1.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
2. 1, 8-CineoIe improves endothelial cell injury induced by high glucose via regulating autophagy
Xiao-Mei SONG ; Hong YANG ; Qiu-Shuang LONG ; Guan-Qin FANG ; Ge GAO ; Shi-Quan GAN ; Yan CHEN ; Xiang-Chun SHEN ; Xiao-Mei SONG ; Qiu-Shuang LONG ; Guan-Qin FANG ; Ge GAO ; Shi-Quan GAN ; Yan CHEN ; Xiang-Chun SHEN ; Hong YANG
Chinese Pharmacological Bulletin 2021;37(4):472-477
Aim To investigate the protective effect of 1, 8-Cineole on the injury of human aortic endothelial cells (HAECs) induced by high glucose (HG) via regulating autophagy. Methods Cells were incubated with different doses of 1, 8-Cineole followed by exposing to HG for 60 h, and MTT assay was used to analyse cell viability, lactate dehydrogenase (LDH) was used to detect cytotoxicity, and Western blot was used to detect Beclin1, LC3-II/I, p62, caspase-3 and caspase-9 expressions. Autophagy inhibitor (chloroquine, CQ) was treated on HAECs, and the expressions of Beclinl, LC3-II/I, p62, caspase-3 and caspase-9 were measured by Western blot. Results 1, 8-Cineole increased cell viability, reduced the content of LDH, activated autophagy and inhibited apoptosis. Compared with control group, the expression of Beclinl, LC3-II/I, p62, caspase-3 and caspase-9 in CQ group increased. Simultaneously, the expression of above-mentioned between CQ + HG group and CQ + HG + CH group. Conclusions 1, 8-Cineole has protective effect on the injury of HAECs induced by high glucose, and its effect is related to improving autophagy flux.
3.Essential Oil from Alpinia zerumbet Rhizome Inhibits Macrophage-derived Foam Cell Formation Via Modulating Expression of CD36 and ABCA1
Shi-quan GAN ; Sheng-quan WANG ; Guang-qiong ZHANG ; Hong-run AN ; Ling-yun FU ; Chao-da XIAO ; Yan CHEN ; Ling TAO ; Xiang-chun SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(4):64-69
Objective::To clarify the inhibitory effect of essential oil from
4. Effect of Oxymatrine in Inhibiting Proliferation and Migration of HT-29 Cells Induced by Insulin
Di PAN ; Wen ZHANG ; Rong ZHANG ; Shi-quan GAN ; Yan CHEN ; Nen-ling ZHANG ; Yi-ni XU ; Xiang-chun SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(24):36-42
Objective:To investigate the effect of oxymatrine (OMT) on the proliferation and migration of human colon cancer cell line HT-29 under Type Ⅱ diabetes environment by co-culturing HT-29 with insulin to simulate hyperinsulinemia. Method:The effect of OMT (2, 4, 8 mmol·L-1) on insulin-induced proliferation of HT-29 was detected by methyl thiazolyl tetrazolium (MTT) assay and cloning assay. The morphology change and cell migration were evaluated under microscope and by wound healing assay. The Annexin V/propidium iodide(PI) assay was used to detect the change of insulin-induced HT-29 cell cycle and apoptosis. Western blot was performed to validate the expression of cell cycle-related protein and cell migration protein. Result:Insulin significantly increased growth of HT-29 (P<0.05). Compared with insulin group, OMT with 2, 4, 8 mmol·L-1 showed a significant inhibitory effect in this model (P<0.05). In addition, OMT blocked HT-29 cell cycle in G0/G1 phase (P<0.05), and showed a slight apoptotic effect. Western blot showed that the down-regulation of Cyclin D1, CDK4 and the up-regulation of p27 by OMT might involve the growth inhibition mechanism. Furthermore, OMT reduced the migration of insulin-induced HT-29 according to wound healing assay(P<0.05). Decreased Vimentin (P<0.05)and increased E-cadherin(P<0.05)might be correlated with the migration restrain. Conclusion:OMT can inhibit the proliferation and migration of insulin-induced HT-29 cells. The changes of cell cycle and migration related proteins may be correlated with the mechanism.
5. Preparation of Oxymatrine Phospholipid Complex Solid Lipid Nanoparticles Lyophilized Powder and Evaluation of Its Quality
Jun-li YAN ; Wan-rong LI ; Jia-jia YANG ; Yi WANG ; Zhi-yong HE ; Feng JIANG ; Xue ZHOU ; Lin-jing WU ; Shi-quan GAN ; Heng WANG ; Xiang-chun SHEN ; Ling TAO
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(7):146-152
Objective: To prepare oxymatrine phospholipid complex solid lipid nanoparticles(OMT-PC-SLN) lyophilized powder and evaluate its pharmaceutical properties. Method: Pseudo-ternary phase diagram was employed to optimize the formula of microemulsion;single factor experiments were adopted to optimize the formulation process of OMT-PC-SLN lyophilized powder with encapsulation efficiency as index;the morphology of this preparation was observed by transmission electron microscope(TEM).The particle size was measured by particle size analyzer and the in vitro release performance of OMT-PC-SLN lyophilized powder was examined. Result: Optimal formulation process was as following:taking soybean phospholipid and polyethylene glycol 15-hydroxystearate(Kolliphor HS 15) as the emulsifier,ethanol as co-emulsifier,ratio of emulsifier to co-emulsifier(Km)=3:2,oil phase:(emulsifier+co-emulsifier)=1:9,oxymatrine phospholipid complex-stearic acid-soybean phospholipid-Kolliphor HS 15-ethanol(30:100:180:360:360);taking 50 mL of 4%mannitol solution as the external aqueous phase,ice bath stirring at 1 000 r·min-1 and solidifying for 1 h,precooled at -20℃ for 24 h,took out and dried for 24 h.OMT-PC-SLN lyophilized powder was spherical in appearance with encapsulation efficiency of (38.09±1.24)%,average particle size of 785.5 nm,polydispersity coefficient(PDI) of 0.456 and the Zeta potential of -24.82 mV.The cumulative release rates of OMT-PC-SLN lyophilized powder were 72.63%at 2 h and 98.42%at 12 h;the cumulative release rate of oxymatrine(crude drug) was 98.60%at 2 h. Conclusion: This optimized formulation process of OMT-PC-SLN lyophilized powder is stable with good repeatability;compared with oxymatrine,OMT-PC-SLN lyophilized powder has a certain sustained-release effect.
6.Lung Involvement Is an Early Clue to Severe Dengue
Yun-feng SHI ; Xiao-han SHI ; Lai-zhi ZHOU ; Jun-hui BA ; Wei-qiang GAN ; Yu-wei Tong ; Ben-quan WU
Journal of Sun Yat-sen University(Medical Sciences) 2019;40(5):774-780
【Objective】To investigate the differences of lung involvement between dengue and severe dengue.【Methods】227 dengue patients admitted in The Third Affiliated Hospital of Sun Yat-sen University from July 2014 to October 2018 were enrolled. The clinical characteristics,treatment and outcome of the patients were analyzed to explore the differences of lung involvement between dengue and severe dengue (SD). 【Results】 The rate of old age ,smoking ,hypertension,diabetes and cerebrovascular disease was higher in dengue with lung involvement group(DWLI)than dengue without lung involvement group(DWOLI)(χ2 were 25.146,3.847,10.326,7.177,and 5.355,P was 0.050 for smoking,the others were < 0.05). The rate of cough and breathlessness was higher in DWLI(χ2 were 11.465 and 6.068,P were 0.001 and 0.014),as well as in SD subgroup(χ2 were 4.585 and 6.717,P were 0.032 and 0.010). C-reactive protein and procalcitonin were increased in DWLI(Z were - 2.591 and - 3.033,P were 0.010 and 0.002). The rate of pleural effusion was higher in SD subgroup(χ2 = 4.987,P = 0.026). Bilateral lung infiltration was correlated with SD(χ2 = 5.910,P =0.015). The rate of acute liver injury,acute kidney injury and multi-organ dysfunction syndrome(MODS)was higher in DWLI(χ2 were 7.044,7.059,and 11.315,P were 0.008,0.008 and 0.001). The rate of anti-virus,anti-bacteria and combined therapy was higher in DWLI(χ2 were 13.156,32.845,and 12.684,P all were < 0.001).【Conclusion】Dengue patients who were with old age,smoking,or suffered from underlying disease of hypertension,diabetes and cerebrovascular disease were vulnerable to lung involvement. Cough,breathlessness,pleural effusion and bilateral lung infiltration were signs of severe dengue. Attention should be paid to dengue with lung involvement.
7.Study on catabolism and clearance of enalapril maleate tablets in vivo tracked by surface-enhanced Raman scattering spectrometry
Sheng GAN ; Qing-Niao LAI ; Xiao-Guang SHI ; Ting HAN ; Chao-Quan WU
The Chinese Journal of Clinical Pharmacology 2016;32(12):1132-1135
Objective To track the catabolic route and clearance of ena-lapril maleate tablets in vivo by surface -enhanced Raman scattering spectrometry , and put forward proposal to its safe medication.Methods The urine and feces of 15 patient exemplars was collected , pre-processed , blended with an equal volume of surface -enhancer , and tested at the identified peak of enalapril maleate of (1470 ±2 ) /cm.Then the clearance of active pharmaceutical ingredient was calculated and analyzed .Results The methodical recovery was high and the relevant standard deviation was within 3%.The active pharmaceutical ingredient was in good linear at the concentration of 5~100μg· mL-1 in urine and in feces, and the limit of detection was 0.5 μg · mL-1 and 1.3μg· mL-1 , respectively.Enalapril was effective to 11 exemplars, while its clinical effect was not responded on 4 exemplars.Conclusion The method is proved to be prompt and rapid , appropriate to the catabolic analysis in vivo and clinical evaluation to angiotensin -converting -enzyme Ⅰinhibitors.
8.Elevated nocturnal and morning blood pressure in patients with obstructive sleep apnea syndrome.
Quan-Ying HE ; Jing FENG ; Xi-Long ZHANG ; Zong-An LIANG ; Shao-Guang HUANG ; Jian KANG ; Guang-Fa WANG ; Li-Qiang ZHANG ; Li-Jun MA ; Bei WANG ; Qi-Chang LIN ; Jin-Nong ZHANG ; Hui-Guo LIU ; Yuan-Ming LUO ; Jian-Hong LIU ; Shi WANG ; Gao-Hui XIAO ; Gan LU ; Jin ZHANG ; Xue-Wei FENG ; Bao-Yuan CHEN
Chinese Medical Journal 2012;125(10):1740-1746
BACKGROUNDThe nocturnal nondipping and elevated morning blood pressure (BP) in patients with obstructive sleep apnea syndrome (OSAS) have not yet been well investigated in Chinese patients. This study aimed to describe the BP profile, and to elucidate the relationships between daytime BP and nighttime BP, and between evening BP and morning BP in patients with OSAS.
METHODSTwenty teaching hospital sleep centers in China were organized by the Chinese Medical Association to participate in this study and 2297 patients were recruited between January 2004 and April 2006. BP assessments were made at four time points (daytime, evening, nighttime and morning) and polysomnography (PSG) was performed and subjects were classified into four groups by their apnea-hypopnea index (AHI): control, n = 213 with AHI < 5; mild, n = 420 with AHI ≥ 5 and < 15; moderate, n = 460 with AHI ≥ 15 and < 30; and severe, n = 1204 with AHI ≥ 30. SPSS 11.5 software package was used for statistical analysis and figure drawing.
RESULTSAll the average daytime, nighttime, evening and morning BPs were positively correlated with AHI and negatively correlated with nadir nocturnal oxygen saturation. The ratios of nighttime/daytime and morning/evening average BP were positively correlated with AHI. The ratio of nighttime/daytime systolic BP became a "reversed BP dipping" pattern until the classification reached severe, while the ratio of nighttime/daytime diastolic BP became reversed at moderate. Similarly, the ratio of morning/evening diastolic BP becomes reversed even at mild.
CONCLUSIONSOSAS may result in higher BP levels at all four time points. The ratios of nighttime/daytime and morning/evening BP increase with increased AHI. The increasing of diastolic BP, which is inclined to rise more quickly, is not parallel with increasing systolic BP.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anthropometry ; Blood Pressure ; physiology ; Female ; Humans ; Hypertension ; physiopathology ; Male ; Middle Aged ; Sleep Apnea, Obstructive ; physiopathology ; Young Adult
9.Elevated nocturnal and morning blood pressure in patients with obstructive sleep apnea syndrome
Quan-Ying HE ; Jing FENG ; Xi-Long ZHANG ; Zong-An LIANG ; Shao-Guang HUANG ; Jian KANG ; Guang-Fa WANG ; Li-Qiang ZHANG ; Li-Jun MA ; Bei WANG ; Qi-Chang LIN ; Jin-Nong ZHANG ; Hui-Guo LIU ; Yuan-Ming LUO ; Jian-Hong LIU ; Shi WANG ; Gao-Hui XIAO ; Gan LU ; Jin ZHANG ; Xue-Wei FENG ; Bao-Yuan CHEN
Chinese Medical Journal 2012;(10):1740-1746
Background The nocturnal nondipping and elevated morning blood pressure (BP) in patients with obstructive sleep apnea syndrome (OSAS) have not yet been well investigated in Chinese patients.This study aimed to describe the BP profile,and to elucidate the relationships between daytime BP and nighttime BP,and between evening BP and morning BP in patients with OSAS.Methods Twenty teaching hospital sleep centers in China were organized by the Chinese Medical Association to participate in this study and 2297 patients were recruited between January 2004 and April 2006.BP assessments were made at four time points (daytime,evening,nighttime and morning) and polysomnography (PSG) was performed and subjects were classified into four groups by their apnea-hypopnea index (AHI):control,n=213 with AHI<5; mild,n=420 with AHI ≥5 and<15; moderate,n=460 with AHI≥15 and<30; and severe,n=1204 with AHI >30.SPSS 11.5 software package was used for statistical analysis and figure drawing.Results All the average daytime,nighttime,evening and morning BPs were positively correlated with AHI and negatively correlated with nadir nocturnal oxygen saturation.The ralios of nighttime/daytime and morning/evening average BP were positively correlated with AHI.The ratio of nighttime/daytime systolic BP became a “reversed BP dipping” pattern until the classification reached severe,while the ratio of nighttime/daytime diastolic BP became reversed at moderate.Similarly,the ratio of morning/evening diastolic BP becomes reversed even at mild.Conclusions OSAS may result in higher BP levels at all four time points.The ratios of nighttime/daytime and morning/evening BP increase with increased AHI.The increasing of diastolic BP,which is inclined to rise more quickly,is not parallel with increasing systolic BP.
10.Relationship of daytime blood pressure and severity of obstructive sleep apnea among Chinese: a multi-center investigation in China.
Quan-ying HE ; Jing FENG ; Xi-long ZHANG ; Zong-an LIANG ; Shao-guang HUANG ; Jian KANG ; Guang-fa WANG ; Li-qiang ZHANG ; Li-jun MA ; Bei WANG ; Qi-chang LIN ; Jing-nong ZHANG ; Hui-guo LIU ; Yuan-ming LUO ; Jian-hong LIU ; Shi WANG ; Gao-hui XIAO ; Gan LU ; Jin ZHANG ; Xue-wei FENG ; Bao-yuan CHEN ; null ; null ; null
Chinese Medical Journal 2010;123(1):18-22
BACKGROUNDEpidemiologic studies have shown an independent and definite association between obstructive sleep apnea (OSA) and hypertension. This study aimed to define the association between daytime blood pressure and severity of OSA in Chinese population in mainland of China.
METHODSTwenty university hospital sleep centers in mainland of China were invited by the Chinese Medical Association (CMA) to participate in this epidemiologic study and 2297 consecutive patients (aged 18 - 85 years; 1981 males and 316 females) referred to these twenty sleep centers for evaluation of OSA between January 2004 and April 2006 were prospectively enrolled. Nocturnal polysomnography was performed in each patient, and disease severity was assessed based on the apneahypopnea index (AHI). These patients were classfied into four groups: nonapneic control (control, n = 257) with AHI < or = 5 episodes/hour; mild sleep apnea (mild, n = 402) with AHI > 5 and < or = 15 episodes/hour; moderate sleep apnea (moderate, n = 460) with AHI > 15 and < or = 30 episodes/hour and severe sleep apnea (severe, n = 1178) with AHI > 30 episodes/hour. Daytime blood pressure measurements were performed under standardized conditions in each patient at 10 a.m. in office on the day of referring to sleep centers for getting average value. All the patients were requested to quit medications related to blood pressure for three days before the day of assessing.
RESULTSBoth daytime systolic blood pressure and diastolic blood pressure values were significantly related to AHI positively (r = 0.201 and 0.276, respectively; both P values < 0.001) and to nadir nocturnal oxygen saturation negatively (r = -0.215 and -0.277, respectively; both P values < 0.001), which were the parameters of OSA severity. In two special designed mean plots, means of daytime systolic and diastolic blood pressure increased gradually with increasing AHI. Beyond AHI of 61 - 65, this increasing trend reached a plateau.
CONCLUSIONSThe results showed that OSA severity was associated with daytime blood pressure until AHI of 61 - 65, providing evidence for early OSA management, especially in OSA patients with concomitant hypertension.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Pressure ; physiology ; China ; Female ; Humans ; Male ; Middle Aged ; Sleep Apnea, Obstructive ; pathology ; Young Adult

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