1.Study on screening simulated epitopes of protective antigens of Schistosoma japonicum and their immuno-protective effect
Xiang LIU ; Yilan HU ; Li HE ; Mingsen JIANG ; Mengxiang YANG
Chinese Journal of Schistosomiasis Control 1989;0(01):-
Objective To study the immuno-protective effect against Schistosoma japonicum challenge of the positive monoclonal phages which were screened from the 12 mers-phage random peptide library by the new model rabbit serum. Methods The new model was established by injecting the Schistosoma japonicum infection rabbits with inhibitor of phenol oxidose. Positive clones immunoscreened with the new model rabbit sera were absorbed by SEA immune rabbit sera, and 14 clones selected randomly from them were compared and their antigenic ability was identified by ELISA. The two best positive monoclonal phages (No.8, No.13) recognized by the new model rabbit sera were selected to immunize Kunming mice by subcutaneously injecting 1?10~15 pfu positive phages at 0, 2nd, 4th week respectively. After 4 weeks of the last immunity,each mouse was challenged with 40?1 S.japonicum cercariae. All mice were sacrificed after 42 days and the reduction rates of adult worms and the liver eggs were investigated. Results The positive phage clones after immune absorption were weakly recognized by the SEA immune rabbit sera. The 14 monoclonal phages were recognized by the rabbit sera of the new model and the normal model. Especially No.8, No.13 were strongly recognized by the rabbit sera of the new model,while weakly recognized by the SEA immune rabbit sera. The reduction rates of adult worms and liver eggs induced by the monoclonal phage No.13, the monoclonal phage No.8 and the original peptide library were 35.81% and 63.32%, 32.09% and 52.02%, 14.90% and 30.64%, respectively. Conclusion Most clones of simulated epitopes of SEA can be removed by absorbing positive clones with SEA immune rabbit serum .The 14 monoclonal phages from the new model contain the simulated S.japonicum epitope. The two monoclonal phages have higher reduction rates of adult worms and eggs than original 12 mers-phage random peptide library and the positive polyclonal phages.[
2.Comparison of bone marrow smear, biopsy and flow cytometry in diagnosis of lymphoma patients with bone marrow involvement
Yunfei HU ; Yunhong HUANG ; Gang NI ; Jinhua LONG ; Mengxiang CHEN ; Fang YANG
Journal of Leukemia & Lymphoma 2013;22(12):729-731,735
Objective To compare the effectiveness,correlativity,and acceptability of the three methods:bone marrow smear,biopsy and flow cytometry in diagnosis of lymphoma patients with bone marrow involvement.Methods 68 cases of early stage lymphoma were studied by observing and comparing positive rates of the three methods:bone marrow smear,biopsy and flow cytometry.Results After confirming the bone marrow involvement,the positive rates for the 68 cases using bone marrow smear,biopsy and flow cytometry were 16.2 % (11/68),33.8 % (23/68) and 10.3 % (7/68) respectively.Bone marrow biopsy had the highest positive rate compared to the other methods.It was statistically significant when comparing the differences of the 3 methods (P < 0.05).According to the correlativity analysis of the 3 methods,bone marrow smear and biopsy correlated with each other (P =0.002),while flow cytometery did not (P =0.270).Conclusions Morphological examination of the bone marrow smear is a fundamental method to test bone marrow involvement in lymphoma.Bone marrow biopsy creates the highest positive rate and has clear advantage compared to the other methods,however,bone marrow smear must be used at the same time as a complement.
3.BSD2000 deep hyperthermia combined with chemotherapy of PT regimen in patients with non-small cell lung cancer.
Mengxiang YANG ; Jun ZHAO ; Yanwen WANG
Chinese Journal of Lung Cancer 2010;13(2):132-135
BACKGROUND AND OBJECTIVEThe aim of this study is to determine the short-term efficacy, toxicity and the rate of life-quality improvement of BSD2000 deep hyperthermia combined with chemotherapy of PT regimen in patients with non-small cell lung cancer (NSCLC) by comparation with PT regimen alone.
METHODSSixty patients with NSCLC were randomly divided into the treatment group and control group, with 30 each. The treatment group was treated with chemotherapy (paclitaxel: 135 mg/m2 ivdirp 3 h qd d1+cisplatin: 20 mg/m2 ivdirp qd d1-5) in combination with BSD2000 deep hyperthermia, and hyperthermia was positioned precisely and maintained for 60 min (2 times a cycle: d1, 4 after the end of chemotherapy within two hours). The control group was treated with chemotherapy alone. Treatment response in both groups were evaluated as well as side-effects after 3 cycles. By observing the results, comparing response rate, toxic side effects and quality of life improvement rate in two groups.
RESULTSThe efficiency and the rate of life-quality improvement in the treatment group were 63.33%, 76.67% respectively, and 36.67%, 40.00% in the control group respectively. There were significant differences between two groups (P < 0.05). The main side-effects were myelosuppression and gastrointestinal reactions, no significant difference between two groups (P > 0.05).
CONCLUSIONBSD2000 deep hyperthermia combined with chemotherapy in patients with NSCLC can significantly increase the efficacy, response rate and quality of life improvement and without increasing side-effects compared to chemotherapy alone.
Aged ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; therapy ; Female ; Humans ; Hyperthermia, Induced ; Lung Neoplasms ; drug therapy ; therapy ; Male ; Paclitaxel ; therapeutic use ; Treatment Outcome
4.Determination of endogenous glutathione in rat plasma by a new derivative LC-MS/MS method
Pengyao XU ; Yang YANG ; Mengxiang SU ; Bin DI
Journal of China Pharmaceutical University 2018;49(2):209-214
To develop a rapid and sensitive liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the determination of endogenous glutathione in rat plasma. Glycyltyrosine was used as the internal standard(IS)and 4-(N-maleimido)phenyl trimethylammonium iodide(MPTA)was used as the derivation reagent. Chromatographic separation was achieved on a Zorbax HILIC PLUS column(4. 6 mm×100 mm, 3. 5 μm)and the mobile phase consisted of acetonitrile and 0. 1% formic acid(75 ∶25)pumped at a flow rate of 1. 0 mL/min. Detection was carried out on a triple quadrupole tandem mass spectrometer by selected reaction monitoring(SRM)in the can meet positive ion mode. The linearity ranged from 3. 000 to 2 000 ng/mL(r=0. 997 1); and the limit of detection of glutathione in rat plasma was 10 pmol/L. Matrix effect, stability, precision and accuracy of the method met the requirements. The proposed method was proved to be selective and sensitive, which is suitable for the quantification of endogenous glutathione in rat plasma.
5.Hepatic retinaldehyde deficiency is involved in diabetes deterioration by enhancing PCK1- and G6PC-mediated gluconeogenesis.
Hanyu YANG ; Mengxiang SU ; Ming LIU ; Yun SHENG ; Liang ZHU ; Lu YANG ; Ruijing MU ; Jianjun ZOU ; Xiaodong LIU ; Li LIU
Acta Pharmaceutica Sinica B 2023;13(9):3728-3743
Type 2 diabetes (T2D) is often accompanied with an induction of retinaldehyde dehydrogenase 1 (RALDH1 or ALDH1A1) expression and a consequent decrease in hepatic retinaldehyde (Rald) levels. However, the role of hepatic Rald deficiency in T2D progression remains unclear. In this study, we demonstrated that reversing T2D-mediated hepatic Rald deficiency by Rald or citral treatments, or liver-specific Raldh1 silencing substantially lowered fasting glycemia levels, inhibited hepatic glucogenesis, and downregulated phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) expression in diabetic db/db mice. Fasting glycemia and Pck1/G6pc mRNA expression levels were strongly negatively correlated with hepatic Rald levels, indicating the involvement of hepatic Rald depletion in T2D deterioration. A similar result that liver-specific Raldh1 silencing improved glucose metabolism was also observed in high-fat diet-fed mice. In primary human hepatocytes and oleic acid-treated HepG2 cells, Rald or Rald + RALDH1 silencing resulted in decreased glucose production and downregulated PCK1/G6PC mRNA and protein expression. Mechanistically, Rald downregulated direct repeat 1-mediated PCK1 and G6PC expression by antagonizing retinoid X receptor α, as confirmed by luciferase reporter assays and molecular docking. These results highlight the link between hepatic Rald deficiency, glucose dyshomeostasis, and the progression of T2D, whilst also suggesting RALDH1 as a potential therapeutic target for T2D.
6.Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.
Chengyuan GU ; Zengjun WANG ; Tianxin LIN ; Zhiyu LIU ; Weiqing HAN ; Xuhui ZHANG ; Chao LIANG ; Hao LIU ; Yang YU ; Zhenzhou XU ; Shuang LIU ; Jingen WANG ; Linghua JIA ; Xin YAO ; Wenfeng LIAO ; Cheng FU ; Zhaohui TAN ; Guohua HE ; Guoxi ZHU ; Rui FAN ; Wenzeng YANG ; Xin CHEN ; Zhizhong LIU ; Liqiang ZHONG ; Benkang SHI ; Degang DING ; Shubo CHEN ; Junli WEI ; Xudong YAO ; Ming CHEN ; Zhanpeng LU ; Qun XIE ; Zhiquan HU ; Yinhuai WANG ; Hongqian GUO ; Tiwu FAN ; Zhaozhao LIANG ; Peng CHEN ; Wei WANG ; Tao XU ; Chunsheng LI ; Jinchun XING ; Hong LIAO ; Dalin HE ; Zhibin WU ; Jiandi YU ; Zhongwen FENG ; Mengxiang YANG ; Qifeng DOU ; Quan ZENG ; Yuanwei LI ; Xin GOU ; Guangchen ZHOU ; Xiaofeng WANG ; Rujian ZHU ; Zhonghua ZHANG ; Bo ZHANG ; Wanlong TAN ; Xueling QU ; Hongliang SUN ; Tianyi GAN ; Dingwei YE
Chinese Medical Journal 2023;136(10):1207-1215
BACKGROUND:
LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.
METHODS:
We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.
RESULTS:
On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).
CONCLUSION:
LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT04563936.
Humans
;
Male
;
Antineoplastic Agents, Hormonal/therapeutic use*
;
East Asian People
;
Gonadotropin-Releasing Hormone/agonists*
;
Goserelin/therapeutic use*
;
Prostate-Specific Antigen
;
Prostatic Neoplasms/drug therapy*
;
Testosterone