1.Correlation between serum VEGF level and clinical symptoms in patients with first-episode drug-naive schizophrenia of different genders
Peng CHEN ; Huimin ZHAO ; Xuyuan YIN ; Zhenhua ZHU ; Qi QI ; Caixia JIANG ; Ying YUAN ; Linghua KONG ; Zhenyong GAO ; Ping YANG ; Qiufang JIA ; Li HUI
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(2):136-140
Objective:To investigate the level of serum vascular endothelial growth factor (VEGF) and its correlation with clinical symptoms in patients with first-episode drug-naive schizophrenia patients of different genders.Methods:From January 2016 to October 2019, a total of 81 first-episode drug-naive schizophrenia patients(patient group, 41 male, 40 female) and 64 healthy controls (control group, 40 male, 24 female) were included in this study.The serum level of VEGF was detected with flow cytometric bear array (CBA). Positive and negative symptom scale (PANSS) was used to evaluate the relevant clinical symptoms of patients.SPSS 22.0 software was used for statistical analysis.Independent sample t-test and nonparametric test were used for comparison between groups.The relationship between VEGF and clinical variables was analyzed by Pearson correlation analysis and Spearman correlation analysis. Results:The level of serum VEGF in the patient group was significantly lower than that in the control group(148.08(75.89, 208.61)pg/mL, 179.94(99.14, 318.41)pg/mL, Z=-2.20, P=0.028). The total PANSS score((82.71±17.30), (73.45±16.36), t=2.473, P=0.016)and cognitive score((7.88±3.36), (6.23±2.81), t=2.402, P=0.019) in male patients were higher than those in female patients.There was a negative correlation between VEGF level and PANSS negative symptom score in the patient group( r=-0.228, P=0.041), as well as significant negtive correlation between VEGF level and cognitive score in male patients( r=-0.425, P=0.007). Conclusion:The level of serum VEGF is reduced in first-episode patients with schizophrenia, which influences their negative symptom. Moreover, the decline in serum VEGF level is implicated in cognitive impairments in male patients with first-episode schizophrenia.
2.Optimization of Preparation Technology of Near-infrared Light Response-based Doxorubicin Hydrochloride Nano-liposomes
Xiali ZHU ; Shasha WANG ; Linghua LI ; Yanyan BA ; Liming LIU ; Yongyan JIA
China Pharmacy 2019;30(10):1312-1315
OBJECTIVE: To establish a methaod for content determination of doxorubicin hydrochloride nano-liposomes, and to optimize its preparation technology. METHODS: The contents of doxorubicin hydrochloride nano-liposomes was determined by UV spectrophotometry. The membrane dispersion method was used to prepare doxorubicin hydrochloride nano-liposomes. Using particle size, encapsulation efficiency and drug-loading amount as indexes, the weight ratio of phospholipid to drug (mg/mg), the weight ratio of phospholipid to cholesterol (mg/mg) and ultrasonic time (min) as factors, central composite design-response surface methodology was used to optimize the preparation technology. The photothermal conversion effect of doxorubicin hydrochloride nano-liposomes was investigated by near infrared irradiation. RESULTS: The linear range of doxorubicin hydrochloride were 1.01-16.16 μg/mL(r=0.999 7); precision, stability and reproducibility tests were all in line with the requirments of Chinese Pharmacopoeia. The optimal preparation technology included that the weight ratio of phospholipid to drug was 13.30 ∶ 1(mg/mg); the weight ratio of phospholipid to cholesterol was 4.09 ∶ 1 (mg/mg); the ultrasonic time was 10 min. Under this technology, the particle size and drug-loading amount of doxorubicin hydrochloride nano-liposomes were (200.5±25.1) nm and (11.02±0.20)%, relative errors of which to predicted value (196.3 nm, 10.68%) were 1.82% and 1.63%. The consistency between measured value and predicted value was good. Doxorubicin hydrochloride nano-liposomes exhibited concentration- dependent and time-dependent photothermal conversion characteristics under near infrared irradiation at 808 nm. CONCLUSIONS: Established method is simple and good accuracy. The optimized preparation technology is simple and feasible.
3.Preparation of Adriamycin Hydrochloride Magnetic Thermosensitive Liposome Based on TiO 2@Fe3O4 and Its Physicochemical Properties,Magnetic Effect and Photothermal Effect Study
Xiali ZHU ; Huijuan ZHANG ; Shasha WANG ; Linghua LI ; Yongyan JIA
China Pharmacy 2019;30(20):2752-2757
OBJECTIVE: To prepare Adriamycin hydrochloride (DOX) magnetic thermosensitive liposome (MTSL), investigate its physicochemical properties, magnetic effect and photothermal effect, so as to provide reference for tumor chemo- therapy and photodynamic/photothermal therapy. METHODS: Using DOX as model drug, TiO2@Fe3O4 as photosensitizers and magnetic materials, DOX-TiO2@Fe3O4-MTSL was prepared with membrane dispersion method. The morphology and dispersibility were observed; particle size and Zeta potential were detected; encapsulation efficiency of the liposome were determined by centrifugal ultrafiltration and HPLC. Its paramagnetism property was also detected by magnetometer. Compared with DOX solution, in vitro release behavior of the liposome was investigated by dialysis method, and the release curves at different temperatures (at 37, 43 ℃) were compared. The photothermal conversion effect of the liposome and the production of reactive oxygen species (ROS) in human breast cancer MCF-7 cells were investigated by near infrared laser irradiation at 808 nm. RESULTS: Prepared DOX-TiO2@Fe3O4-MTSL was brown-black with good water dispersion, and was spherical in shape and uniform in size under electron microscopy. Average particle size was 250.6 nm; polydispersity index was 0.107; Zeta potential was (-7.76±3.41)mV; encapsulation efficiency was (92.3±3.2)%. Under the external magnetic field, the liposome could move in a directional direction and had obvious paramagnetism. Compared with DOX solution, the liposomes released slowly and showed obvious sustained- release characteristics. Compared with at 37 ℃, the drug release of liposome speeded up significantly at 43 ℃.With the increase of laser (808 nm) irradiation time, the temperature of the liposome kept rising, which had obvious photothermal conversion effect and could induce the increase of ROS in MCF-7 cells. CONCLUSIONS: DOX-TiO2@Fe3O4-MTSL is prepared succe- ssfully, which has uniform appearance, good physical and chemical properties. It has obvious paramagnetism sustained release effect and photothermal conversion efficiency, and can promote ROS production in MCF-7 cells under near infrared laser irradiation at 808 nm.
4.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