1.Part IV. Synthesis and antitumor evaluation of s-triazolothiadiazines and pyrazolo s-triazoles derived from ciproxacin.
Songqiang XIE ; Yinsheng CHEN ; Guoqiang WANG ; Nannan DUAN ; Xiaoyi WEN ; Tieyao CAO ; Jun YIN ; Wei WANG ; Guoqiang HU ; Wenlong HUANG
Acta Pharmaceutica Sinica 2012;47(1):66-71
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.
2.Investigation on the cognitive level of Mpox among MSM population in Shenzhen and analysis of the influencing factors in 2023
Tianlong XIA ; Shule XU ; Shaochu LIU ; Wei XIE ; Yanpeng CHENG ; Yinsheng GUO ; Jianhua LU ; Yan ZHANG
Chinese Journal of Preventive Medicine 2024;58(5):686-689
From June 16 to 30, 2023, men who have sex with men (MSM) who had visited Voluntary Counseling Testing (VCT) clinics in the Luohu, Futian and Nanshan districts of Shenzhen were included in this study to analyze their awareness of Mpox and the influencing factors. The mean age of the 262 MSM was (34.78±8.94) years, with the majority being unmarried (75.2%) and 79.0% confirmed to be infected with HIV. The awareness rates for five primary indicators, current status of Mpox, pathogen and source of infection, mode of transmission, population susceptibility, clinical manifestations and treatment were 68.4%, 84.7%, 60.3%, 87.8%, and 52.5%, respectively. The awareness rates for five secondary indicators, earliest transmission location (44.7%), main mode of transmission (54.2%), role of masks (46.9%), drug accessibility (46.6%), and self-limiting nature (38.2%) were all below 60%. The MSM population in Shenzhen perceived their likelihood of being infected (2.76±1.32) and discriminated against (3.87±1.26) as relatively low. The logistic analysis showed that the high school or vocational school education ( OR:3.094, 95 %CI:1.180-9.299), college or above education ( OR:5.360, 95% CI:2.159-15.501), and higher scores on questions affecting learning or work ( OR:2.196, 95% CI:1.409-3.599) were promoting factors for Mpox awareness, while higher scores on questions concerning the possibility of Mpox mortality ( OR:0.591, 95% CI:0.432-0.791) was the hindering factor for Mpox awareness.
3.Investigation on the cognitive level of Mpox among MSM population in Shenzhen and analysis of the influencing factors in 2023
Tianlong XIA ; Shule XU ; Shaochu LIU ; Wei XIE ; Yanpeng CHENG ; Yinsheng GUO ; Jianhua LU ; Yan ZHANG
Chinese Journal of Preventive Medicine 2024;58(5):686-689
From June 16 to 30, 2023, men who have sex with men (MSM) who had visited Voluntary Counseling Testing (VCT) clinics in the Luohu, Futian and Nanshan districts of Shenzhen were included in this study to analyze their awareness of Mpox and the influencing factors. The mean age of the 262 MSM was (34.78±8.94) years, with the majority being unmarried (75.2%) and 79.0% confirmed to be infected with HIV. The awareness rates for five primary indicators, current status of Mpox, pathogen and source of infection, mode of transmission, population susceptibility, clinical manifestations and treatment were 68.4%, 84.7%, 60.3%, 87.8%, and 52.5%, respectively. The awareness rates for five secondary indicators, earliest transmission location (44.7%), main mode of transmission (54.2%), role of masks (46.9%), drug accessibility (46.6%), and self-limiting nature (38.2%) were all below 60%. The MSM population in Shenzhen perceived their likelihood of being infected (2.76±1.32) and discriminated against (3.87±1.26) as relatively low. The logistic analysis showed that the high school or vocational school education ( OR:3.094, 95 %CI:1.180-9.299), college or above education ( OR:5.360, 95% CI:2.159-15.501), and higher scores on questions affecting learning or work ( OR:2.196, 95% CI:1.409-3.599) were promoting factors for Mpox awareness, while higher scores on questions concerning the possibility of Mpox mortality ( OR:0.591, 95% CI:0.432-0.791) was the hindering factor for Mpox awareness.
4.Pharmacodynamic study of magnesium isoglycyrrhizinate in HBV transgenic mouse model
Hongjiang XU ; Wei SHI ; Wei SONG ; Ying ZHANG ; Kaidi ZHAO ; Yinsheng ZHANG ; Ling YANG ; Jinan WANG
Journal of China Pharmaceutical University 2019;50(4):475-480
This study aims to discuss the therapeutic effect of magnesium isoglycyrrhizinate on hepatitis B virus(HBV)transgenic mouse and its effect on cellular immunity and liver inflammation. The changes of serum aspartate aminotransferase(AST)and alanine aminotransferase(ALT)activity, the difference of serum hepatitis B surface antigen(HBsAg), liver tissue HBsAg mRNA, and the pathological morphological changes of liver tissue were detected to investigate the hepatic inflammatory lesions and the efficacy of magnesium isoglycyrrhizinate in HBV transgenic mouse. Peripheral blood lymphocytes were classified by flow cytometry, and serum cytokines were detected by cytometric bead array(CBA)to explore the mechanism of magnesium isoglycyrrhizinate to reduce hepatic inflammatory lesions in HBV transgenic mouse. After grouping HBV transgenic mouse with serum transaminase activity and 35 days of continuous administration, serum transaminases level in magnesium isoglycyrrhizinate [15 mg/(kg ·d)] group was significantly lower than that in control group(P< 0. 05), serum HBsAg protein and liver tissue HBsAg mRNA increased with time, but there was no significant difference between the two groups. The main pathological changes of liver were liver cell swelling, necrosis and focal inflammatory cell infiltration, and the pathological changes of liver in magnesium isoglycyrrhizinate group were lighter than those in control group. The number of CD8+ cells in the blood of magnesium isoglycyrrhizinate group was significantly less than that in the control group(P< 0. 05)and the CD4+/CD8+ cell ratio was significantly higher than that in the control group(P< 0. 05). The content of inflammatory cytokines in serum of magnesium isoglycyrrhizinate group decreased significantly(P< 0. 05). Magnesium isoglycyrrhizinate can regulate the immune function of HBV transgenic mouse, decrease the infiltration of inflammatory cells in hepatic tissue and hepatocyte injury, but do not affect the expression of hepatocyte HBsAg.
5.Advances in the application of duck hepatitis B animal model in pharmaceutical field
Jinan WANG ; Wei SHI ; Wei SONG ; Yaqi ZHANG ; Yinsheng ZHANG ; Hongjiang XU
Journal of China Pharmaceutical University 2018;49(6):746-750
The genome, replication mode and nosogenesis of duck hepatitis B virus are similar to those of human hepatitis B virus. In addition, the natural host of duck hepatitis B virus is readily available, cheap and has a high success rate of infection. Therefore, duck hepatitis B virus-infected models have been widely used for drug screening, pharmacological and pathological studies. For drug screening, the model is easy to obtain with high infection success rate and good stability. In the pharmacological research, the model can maintain high levels of viral DNA replication in the hepatocytes and exhibit significant damaged liver phenotypes which can reflect the pharmacological effects of drugs with different mechanisms. Also in the pathologic mechanisms research, the model has entire virus life cycle and maintains a pool of covalent closed-loop DNA in the hepatocytes, which can help scientific researchers better understand human hepatitis B virus. This article reviews the applications of duck hepatitis B animal model in drug screening, pharmacological and pathological studies, also outlooks the application prospect of this model.
6.Clinical features and prognosis of paraganglioma of the urinary bladder
Zhili YANG ; Liwen LU ; Ting ZHANG ; Wenjian LUO ; Yantong HAN ; Yong ZHANG ; Lingang CUI ; Yinsheng WEI ; Teng LI ; Qingjun MENG
Journal of Modern Urology 2023;28(10):861-866
【Objective】 To explore the clinical features, treatment and prognosis of paraganglioma of the urinary bladder (PUB). 【Methods】 The clinical data of 41 PUB patients treated at our hospital during Sep.2012 and Sep.2022 were collected. The clinical features, surgical records, pathological reports and follow-up records were retrospectively analyzed. Patients’ survival was estimated with Kaplan-Meier estimator. The differences among groups were compared with Log-rank test. 【Results】 Among the 41 patients, 20 were male and 21 were female, with a median age of 52 years. All patients were treated with surgery, including transurethral resection of bladder tumor (TURBT) in 16 cases, partial cystectomy (PC) in 23 cases, and radical cystectomy (RC) in 2 cases. All patients were followed up for 4.0 to 125.0 months, with a median of 59.0 months. Local recurrence occurred in 5 patients, and distant metastasis occurred in 5 patients. Survival analysis showed that the 5-year overall survival (OS) rate and 5-year relapse-free survival (RFS) rate were 95.7% and 84.8%, respectively. Further analysis showed statistically significant differences in OS and RFS among groups with different maximum tumor diameters, growth patterns, and Ki-67 expressions (P<0.05). For patients with a maximum tumor diameter ≤2.8 cm, there was no significant difference in OS and RFS among different surgical groups. 【Conclusion】 PUB is rare, and a definitive diagnosis is based on pathology. In addition, the main treatment is surgery and the prognosis is good.