1.Antitumor activity of the recombinant rClone30-CD/5-FC system.
Zheng LU ; Tianyuan ZHANG ; Miaomiao HAN ; Fuliang BAI ; Wei WU ; Guiyou TIAN ; Guiping REN ; Deshan LI
Acta Pharmaceutica Sinica 2013;48(2):261-8
5-Flucytosine (5-FC) could be changed to 5-fluorouracil (5-FU) by cytosine deaminase (CD), the latter is able to kill cancer cells. However, there is no efficient method to deliver the CD gene into the tumor cells, which hampers the application of the suicide gene system. In this experiment, for the first time, the NDV has been utilized as a vector to deliver the CD gene into the cancer cells, the virus can infect the cancer cells specifically, replicate and assemble, while the cytosine deaminase is expressed. Then the CD converts the prodrug 5-FC into 5-FU to achieve the purpose of inhibiting tumor. Firstly, the whole genome of E. coli JM109 was extracted, and the CD gene was obtained by cloning method. Then the CD and IRES-EGFP were ligated into the pEE12.4 expression vector to become a recombinant pEE12.4IE-CD eukaryotic expression plasmid. The human liver cancer cells were transfected with the plasmid. The cells were treated with different concentrations of 5-FC, MTT method was used to determine the killing effect of CD/5-FC system on the human liver cancer cells. The cell deaths were 18.07%, 42.98% and 62.20% respectively when the concentrations of prodrug were at 10, 20 and 30 mmol x L(-1). In 5-FC acute toxicity experiment, Kunming mice were injected with different concentrations of 5-FC at intervals of 1:0.5. The LD50 of 5-FC through iv injection was determined by improved Karber's method, the LD50 was 507 mg x kg(-1) and the 95% confidence limit was 374-695 mg x kg(-1). According to the maximum LD0 dose of the LD50, the maximum safe dose was 200 mg x kg(-1). Body weight and clinic symptoms of the experimental animals were observed. These results laid the foundation to verify the antitumor effect and safety of CD/5-FC system in animal models. The CD gene was ligated into the NDV (rClone30) carrier, then the tumor-bearing animal was established to perform the tumor inhibiting experiment. The result showed that the recombinant rClone30-CD/5-FC system has a high antitumor activity in vivo. To summarize, CD gene has been cloned and its bioactivity has been confirmed in the mammalian cells. It is the first time in this study to utilize the recombinant NDV to deliver the CD gene into the tumor cells; our result proves the rClone30-CD/5-FC system is a potential method for cancer therapy.
2.A long-term clinical report of a modified unilateral cutaneous ureterostomy in bladder cancer patients receiving radical cystectomy
Shenghua LIU ; Cheng LI ; Zongtai ZHENG ; Yang YAN ; Jiang GENG ; Ming LUO ; Tianyuan XU ; Junfeng ZHANG ; Yifan CHEN ; Jianhua HUANG ; Xudong YAO
Chinese Journal of Urology 2022;43(3):207-211
Objective:To explore the long-term efficacy of a modified unilateral cutaneous ureterostomy in bladder cancer patients receiving radical cystectomy.Methods:The medical data of 104 bladder cancer patients who underwent ureterostomy in our hospital from Janurary 2013 to December 2020 were retrospectively analyzed. The patients were divided into unilateral and bilateral group. The unilateral group contained 66 cases, with 53 males and 13 females, average age (71.8±9.8) years, body mass index (BMI)(23.3±3.2)kg/m 2. The bilateral group contained 38 cases, with 33 males and 5 females, average age (75.1±10.8) years; BMI (22.7±3.0)kg/m 2. There was no significant difference in the above characteristics between the two groups ( P>0.05). The pathology, survival status, long-term complications between the two groups were compared. Quality of life was assessed during follow-up using the European Core Questionnaire for Quality of Life in Cancer Patients (EORTC QLQ-C30). Results:The unilateral group contained 46(69.7%) muscle invasive bladder cancer (MIBC) cases, 15 (22.7%) cases with lymph node metastasis, 7 (10.6%) cases with distant metastasis. The bilateral group contained 24(63.2%) muscle invasive bladder cancer(MIBC) cases, 6 (15.8%) cases with lymph node metastasis, 2 (5.3%) cases with distant metastasis. There was no significant difference in disease specific survival between the two groups ( P>0.05). During the follow-up, the incidence of overall complication rate in the unilateral group was significantly lower than that in the bilateral group [43.9% (29/66) vs. 63.2% (24/38), P<0.001]. The incidence of pyelonephritis in unilateral group was significantly lower than that in the bilateral group [16.6%(11/66) vs. 42.1%(16/38), P=0.006]. There was no statistical significance in terms of quality of life before operation in the two groups. After operation, both physical function score[(54.9±7.1) vs.(49.2±6.7)] and emotional function score [(63.1±6.4) vs.(59.9±6.7)] in unilateral group were higher than that in bilateral group ( P<0.05). Conclusions:The modified unilateral cutaneous ureterostomy could achieve relatively low complication rate, and improve the quality of life to some extent compared with bilateral ureterostomy.
3.Establishment of quantitative analysis method and prediction of potential mechanism for quality control components of Tenghuang jiangu capsules
Lin ZHOU ; Xiaohui WANG ; Zhi SUN ; Lianping XUE ; Jianwen JIN ; Jing WU ; Xiaojing LI ; Tianyuan ZHENG ; Xiaojian ZHANG
China Pharmacy 2022;33(22):2743-2747
OBJECTIVE To establish a quantitative analysis method for the quality control components in Tenghuang jiangu capsules, and predict the possible action mechanism of the quality control components. METHODS Seven key quality control components in Tenghuang jiangu capsules were quantitatively analyzed by UHPLC-Q-Orbitrap HRMS. The “component-target” network was constructed based on network pharmacology, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene ontology (GO) function enrichment analysis were further conducted to find the key signaling pathways. RESULTS The average contents of succinic acid, hyperoside, gallic acid, kaempferol, naringin, naringenin and protocatechuic acid in 20 batches of Tenghuang jiangu capsules were 520.92, 67.67, 129.48, 4.74, 397.45, 5.66 and 376.62 μg/g, respectively. The results of network pharmacology showed that the 62 key target genes of the quality control components of the drug included AKT1, TNF, VEGFA, MMP9, PTGS2, etc. They were mainly enriched in cytokine receptor interaction, nuclear factor, tumor necrosis factor, interleukin 17, rheumatoid arthritis, Toll-like receptor and other signal pathways, involving inflammatory reaction, signal transduction, protein phosphorylation and other biological processes, kytoplasm, cell membrane and other cell components, as well as enzyme activity, energy activity and other molecular functions. CONCLUSIONS The established UHPLC- Q-Orbitrap HRMS method can be used for the quantitative analysis of the quality control components of Tenghuang jiangu capsule. Its quality control components may be mapped to inflammatory pathways related to bone diseases such as rheumatoid arthritis and Toll-like receptors through AKT1, TNF, VEGFA and other key targets, so as to play a therapeutic role.
4.Gender differences in mortality following tanscatheter aortic valve replacement (TAVR): a single-centre retrospective analysis from China.
Qi LIU ; Yali WANG ; Yijian LI ; Tianyuan XIONG ; Fei CHEN ; Yuanweixiang OU ; Xi WANG ; Yijun YAO ; Kaiyu JIA ; Yujia LIANG ; Xin WEI ; Xi LI ; Yong PENG ; Jiafu WEI ; Sen HE ; Qiao LI ; Wei MENG ; Guo CHEN ; Wenxia ZHOU ; Mingxia ZHENG ; Xuan ZHOU ; Zhengang ZHAO ; Chen MAO ; Feng YUAN
Chinese Medical Journal 2023;136(20):2511-2513
5.Peri-procedural myocardial injury predicts poor short-term prognosis after TAVR: A single-center retrospective analysis from China.
Qi LIU ; Kaiyu JIA ; Yijun YAO ; Yijian LI ; Tianyuan XIONG ; Fei CHEN ; Yuanweixiang OU ; Xi WANG ; Yujia LIANG ; Xi LI ; Yong PENG ; Jiafu WEI ; Sen HE ; Qiao LI ; Wei MENG ; Guo CHEN ; Wenxia ZHOU ; Mingxia ZHENG ; Xuan ZHOU ; Yuan FENG ; Mao CHEN
Chinese Medical Journal 2023;136(24):3013-3015