ABSTRACT
The master circadian clock generates 24-hour rhythms to orchestrate daily behavior, even running freely under constant conditions. Traditionally, the master clock is considered self-sufficient in sustaining free-running timekeeping via its cell-autonomous molecular clocks and interneuronal communications within the circadian neural network. Here, we find a set of bona fide ultradian oscillators in the Drosophila brain that support free-running timekeeping, despite being located outside the master clock circuit and lacking clock gene expression. These extra-clock electrical oscillators (xCEOs) generate cell-autonomous ultradian bursts, pacing widespread burst firing and promoting rhythmic resting membrane potentials in clock neurons via parallel monosynaptic connections. Silencing xCEOs disrupts daily electrical rhythms in clock neurons and impairs cycling of neuropeptide pigment dispersing factor, leading to the loss of free-running locomotor rhythms. Together, we conclude that the master clock is not self-sufficient to sustain free-running behavior rhythms but requires additional endogenous inputs to the clock from the extra-clock ultradian brain oscillators.
ABSTRACT
Postoperative intravesical instillation of chemotherapy is a routine procedure for non-muscular invasive bladder cancer (NMIBC). However, traditional bladder perfusion methods have insufficient exposure time, resulting in unsatisfactory therapeutic effects. In the present study, a chitosan (CS)-based in situ forming depot (ISFD) delivery system, including Fe3O4 magnetic nanoparticles (Fe3O4-MNP), CS, and ß-glycerophosphate (GP) as main components, was synthesized. Pirarubicin (THP), as a chemotherapeutic drug, was loaded into the new system. Results showed that our carrier system (Fe3O4-THP-CS/GP) was converted into gel and attached to the bladder wall, possessing loose network structures with magnetic targeting and sustained release properties. Moreover, its retention time in bladder was more than 72 h accompanied by a suitable expansion rate and good degradation characteristics. The antitumor activities of Fe3O4-THP-CS/GP were more effective both in vitro and in vivo than the free THP solution. In the study of its mechanism, results showed that Fe3O4-THP-CS/GP suppressed the expression of occludin (OCLN) and affected tight junctions (TJ) between urothelial cells to promote THP absorption.
ABSTRACT
BACKGROUND: This is an exploratory research of cystoprostatectomy (CP) in treating prostate cancer (PCa) extending to the bladder, which aimed to evaluate the effects of CP on survival outcomes and improving quality of life (QoL) in these patients. METHODS: A total of 27 PCa patients extending to the bladder were subjected to CP and followed up at regular intervals in our center. Prostate cancer-specific survival (PCSS) and prostate-specific antigen recurrence-free survival (PFS) were assessed by Kaplan-Meier analysis. Multivariate Cox regression was performed to evaluate clinical characteristics predicting survivals. QoL and pelvic symptoms were also evaluated. RESULTS: Median PCSS was not reached over the period of follow-up. 5-year PCSS rate was 82.1%. Median PFS was 66.0 months. 5-year PFS rate was 58.5%. Multivariate analysis showed Gleason score (≥ 8) (hazard ratio (HR) 2.55, 95% confidence interval (CI) 1.28-4.04, p = 0.033), positive local lymph node status (HR 3.52, 95% CI 1.57-7.38, p = 0.006) and bladder muscle-invasion (HR 4.75, 95% CI 1.37-7.53, p < 0.001) were independent predictors of worse PCSS. The number of patients suffering pelvic symptoms was significantly decreased, and QoL scores were significantly down-regulated after surgeries. CONCLUSION: CP offered effective and durable palliation in patients of locally advanced prostate cancer with invasion of the bladder, providing better QoL and relieving local symptoms.
Subject(s)
Prostatic Neoplasms , Quality of Life , Humans , Male , Neoplasm Recurrence, Local , Prostatectomy , Prostatic Neoplasms/pathology , Retrospective Studies , Urinary Bladder/pathologyABSTRACT
Bladder neck contracture (BNC), one of the most challenging complications after transurethral resection of the prostate (TURP) and photoselective vaporization of the prostate (PVP), lacks effective treatment. In the present study, our experience in treating BNC using GreenLight laser vaporization with triamcinolone acetonide (TA) injections was shared. This is a retrospective cohort study that included 46 patients with BNC after TURP and PVP in our center. GreenLight laser surgeries (180 W) were carried out and TA was administrated simultaneously. TA injections were repeated every week for three times after surgeries. The perioperative and postoperative parameters were reviewed and compared. Bladder neck tissues were examined by immunohistochemical staining to explore the expressions of collagen I, matrix metalloproteinase-3 (MMP-3), and transforming growth factor-ß (TGF-ß) after treatments. The chief complaint symptoms of all patients were significantly relieved after our treatments. None of them showed BNC recurrence during the follow-up. Complications were rare and mild. Postoperative assessments including maximal urinary flow rate (P < 0.01), International Prostate Symptom Score (P < 0.01), quality of life index (P < 0.01), and post-void residual volume (P < 0.001) were significantly better than baseline values, respectively. Immunohistochemical staining showed significantly lower expressions of collagen I (P < 0.001), MMP-3 (P < 0.001), and TGF-ß (P < 0.001) after treatments. In conclusion, 180-W GreenLight laser with repeated TA injections demonstrated the safety and long-term efficacy in treating BNC, by inhibiting the expressions of fibrotic factors. Our procedure was a promising treatment for BNC after PVP and TURP.
