BackgroundBone is a preferential site for prostate cancer (PCa) metastasis. However, sites of synchronous distant metastases in PCa patients with bone metastases at initial diagnosis and their impacts on prognosis are still unclear, limiting our ability to better stratify and treat the patients. In this study, we examined the sites of synchronous extra‐skeletal metastases in de novo PCa patients with bone metastases and their associated prognoses. MethodsIn total, 16,643 de novo PCa patients with bone metastases from the SEER database were included. After stratification of metastatic sites (bone, lung, liver, and brain) and treatment modalities, overall survival (OS) and independent predictors of OS, were analyzed. ResultsLung was the most frequent site of synchronous metastases, followed by liver, while brain metastases were relatively uncommon. Patients with bone‐only metastases showed the longest mean survival time (35.87 months, p < 0.001), followed by patients with bone and lung metastases (30.74 months, p < 0.001). Patients with bone and liver metastases had the shortest mean survival time (17.39 months, p < 0.001). Age > 70 years, unmarried status, high tumor grade, prostate‐specific antigen (PSA) > 50 ng/ml, and Gleason score ≥ 8 were associated with poor OS (all p < 0.01). Asian or Pacific Islander ethnic background was associated with a favorable OS (all p < 0.01). Chemotherapy improved OS in patients without brain metastases (all p < 0.05). For patients with bone‐only metastases, radical prostatectomy (RP) (HR, 0.339; 95% CI 0.231–0.495; p < 0.001), brachytherapy (BT) (HR, 0.567; 95% CI 0.388–0.829; p = 0.003), and chemotherapy (HR, 0.850; 95% CI 0.781–0.924; p < 0.001) were associated with prolonged OS. ConclusionsAge, race, tumor grade, PSA, Gleason score, sites of synchronous extra‐skeletal metastases, as well as treatment modalities affected OS in newly diagnosed PCa patients with bone metastases. Synchronous liver metastases were associated with poor OS. Chemotherapy improved OS in patients without brain metastases. RP and BT improved OS in patients with bone‐only metastases. Further investigation is warranted to validate these findings.

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Background: Neoadjuvant radiotherapy (RT) has been shown to improve local control; however, whether it can improve overall survival (OS) in locally advanced rectal cancer (LARC) patients remains controversial. We therefore aimed to examine the benefits of surgery alone, neoadjuvant radiotherapy (RT), adjuvant RT, and surgery plus chemotherapy in stage II (T3/4N0M0) and III (any T and N + M0) on the OS of rectal cancer patients. Methods: Date from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2004 and 2016 were used. Kaplan-Meier analyses were used to compare patient prognoses across different treatment modalities. Cox hazard regression analysis were used to identify independent predictors of OS. Results: For stage T3/4N0M0 patients, neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy resulted in similar OS (all p > 0.05; mean survival, 115.89 months (M), 111.97 M, and 117.22 M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p < 0.001, mean survival, 88.96 M). For stage T1/2N + M0 patients, neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy resulted in similar OS (all p > 0.05; mean survival, 121.50 M, 124.25 M, and 121.20 M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p < 0.001, mean survival 83.81 M). For stage T3/4N + M0 patients, neoadjuvant RT (HR = 0.436; 95% CI, 0.396~0.478; p < 0.001) resulted in significantly longer OS than adjuvant RT and surgery plus chemotherapy (mean survival, 104.47 M, 93.94 M, and 93.62 M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p < 0.001, mean survival 54.87 M). Older age (> 60 years), black race, unmarried status, high tumour grade, and tumour size > 5 cm were all associated with a poor prognosis (all p < 0.05). Conclusions: Neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy results in better OS than surgery alone in LARC patients. Neoadjuvant RT has the potential to be highly recommended over adjuvant RT and surgery plus chemotherapy for T3/4N + M0 patients; however, it showed no OS advantage over adjuvant RT or surgery plus chemotherapy for T3/4N0M0 and T1/2N + M0 patients.

Background:Z-guggulsterone, an active compound extracted from the gum resin of the tree Commiphora mukul, has been shown to improve animal memory deficits via activating the brain-derived neurotrophic factor signaling pathway. Here, we investigated the antidepressant-like effect of Z-guggulsterone in a chronic unpredictable stress mouse model of depression.Methods:The effects of Z-guggulsterone were assessed in mice with the tail suspension test and forced swimming test. Z-guggulsterone was also investigated in the chronic unpredictable stress model of depression with fluoxetine as the positive control. Changes in hippocampal neurogenesis as well as the brain-derived neurotrophic factor signaling pathway after chronic unpredictable stress/Z-guggulsterone treatment were investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressant-like mechanisms of Z-guggulsterone.Results:Z-guggulsterone (10, 30 mg/kg) administration protected the mice against the chronic unpredictable stress-induced increases in the immobile time in the tail suspension test and forced swimming test and also reversed the reduction in sucrose intake in sucrose preference experiment. Z-guggulsterone (10, 30 mg/kg) administration prevented the reductions in brain-derived neurotrophic factor protein expression levels as well as the phosphorylation levels of cAMP response element binding protein, extracellular signal-regulated kinase 1/2, and protein kinase B in the hippocampus and cortex induced by chronic unpredictable stress. Z-guggulsterone (10, 30 mg/kg) treatment also improved hippocampal neurogenesis in chronic unpredictable stress-treated mice. Blockade of the brain-derived neurotrophic factor signal, but not the monoaminergic system, attenuated the antidepressant-like effects of Z-guggulsterone.Conclusions:Z-guggulsterone exhibits antidepressant activity via activation of the brain-derived neurotrophic factor signaling pathway and upregulation of hippocampal neurogenesis.