RESUMO
Tumor metabolic reprogramming is a hallmark of cancer development, and targeting metabolic vulnerabilities has been proven to be an effective approach for castration-resistant prostate cancer (CRPC) treatment. Nevertheless, treatment failure inevitably occurs, largely due to cellular heterogeneity, which cannot be deciphered by traditional bulk sequencing techniques. By employing computational pipelines for single-cell RNA sequencing, we demonstrated that epithelial cells within the prostate are more metabolically active and plastic than stromal cells. Moreover, we identified that neuroendocrine (NE) cells tend to have high metabolic rates, which might explain the high demand for nutrients and energy exhibited by neuroendocrine prostate cancer (NEPC), one of the most lethal variants of prostate cancer (PCa). Additionally, we demonstrated through computational and experimental approaches that variation in mitochondrial activity is the greatest contributor to metabolic heterogeneity among both tumor cells and nontumor cells. These results establish a detailed metabolic landscape of PCa, highlight a potential mechanism of disease progression, and emphasize the importance of future studies on tumor heterogeneity and the tumor microenvironment from a metabolic perspective.
RESUMO
BACKGROUND AND PURPOSE: Stereoscopic imaging systems have improved the surgical accuracy and patient safety but have induced unwanted visual disturbance, nausea, and ocular symptoms simultaneously. We measured and compared visual discomfort and visual fatigue induced by three-dimensional (3D) surgical imaging system and two-dimentional (2D) surgical imaging system, respectively. METHODS: This study compared ocular symptoms and visual functions immediately after four laparoscopic tasks including pick beans, paper cut, pass the curved needle, and knot tying. Ten participants started with 3D laparoscopy, 9 participants with 2D laparoscopy on the first day, and reversed the laparoscopy for the participants on the second day. Before performing the tasks and immediately after performing the tasks for 1 hour, the participants underwent an interview with questions on ocular symptoms, and then received the systematic measurements of the visual functions objectively. The ocular symptoms were compared between the two groups, and the visual functions were compared in each group and between the two groups. RESULTS: When comparing the 3D laparoscopy group with the 2D laparoscopy group, symptom scores showed statistically significant differences in blurred vision during the task (z=-3.64, P=0.00), irritated or burning eyes (z=-2.17, P=0.03), dry eyes (z=-2.72, P=0.01), eyestrain (z=-3.11, P=0.00), headache (z=-3.20, P=0.00), discomfort in eyes (z=-3.74, P=0.00). The objective visual functional parameters such as distance exophoria (P=0.83), near exophoria (P=0.88), distance esophoria (P=0.93), near esophoria (P=0.80), the fusion range (P=0.09), the accommodative convergence/accommodation (P=0.56), and the tear film breakup time (P=0.48) had no significant difference between the two groups. CONCLUSIONS: When the passively polarized 3D surgical imaging system was compared with the 2D surgical imaging system, although subjective feelings were uncomfortable, there was no objective evidence to indicate that the 3D surgical imaging system resulted in an increment of visual fatigue. The visual fatigue and discomforts were moderate and could be tolerated by the surgeons.
