model of human HT-29 colon carcinoma.The inhibition rate of tumor growth was calculated by measuring the size and weight of the SXT, the expressions of survivin mRNA and protein in the tumor tissue detected by real time PCR and immunohistochemistry respectively, and the apoptosis of the HT-29 colon carcinoma cells determined by TUNEL.Results The mean size and weight of the SXT were significantly reduced in the double-gene survivin shRNA-APC, survivin shRNA, and APC groups as compared with the blank and empty vector groups (P<0.05), though increased in the survivin shRNA and APC groups in comparison with the double-gene group (P<0.05).The expressions of survivin mRNA and protein in the tumor tissue were remarkably lower in the double-gene survivin shRNA-APC, survivin shRNA, and APC groups than in the blank and empty vector groups (P<0.05), even lower in the double-gene group than in the survivin shRNA, and APC groups (P<0.05).The apoptosis rate of the HT-29 colon carcinoma cells was markedly up-regulated in the double-gene survivin shRNA-APC ([56.72±3.17]%), survivin shRNA ([33.64±2.03]%), and APC groups ([31.19±1.79]%) as compared with the blank ([9.89±0.31]%) and empty vector groups ([10.06±0.43]%) (P<0.05), even more significantly in the double-gene than in the survivin shRNA and APC groups (P<0.05).Conclusion The survivin shRNA-APC double gene co-expression lentiviral vector can reduce the expression level the survivin gene, promote the apoptosis of colon carcinoma cells, and suppress the growth of the subcutaneous xenotransplanted tumor.

An efficient modified route based on the targeting mechanism of antibacterial fluoroquinolones for the shift from the antibacterial activity to the antitumor one was further developed. Using a fused heterocyclic ring, s-triazolothiadiazine as a carboxyl bioisostere of ciprofloxacin, the title compounds, 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3-(6-substituted-phenyl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-3-yl)-quinolin-4(1H)-ones (5a-5e) and their corresponding N-acetyl products (6a-6e), were designed and synthesized, separately. Meaningfully, a ring-contraction of fused six-membered thiadiazine occurred by a sulfur extrusion reaction gave new tri-acetylated fused heterocycles related to pyrazolo[5, 1-c][1, 2, 4] triazoles (7a-7e). The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated for the synthesized fifteen heterocycles compared to parent ciprofloxacin by methylthiazole trazolium (MTT) assay. Interestingly, the results displayed that fifteen fused heterocyclic compounds showed more significant growth inhibitory activity (IC50 < 25.0 micromo x L(-1)) than that of parent ciprofloxacin (IC50 > 150.0 micromol x L(-1)), and the active order decreased from 7a-7e to 5a-5e to 6a-6e, respective.

Objective To study the inhibitory effect of verapamil and nicardipine on human scar fibroblast in serum-free culture and to compare the effectness of the two drugs.Methods We used MTT method to detect the effect of two drugs on human scar fibroblast proliferation:adding verapamil and nicardipine with different concentrations in the culture of fibroblasts which were in logarithmic growth phase (150,100,50,10,0μmol/L).After 24,72,and 120 h,we used MTT method to detect the cell proliferation,and converted the absorbance into growth inhibitory ratio.Results Verapamil and nicardipine showed the definite inhibition on the hypertrophic scar fibroblast (HSFB) and keloid fibroblast (KDFB) which were cultured in vitro.There was some difference in the action feature.In the earlier period,the effect of verapamil was powerful than that of nicardipine.With time,the effect did not reinforce.When fibroblast had been cultured for three to five days,the inhibition became weak.But nicardipine showed lasting inhibition on fibroblast proliferation.Conclusion Combination of verapamil with nicardipine may be a valuable method in the treatment of scar.

Objective To investigate the distribution of death among human immunodeficiency virus/acquired immuno deficiency syndrome(HIV/AIDS) cases in Guizhou Province from 1995 to 2017. Methods The HIV/AIDS death cases from 1995 to 2017 were downloaded from “Chinese National Comprehensive HIV/AIDS Prevention and care Information system” in Guizhou Province and were analyzed. Results From 1995 to 2017, Guizhou Province reported a total of 43 794 HIV/AIDS cases and 11 527 deaths according to current address. After excluding missing persons, the HIV/AIDS mortality rate of the province was 29.8%. The proportion of reported HIV/AIDS cases died in the same year ( 21995-2012=139.5, P<0.001; 22012-2015=28.2, P<0.001) and the proportion of HIV/AIDS cases ( 21995-2012=109.1, P<0.001; 22012-2014=57.2, P<0.001) who survived at the beginning but died later in the year all showed a trend being low-high-low. In the analysis of the detection history of death cases, the detection proportion of cluster of differentiation 4(CD4) T-cell and the proportion of antiviral treatment had been increasing year by year. The analysis of the cause of death found that the proportion of death caused by AIDS increased firstly and then declined, and the proportion of death due to excessive drug abuse showed a trend of declining year by year. Conclusions The mortality rate of HIV/AIDS in Guizhou Province was still high, and decreased rather slow. Expanding the coverage of HIV monitoring and screening is one of the key tasks of AIDS prevention and control. CD4+T-cell testing and free antiviral treatment should be strengthened to reduce the mortality rate of HIV/AIDS in Guizhou Province in the future.

Objective To investigate the bioequivalence of gliclazide sustained-release tablets in Chinese healthy subjects.Methods The study was designed using a single-center,open,randomized,single-dose,two-cycle,two-sequence administration method;subjects were orally administered the test/reference preparation 30 mg on an fasting or fed conditions,with self-cross-dosing.The concentration of gliclazide in human plasma was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS)method.The main pharmacokinetic parameters of gliclazide(Cmax,AUC0-t and AUC0-∞)were analyzed by non-atrioventricular model of WinNonlin.Result In the fasting study,24 subjects were recruited and 22 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in the fasting group were as follows:Cmax were(862.48±294.48)and(902.96±259.09)ng·mL-1;AUC0-t were(2.60 × 104±8 930.46)and(2.50 ×104±7 573.42)h·ng-1·mL-1;AUC0-∞ were(3.00 × 104±1.43 × 104)and(2.68 × 104±7 085.99)h·ng·mL-1.In the fed study,twenty-four subjects were enrolled and 23 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in fed group:Cmax were(1 531.74±273.49)and(1 510.87±241.08)ng·mL-1;AUC0-t were(2.78 ×104±9 565.89)and(2.76 ×104±9 821.43)h·ng·mL-1;AUC0-∞ were(3.02 ×104±1.24 ×104)and(3.02 × 104±1.30 × 104)h·ng·mL-1 h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0-t,AUC0-∞ for the test preparation and reference preparation gliclazide sustained-release tablets were all between 80％and 125％.Conclusion The test and the reference preparation of gliclazide sustained-release tablets are bioequivalent in Chinese healthy subjects.

Objective To find out the status of HIV infection,sexual behaviors with both men and women as well as condom use among currently married men who have sex with men (MSM) so as to document for HIV intervention targeting this sub-population,in Beijing,Chengdu,Harbin and Zhengzhou cities.Methods “Snowballing” sampling method was used to recruit subjects in four cities.Participants were investigated by anonymous questionnaire containing demographics,sexual orientation,both homosexual and heterosexual behaviors and condom use during the past 6 months.Blood samples from participants were used to test HIV antibodies.Results Of the 858 participants for four cities,the average age was 38.3 (SD=9.1) years.36.7％ of them had completed the junior high school or under.The percentage of participants who identified themselves as homosexual,bisexual,and heterosexual or undecided were 40.9％,54.3％ and 4.8％,respectively.The overall HIV prevalence was 8.0％,and among four cities the HIV prevalence in Chengdu was the highest ( 13.3％ ).Results from the Multiple logistic regression analysis showed that never used condoms when having anal sex with men during the past 6 months among participants who did not have a city residential card,identifying himself as having homosexual orientation,living in Harbin,having first anal sex experience before 18 years of age the range of OR value was 1.5-2.1.In addition,the faetors associated with never using condoms in vaginal sex with women during the past 6 months were as follows:being over 46 years old,not having a city residential card,living in Beijing,identifying himself as heterosexual orientated or with unknown sexual orientation,never using condoms in anal sex with men during the past 6 months,the range of OR value was 1.7-5.9.Conclusion The prevalence of HIV infection seemed to be quite high among those currently married MSM.High rates of unprotected homosexual and heterosexual behaviors might accelerate the spreading of HIV from currently married MSM to their wives.

To explore an efficient strategy for further development of anticancer fluoroquinolone candidates derived from ciprofloxacin, a heterocyclic ring as the bioisosteric replacement of C3 carboxyl group led to a key intermediate, oxadiazole thiol (5), which was further modified to the bis-oxadiazole methylsulfides (7a-7h) and the corresponding dimethylpiperazinium iodides (8a-8h), respectively. Structures were characterized by elemental analysis and spectra data, and their anticancer activities in vitro against CHO, HL60 and L1210 cancer cells were also evaluated by MTT assay. The preliminary results show that piperazinium compounds (8) possess more potent activity than that of corresponding free bases (7).
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; CHO Cells ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Ciprofloxacin ; chemistry ; Cricetinae ; Cricetulus ; Drug Design ; HL-60 Cells ; Humans ; Inhibitory Concentration 50 ; Leukemia L1210 ; Molecular Structure ; Oxadiazoles ; chemical synthesis ; chemistry ; pharmacology ; Piperazines ; chemical synthesis ; chemistry ; pharmacology

An efficient modified route based on the targeting mechanism of antibacterial fluoroquinolones for the shift from the antibacterial activity to the antitumor one was further developed. Using a fused heterocyclic ring, s-triazolothiadiazine as a carboxyl bioisostere of ciprofloxacin, the title compounds, 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3-(6-substituted-phenyl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-3-yl)-quinolin-4(1H)-ones (5a-5e) and their corresponding N-acetyl products (6a-6e), were designed and synthesized, separately. Meaningfully, a ring-contraction of fused six-membered thiadiazine occurred by a sulfur extrusion reaction gave new tri-acetylated fused heterocycles related to pyrazolo[5, 1-c][1, 2, 4] triazoles (7a-7e). The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated for the synthesized fifteen heterocycles compared to parent ciprofloxacin by methylthiazole trazolium (MTT) assay. Interestingly, the results displayed that fifteen fused heterocyclic compounds showed more significant growth inhibitory activity (IC50 < 25.0 micromo x L(-1)) than that of parent ciprofloxacin (IC50 > 150.0 micromol x L(-1)), and the active order decreased from 7a-7e to 5a-5e to 6a-6e, respective.
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; CHO Cells ; Cell Line, Tumor ; Ciprofloxacin ; pharmacology ; Cricetinae ; Cricetulus ; Fluoroquinolones ; chemical synthesis ; chemistry ; pharmacology ; HL-60 Cells ; Humans ; Inhibitory Concentration 50 ; Leukemia L1210 ; pathology ; Mice ; Structure-Activity Relationship ; Thiadiazines ; chemical synthesis ; chemistry ; pharmacology ; Triazoles ; chemical synthesis ; chemistry ; pharmacology