ABSTRACT
OBJECTIVE To study the role of phosphatidylinositol-3-kinase （PI3K） on sunitinib-induced myocardial systolic dysfunction. METHODS Using human-induced pluripotent stem cell-derived cardiomyocytes （hiPSC-CMS） as objects， the contractile force of cardiomyocytes was measured by CardioExcyte 96 system， and IC50 of sunitinib was calculated after hiPSC- CMS were treated with sunitinib at different concentrations [0 （control）， 0.5， 1， 3， 5， 10 μmol/L] for 24 hours. The effects of sunitinib （3.14 μmol/L） on the contractile frequency of cardiomyocytes， calcium transient amplitude and calcium transient recovery time course， mRNA expression of myocardial injury markers atrial natriuretic peptide （ANP）， brain natriuretic peptide （BNP） and β-myosin heavy chain （β-MHC） were detected. PI3K activator 3，4，5-triphosphate phos-phatidylinositol （PIP3， 1 μmol/L） and sunitinib were used to intervene in hiPSC-CMs jointly， so as to investigate the role of PI3K in the myocardial systolic dysfunction induced by sunitinib. RESULTS Sunitinib inhibited the contractile force of hiPSC-CMs in a concentration-dependent manner. IC50 of sunitinib was 3.14 μmol/L. After intervention with 3.14 μmol/L sunitinib， the contractile frequency of hiPSC-CMs and calcium transient amplitude were decreased significantly （P＜0.05 or P＜0.01）； the duration of calcium transient recovery was prolonged significantly （P＜0.05）， and mRNA expressions of ANP， BNP and β-MHC were significantly increased （P＜0.01）. After PI3K was activated with PIP3， the contractile force of hiPSC-CMs was increased significantly （P＜0.01）. CONCLUSIONS Activating PI3K activity is a potential molecular mechanism to improve myocardial toxicity induced by sunitinib.
ABSTRACT
Objective:To observe and analyze the multimodal imaging characteristics of fundus in patients with sympathetic ophthalmia (SO).Methods:A retrospective study. From October 2012 to December 2021, 28 patients (36 eyes) diagnosed SO in the Department of Ophthalmology, Beijing Tongren Hospital were inclued in the study. There were 19 males (25 eyes) and 9 females (11 eyes), with the mean age of 51.61±12.02 years. There were 8 exciting eyes and 28 sympathizing eyes. The time to onset after trauma or surgery was 46.10±107.98 months. All patients underwent examinations including vision test, color fundus photograph, optical coherence tomography (OCT), fundus fluorescence angiography (FFA), indocyanine green angiography (ICGA). Angio-OCT (OCTA) was performed on 3 eyes and fundus autofluorescence (AF) was performed on 8 eyes. The early and late phase were defined respectively as ≤2 months and >2 months. Their multimodal imaging characteristics were summarized.Results:In 8 exciting eyes, subretinal fibrosis with mutifocal retinal atrophy and pigmentation was noted in 5 eyes (62.50%, 5/8), the other 3 eyes showed sunset glow fundus (37.50%, 3/8). In 28 sympathizing eyes, in the early phase, the fundus photograph showed shallow retinal detachment with optic disc edema in 9 eyes (32.14%, 9/28); in the late phase, peripapillary yellowish-white subretinal lesions in 11 eyes (39.29%, 11/28). In the late course of the disease, there were yellow-white lesions around the optic disc (peridisc) and peripheral subretinal area in 11 eyes (39.29%, 11/28). Dalen-Fuchs nodules were found in 10 eyes (35.71%, 10/28). On OCT, multiple serous retinal detachment and irregular choroidal folds were noted in the early phase; hill-like subretinal hyperreflective elevation was noted in peripapillary area and subfovea with presence of cystic spaces in the intraretina in the late phase. FFA examination showed"pinpoint-like" strong fluorescence in the early stage, and "multi-lake-like" fluorescein accumulation and leakage in the late stage; "map-like" weak fluorescence around the disc in the early stage of the disease, dot-like strong fluorescence lesions in each quadrant of the peripheral retina, and fluorescence in the late stage of the disease course. enhanced. ICGA examination showed that the FFA strong fluorescence lesions in the middle and late stages were weak fluorescence. FAF examination, point-like strong and weak autofluorescence lesions with unclear boundaries. Nine sympathizing eyes with subretinal yellow-white lesions has vision without light-0.1 (significantly decreased vison), while 8 eyes with sunset glow fundus was 0.5-1.0 (mildly decreased vison).Conclusions:SO could not only show the semblable features of acute phases of Vogt-Koyanagi-Harada syndrome, but also the yellowish-white lesions in the peripapillary area, macula and periphery. Most of the eyes with peripapillary lesions has a significantly decreased vison, while the eyes with sunset glow fundus has a mildly decreased vison.