RESUMO
Microgliosis is a hallmark of many neurological diseases, including Alzheimer's disease, stroke, seizure, traumatic brain and spinal cord injuries, and peripheral and optic nerve injuries. Recent studies have shown that the newly self-renewed microglia have specific neurological functions. However, the mechanism of adult microglia proliferation remains largely unclear. Here, with single-cell RNA sequencing, flow cytometry, and immunohistochemistry, we demonstrate that the sciatic nerve injury induced two distinct phases of microglia proliferation in mouse spinal cord, each with different gene expression profiles. We demonstrate that the transcription factor Myc was transiently upregulated in spinal cord microglia after nerve injury to mediate an early phase microglia proliferation. On the other hand, we reveal that the tumor-necrosis factor alpha-induced protein 3 (Tnfaip3) was downregulated to mediate the Myc-independent late-phase microglia proliferation. We show that cyclin dependent kinase 1, a kinase with important function in the M phase of the cell cycle, was involved only in the early phase. We reveal that although the early phase was neither necessary nor sufficient for the late phase proliferation, the late-phase suppressed the early phase microglia proliferation in the spinal cord. Finally, we demonstrate that the termination of spinal cord microglia proliferation required both Myc and Tnfaip3 to resume their baseline expression. Thus, we have delineated an interactive signaling network in the proliferation of differentiated microglia.
RESUMO
OBJECTIVE: To determine impact of age and other prognostic factors on the survival of ovarian immature teratoma (IT) patients. METHODS: Data obtained from the SEER database between 1973 and 2012. Kaplan-Meier methods and multivariate Cox regression models were used for statistical analyses. RESULTS: Of 1307 patients (median: 24years; range: 0-93), 78%, 5%, 13%, 4% were stages I, II, III and IV, respectively. 25%, 35%, and 40% had grades 1, 2, and 3. Whites were less likely to be diagnosed, and Asians had a nearly 3-fold higher proportion of IT compared to the proportion of Asians in the U.S. census. The 5-year disease-specific survival (DSS) was 91.2%. Those with stages I, II, III and IV disease had survivals of 99.7%, 95%, 81%, and 71.8% (p<0.001) and grades 1, 2, and 3 had DSS of 98.7%, 95.8%, and 91% (p<0.001), respectively. Of those who underwent fertility-preserving surgery, the DSS was 98.8%. Over time from 1973 to 1986, to 1987-1999, to 2000-2012, the survivals were 76.4%, 92.8%, and 94.7% (p<0.001). Of stage I patients, no patient <18years (n=214, used as adult cutoff) and 2 of 283 patients >18years died of cancer, with corresponding 5years DSS of 100% vs. 99.6% (p>0.05). Older age (by year, HR: 1.05; 95% CI: 1.04-1.06; p<0.0001) and higher stage (HR: 11.52; 95% CI: 4.08-32.48; p<0.0001) were independent factors indicating poorer survival. CONCLUSION: The outcome of patients with stage I disease was excellent at 99.7%, with children and adults having corresponding survivals of 100% and 99.6%.