Background: Prostate cancer (PCa) is one of the most prevalent cancers that occur in men worldwide. Autophagy-related genes (ARGs) may play an essential role in multiple biological processes of prostate cancer. However, ARGs expression signature has rarely been used to investigate the association between autophagy and prognosis in PCa. This study aimed to identify and assess prognostic ARGs signature to predict overall survival (OS) and disease-free survival (DFS) in PCa patients. Methods: First, a total of 234 autophagy-related genes were obtained from The Human Autophagy Database. Then, differentially expressed ARGs were identified in prostate cancer patients based on The Cancer Genome Atlas (TCGA) database. The univariate and multivariate Cox regression analysis was performed to screen hub prognostic ARGs for overall survival and disease-free survival, and the prognostic model was constructed. Finally, the correlation between the prognostic model and clinicopathological parameters was further analyzed, including age, T status, N status, and Gleason score. Results: The OS-related prognostic model was constructed based on the five ARGs (FAM215A, FDD, MYC, RHEB, and ATG16L1) and significantly stratified prostate cancer patients into high- and low-risk groups in terms of OS (HR = 6.391, 95% CI = 1.581– 25.840, P < 0.001). The area under the receiver operating characteristic curve (AUC) of the prediction model was 0.84. The OS-related prediction model values were higher in T3-4 than in T1-2 (P = 0.008), and higher in Gleason score > 7 than ≤ 7 (P = 0.015). In addition, the DFS-related prognostic model was constructed based on the 22 ARGs (ULK2, NLRC4, MAPK1, ATG4D, MAPK3, ATG2A, ATG9B, FOXO1, PTEN, HDAC6, PRKN, HSPB8, P4HB, MAP2K7, MTOR, RHEB, TSC1, BIRC5, RGS19, RAB24, PTK6, and NRG2), with AUC of 0.85 (HR = 7.407, 95% CI = 4.850–11.320, P < 0.001), which were firmly related to T status (P < 0.001), N status (P = 0.001), and Gleason score (P < 0.001). Conclusions: Our ARGs based prediction models are a reliable prognostic and predictive tool for overall survival and disease-free survival in prostate cancer patients.

Apolipoprotein E (ApoE), encoded by the ApoE gene (APOE), influences the outcomes of traumatic brain injury (TBI), but the mechanism remains unclear. The present study aimed to investigate the effects of different ApoEs on the outcome of TBI and to explore the possible mechanisms. Controlled cortical impact (CCI) was performed on APOEε3 (E3) and APOEε4 (E4) transgenic mice, APOE-KO (KO) mice, and wild type (WT) mice to construct an in vivo TBI model. Neurological deficits, blood brain barrier (BBB) permeability and brain edema were detected at days 1, 3, and 7 after TBI. The results revealed no significant differences among the four groups at day 1 or day 3 after injury, but more severe deficits were found in E4 and KO mice than in E3 and WT mice. Furthermore, a significant loss of tight junction proteins was observed in E4 and KO mice compared with E3 and WT mice at day 7. Additionally, more expression and activation of NF-κB and MMP-9 were found in E4 mice compared with E3 mice. Different ApoEs had distinct effects on neuro-function and BBB integrity after TBI. ApoE3, but not E4, might inhibit the NF-κB/MMP-9 pathway to alleviate BBB disruption and improve TBI outcomes.

Traumatic brain injury (TBI) destroys white matter, and this destruction is aggravated by secondary neuroinflammatory reactions. Although white matter injury (WMI) is strongly correlated with poor neurological function, understanding of white matter integrity maintenance is limited, and no available therapies can effectively protect white matter. One candidate approach that may fulfill this goal is cannabinoid receptor 2 (CB2) agonist treatment. Here, we confirmed that a selective CB2 agonist, JWH133, protected white matter after TBI. The motor evoked potentials (MEPs), open field test, and Morris water maze test were used to assess neurobehavioral outcomes. Brain tissue loss, WM damage, Endoplasmic reticulum stress (ER stress), microglia responses were evaluated after TBI. The functional integrity of WM was measured by diffusion tensor imaging (DTI) and transmission electron microscopy (TEM). Primary microglia and oligodendrocyte cocultures were used for additional mechanistic studies. JWH133 increased myelin basic protein (MBP) and neurofilament heavy chain (NF200) levels and anatomic preservation of myelinated axons revealed by DTI and TEM. JWH133 also increased the numbers of oligodendrocyte precursor cells and mature oligodendrocytes. Furthermore, JWH133 drove microglial polarization toward the protective M2 phenotype and modulated the redistribution of microglia in the striatum. Further investigation of the underlying mechanism revealed that JWH133 downregulated phosphorylation of the protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (PERK) signaling pathway and its downstream signals eukaryotic translation initiation factor 2 α (eIF2α), activating transcription factor 4 (ATF4) and Growth arrest and DNA damage-inducible protein (GADD34); this downregulation was followed by p-Protein kinase B(p-Akt) upregulation. In primary cocultures of microglia and oligodendrocytes, JWH133 decreased phosphorylated PERK expression in microglia stimulated with tunicamycin and facilitated oligodendrocyte survival. These data reveal that JWH133 ultimately alleviates WMI and improves neurological behavior following TBI. However, these effects were prevented by SR144528, a selective CB2 antagonist. This work illustrates the PERK-mediated interaction between microglia and oligodendrocytes. In addition, the results are consistent with recent findings that microglial polarization switching accelerates WMI, highlighting a previously unexplored role for CB2 agonists. Thus, CB2 agonists are potential therapeutic agents for TBI and other neurological conditions involving white matter destruction.

A retrospective cohort study was conducted at the Children’s Hospital of Chongqing Medical University from November 2004 to December 2020 to investigate the long-term follow-up results after testicular torsion (TT) in children. Boys with TT were divided into the salvage orchiopexy group and the orchiectomy group, and the baseline characteristics, ultrasonographic indications, intraoperative findings, testicular volumes, and adverse events during follow-up were compared. A total of 145 cases were included in this study. Approximately 56.6% of patients who underwent salvage orchiopexy had testicular atrophy (TA), and the median testicular volume loss of the testes was 57.4%. Age less than 6 years, delayed surgery, and intraoperative poor blood supply were associated with TA in pediatric TT after orchiopexy. Most atrophied testes appeared within 3–6 months after surgery. Compared with the corresponding age-matched healthy controls, the contralateral testicular volumes were larger in the orchiopexy (P = 0.001 without TA, and P = 0.042 with TA) and orchiectomy groups (P = 0.033). The adverse events were comparable in patients with orchiectomy or orchiopexy. In summary, follow-up before 3 months after surgery may not offer sufficient clinical value, while that 3 months after surgery should be regarded as the first follow-up time for testicular monitoring. The contralateral testes of patients with TT showed compensatory hypertrophy. We suggest performing orchiectomy when torsed testes are surgically assessed as Arda grade III or inviable.