Comprehensive review of clinical presentation, diagnosis, management, and prognosis of ruptured hepatocellular carcinoma.

BACKGROUND: Spontaneous rupture of hepatocellular carcinoma (rHCC) is a life-threatening complication that occurs in 3 % to 15 % of patients with hepatocellular carcinoma (HCC). This review aimed to discuss the most recent updates in the epidemiology, pathophysiology, risk factors, diagnosis as well as presentation, management, and prognostic factors of rHCC. METHODS: A comprehensive systematic review was conducted using Medline/PubMed and Web of Science databases with the end of search date being December 1, 2023 regarding rHCC diagnosis, imaging, and management. RESULTS: Achieving adequate hemostasis and stabilization of the patient remains the primary objective in the management of patients with rHCC. In earlier studies, the mortality rate in the acute phase of rHCC was reported to be 25 % to 75 %. However, more recent studies have demonstrated that transcatheter arterial embolization (TAE)/transcatheter arterial chemoembolization (TACE) followed by elective hepatectomy in select patients may offer improved survival benefits and decrease perioperative complications compared with TAE/TACE alone or emergent/1-stage hepatectomy. CONCLUSION: Although the prognosis for rHCC remains the worst among causes of death related to HCC, more recent studies have demonstrated that improved short- and long-term patient outcomes may be achieved through active surveillance efforts for HCC combined with advanced multimodal diagnostic tools and multidisciplinary management strategies.

Recording γ-secretase activity in living mouse brains.

γ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Förster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of γ-secretase activity on a cell-by-cell basis in live neurons in culture . Nevertheless, how γ-secretase activity is regulated in vivo remains unclear. Here we employ the near-infrared (NIR) C99 720-670 biosensor and NIR confocal microscopy to quantitatively record γ-secretase activity in individual neurons in living mouse brains. Intriguingly, we uncovered that γ-secretase activity may influence the activity of γ-secretase in neighboring neurons, suggesting a potential "cell non-autonomous" regulation of γ-secretase in mouse brains. Given that γ-secretase plays critical roles in important biological events and various diseases, our new assay in vivo would become a new platform that enables dissecting the essential roles of γ-secretase in normal health and diseases.

Near-infrared fluorescence lifetime imaging of amyloid-ß aggregates and tau fibrils through the intact skull of mice.

Non-invasive methods for the in vivo detection of hallmarks of Alzheimer's disease can facilitate the study of the progression of the disease in mouse models and may enable its earlier diagnosis in humans. Here we show that the zwitterionic heptamethine fluorophore ZW800-1C, which has peak excitation and emission wavelengths in the near-infrared optical window, binds in vivo and at high contrast to amyloid-ß deposits and to neurofibrillary tangles, and allows for the microscopic imaging of amyloid-ß and tau aggregates through the intact skull of mice. In transgenic mouse models of Alzheimer's disease, we compare the performance of ZW800-1C with that of the two spectrally similar heptamethine fluorophores ZW800-1A and indocyanine green, and show that ZW800-1C undergoes a longer fluorescence-lifetime shift when bound to amyloid-ß and tau aggregates than when circulating in blood vessels. ZW800-1C may prove advantageous for tracking the proteinic aggregates in rodent models of amyloid-ß and tau pathologies.