1.Imaging poly(ADP-ribose) polymerase-1 (PARP1) in vivo with 18F-labeled brain penetrant positron emission tomography (PET) ligand.
Xin ZHOU ; Jiahui CHEN ; Jimmy S PATEL ; Wenqing RAN ; Yinlong LI ; Richard S VAN ; Mostafa M H IBRAHIM ; Chunyu ZHAO ; Yabiao GAO ; Jian RONG ; Ahmad F CHAUDHARY ; Guocong LI ; Junqi HU ; April T DAVENPORT ; James B DAUNAIS ; Yihan SHAO ; Chongzhao RAN ; Thomas L COLLIER ; Achi HAIDER ; David M SCHUSTER ; Allan I LEVEY ; Lu WANG ; Gabriel CORFAS ; Steven H LIANG
Acta Pharmaceutica Sinica B 2025;15(10):5036-5049
Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its 18F-isotopologue ([18F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [18F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [18F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.
2.Clinical characteristics of sepsis-associated acute kidney injury: a retrospective analysis of 197 cases
Yirui GAO ; Qiang LI ; Ruifeng ZENG ; Suyi YANG ; Guocong CHEN ; Jun LI
Chinese Journal of Emergency Medicine 2022;31(10):1368-1372
Objective:To retrospectively analyze the incidence, mortality, clinical characteristics and related factors of transient and persistent acute kidney injury in patients with sepsis in emergency department.Methods:Patients with sepsis ≥ 18 years old hospitalized in the Emergency Department of Guangdong Provincial Hospital of Chinese Medicine from June 2018 to May 2020 were selected as the research objects. According to the renal function injury at admission and the renal function recovery at 48 h after admission, patients with sepsis were divided into three groups: non-S-AKI group, transient S-AKI group, and persistent S-AKI group.Results:A total of 197 patients with sepsis were included, including 95 patients with non-S-AKI, 39 patients with transient S-AKI and 63 patients with persistent S-AKI. The mortality in the persistent S-AKI group was significantly higher than that in the non-S-AKI group (36.5% vs. 17.9%, P<0.05), but there was no significant difference between the transient S-AKI group and non-S-AKI group (20.5% vs. 17.9%, P>0.05). Multiple categorical disordered Logistic regression analysis showed that urea was associated with transient S-AKI ( OR=1.440, 95% CI: 1.235-1.680), and age ( OR=1.049, 95% CI: 1.008-1.092), urea ( OR=1.440, 95% CI: 1.277-1.733), and infection site in non-urinary tract ( OR=0.149, 95% CI: 0.050-0.448) were associated with persistent S-AKI. Conclusions:The incidence of persistent S-AKI is higher than that of transient S-AKI. Persistent S-AKI is related to the prognosis of patients with sepsis, and the mortality rate is higher, while transient S-AKI has no significant relationship. The urea of patients with S-AKI would increase significantly, and advanced age and urinary tract infection are related factors for the occurrence of persistent S-AKI. For patients with sepsis with such factors, attention should be paid to early protection of renal function to prevent persistent S-AKI.
3.Effect of SKy bone expander system by percutaneous osteoplasty in treatment calcaneal fracture
Haitao CHEN ; Chaohua YANG ; Qunying LIANG ; Qizhong LI ; Haiou GUO ; Guocong DU ; Jiexiong OU
Chinese Journal of Primary Medicine and Pharmacy 2013;20(14):2092-2094
Objective To explore the clinical effect of percutaneous osteoplasty with SKy bone expander system in the treatment of calcaneal fracture.Methods 63 feet of 55 patients with calcaneal fractures were involved in this study.According to Sanders fracture classification including 38 feet of Sanders Ⅱ,18 feet of Sanders Ⅲ,7 feet of Sanders Ⅳ.There were 6 to 16 days interval between the injuries and the surgeries.The patients were treated by percutaneous osteoplasty with the SKy bone expander system.The standard of operation was the satisfaction of reduction and Bohler's and Gissane's angles under X-ray.Results All of 63 feet of 55 patients were followed up for average 22 months.According to the criterion of therapeutic effect,the results were as follows:excellent in 30 cases,good in 26 cases,fair in 7cases,and no poor case.The excellent and good rate was 88.9%.Conclusion Percutaneous osteoplasty with SKy bone expander system in the treatment of calcaneal fracture,especially in reduction and fixation of Sanders type Ⅱ and Sanders type Ⅲ,can recover Bohler's and Gissane's angles,significantly shorten the duration of illness,and has fast recovery and can possess satisfactory curative effect,and it is worth popularizing.

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