1.Real-time platelet P2Y12 receptor occupancy as a promising pharmacodynamics biomarker for bridging the gap between PK/PD of clopidogrel therapy.
Haipeng LI ; Yueming GU ; Yumeng ZHAO ; Aiyun XU ; Dong SUN ; Jingkai GU
Acta Pharmaceutica Sinica B 2025;15(1):484-493
Clopidogrel effectively inhibits platelet aggregation in response to ADP by irreversibly binding to the platelet P2Y12 receptor through its active metabolite. However, the observed discrepancies between the pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel present substantial challenges in individualizing of antiplatelet therapy. To address these challenges, a robust liquid chromatography-tandem mass spectrometry method has been developed to facilitate the real-time assessment of platelet P2Y12 receptor occupancy. This method has been validated in animal models, providing a reliable link between individual PK profiles and PD effects. Target receptor occupancy offers a comprehensive overview of interindividual variations in clopidogrel metabolism, regulation of P2Y12 receptor expression, and platelet turnover. Moreover, it directly correlates with the inhibitory effect on platelet aggregation. The levels of platelet P2Y12 occupancy accurately reflect the extent of clinical factors influencing the PD of clopidogrel, including dosage, drug-drug interactions (DDI), and type 2 diabetes mellitus (T2DM). As a normalized metric, platelet P2Y12 occupancy not only serves potential as a diagnostic tool for personalized clopidogrel therapy but also aids in elucidating the role of the P2Y12 signaling pathway in cases of abnormal on-treatment platelet reactivity.
2.Indoor air quality in classrooms of primary and secondary schools during autumn and winter in Hangzhou
YING Xiao, ZHU Lu, WU Yuzhen, GU Yueming, WU Guohua
Chinese Journal of School Health 2020;41(5):765-768
Objective:
To understand indoor air quality in middle and primary schools of Hangzhou in autumn and winter seasons, and to provide references of promoting indoor air quality of schools.
Methods:
Totally 33 classrooms of 11 schools in urban area were selected into study during Sept.2018 to Jan.2019. Daily measurements of PM2.5 and CO2 were performed in selected classes during school working time by air quality monitors. Totally, monitoring data of 35 964 hours were analyzed using univariate and multiplicity analysis for PM2.5 and CO2 level, variability and possible influence factors.
Results:
In autumn and winter, hourly average values of classroom PM2.5 and CO2 concentration level in Hangzhou were between 35.30 to 74.65 μg/m3 and between 949.17 to 2 029.98 mg/m3, respectively. The concentration levels of PM2.5 and CO2 were higher with the temperature(F=1 412.84, 775.66, P<0.01). No statistical significance was be found for the difference of PM2.5 concentration among monitoring times. Wave changes in CO2 were observed with time variation PM2.5 and CO2 concentration level of 68.42% monitoring times was complied with standards. School type and temperature correlated with PM2.5 concentration level. The PM2.5 concentration level in senior high school was higher than that in junior high school, while the value in primary school was the minimum(β=0.44, P<0.01). And the PM2.5 concentration increased with the temperature decreased(β=8.31, P<0.01). School type, temperature and monitoring time correlated with CO2 concentration level. CO2 concentration increased with the increase of grade, decrease in temperature and later time during the day(β=213.64, 162.38, P<0.01). The CO2 concentration level in later monitoring time was lower than that in earlier monitoring time(β=-16.28, P<0.01).
Conclusion
Classroom CO2 concentration level in Hangzhou was closed to that in European schools, while PM2.5 concentration level was much higher. Comparing with other cities in China, classroom PM2.5 and CO2 concentration level in Hangzhou is better. The results highlighted that school location, design and routine management should be advanced consideration for good air quality in classroom.
3.Clinical Significance and Functional Prediction of Up-regulated RAD21 in Lung Cancer
Xuejing GU ; Yueming WU ; Jing GAO
Journal of China Medical University 2016;45(4):328-332
Objective To detect the expression levels of RAD21(S.Pombe RAD21 homolog)in lung cancer,and assess its clinical significance and potential functions. Methods The expression level of RAD21 in lung cancer was determined by Western blot and immunohistochemistry meth?ods;the RAD21 mRNA expression in lung cancer was analyzed through Oncomine database;the relationship between the RAD21 expression levels and prognosis in patients with lung cancer was studied by Kaplan Meier curve;the RAD21 functions in lung cancer were predicted by using gene set enrichment analysis. Results Compared with adjacent normal tissue,the protein level of RAD21 in lung tissues were upregulated . The data from Oncomine database showed that RAD21 mRNA levels were significantly higher than the normal control groups in multiple lung cancer datasets(P<0.01);in addition,Kaplan?Meier survival curves showed that the RAD21 expression levels was correlated with the survival of patients with lung can?cer(P<0.05);gene set enrichment analysis indicated that RAD21 was mainly enriched in apoptotic signaling pathways and cell cycle regulation gene sets. Conclusion The downregulated RAD21 could be used as a biomarker to assess the prognosis of lung cancer patients. In addition, RAD21 may be involved in the regulation of cell cycle and apoptosis,which affects the development and progression of lung cancer.
4.Effects of Danhong on the serum levels of CD137, high-sensitivity C-reactive protein (hs-CRP) and homocysteine in patients with non-ST elevation acute myocardial infarction complicating metabolic syndrome
Yongjin YAN ; Haipeng DENG ; Zongfeng GUO ; Lingling LIU ; Yang LU ; Shiya WANG ; Shunzhong GU ; Hongsheng DING ; Yueming ZHANG ; Min PAN ; Jianhua ZHU ; Hualiang JI
International Journal of Traditional Chinese Medicine 2014;(12):1092-1095
Objective To investigate effects of Danhong on the serum levels of CD137, high-sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy) in patients with non-ST elevation acute myocardial infarction complicating metabolic syndrome. Methods A total of 126 patients with non-ST elevation acute myocardial infarction complicating metabolic syndrome were enrolled and randomly divided into a conventional treatment group and a Danhong treatment group using a random-digit table, with 63 patients in each group. All patients underwent angiography or percutaneous coronary intervention. The patients in the Danhong treatment group treated with intravenous Danhong 20 ml on the basis of conventional treatment for 1 week. The serum levels of CD137, hs-CRP and Hcy were measured at hospital admission and 10 days after treatment. The severity of coronary artery disease was assessed by the Gensini-score. Results The levels of CD137, hs-CRP and Hcy in both groups after treatment were significantly lower than before treatment (conventional treatment group: t 12.393, 17.408 and 9.458; Danhong treatment group: t 16.110, 17.573 and 13.481; all P<0.01), and the Danhong treatment group were significantly decreased than the conventional treatment group (t 2.815, 3.224 and 3.157, all P<0.01). The serum levels of CD137 and hs-CRP before treatment were significantly correlated with Gensini scores in 126 patients (r 0.720 and 0.562,all P<0.01). Conclusions The serum levels of CD137 and hs-CRP are significantly correlated with the severity of coronary artery disease, intravenous Danhong may has protective effect for coronary artery disease via decreasing CD137 and hs-CRP.


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