ABSTRACT
Background@#Developmental hypothyroidism impairs learning and memory in offspring, which depend on extensive neuronal circuits in the entorhinal cortex, together with the hippocampus and neocortex. The entorhinal-dentate gyrus pathway is the main entrance of memory circuits. We investigated whether developmental hypothyroidism impaired the morphological development of the entorhinal-dentate gyrus pathway. @*Methods@#We examined the structure and function of the entorhinal-dentate gyrus pathway in response to developmental hypothyroidism induced using 2-mercapto-1-methylimidazole. @*Results@#1,1´-Dioctadecyl-3,3,3´,3´-tetramethylindocarbocyanine perchlorate tract tracing indicated that entorhinal axons showed delayed growth in reaching the outer molecular layer of the dentate gyrus at postnatal days 2 and 4 in hypothyroid conditions. The proportion of fibers in the outer molecular layer was significantly smaller in the hypothyroid group than in the euthyroid group at postnatal day 4. At postnatal day 10, the pathway showed a layer-specific distribution in the outer molecular layer, similar to the euthyroid group. However, the projected area of entorhinal axons was smaller in the hypothyroid group than in the euthyroid group. An electrophysiological examination showed that hypothyroidism impaired the long-term potentiation of the perforant and the cornu ammonis 3–cornu ammonis 1 pathways. Many repulsive axon guidance molecules were involved in the formation of the entorhinaldentate gyrus pathway. The hypothyroid group had higher levels of erythropoietin-producing hepatocyte ligand A3 and semaphorin 3A than the euthyroid group. @*Conclusion@#We demonstrated that developmental hypothyroidism might influence the development of the entorhinal-dentate gyrus pathway, contributing to impaired long-term potentiation. These findings improve our understanding of neural mechanisms for memory function.
ABSTRACT
Objective To explore the correlation between EBV DNA load and peripheral immune cells (including lymphocyte supsets and natural killer cells) before treatment in patients with NPC, and analyze the influence of circulating immune cell supsets related to EBV on the prognosis of NPC patients. Methods We retrospectively analyzed the general data of 203 NPC patients without distant metastasis at the first treatment, as well as the data of peripheral blood EBV DNA and circulating immune cell supset. The ROC curve analysis was used to determine the cutoff value of each circulating immune cell supset. Kaplan-Meier method was used for survival analysis, and Cox regression model was used for multi-factor prognostic correlation analysis. Results The 3-year OS, PFS, DMFS and LRFS of EBV DNA < 400 copies/ml group and EBV DNA≥400 copies/ml group were 99.2% vs. 90.1% (P=0.001), 96.7% vs. 90.1% (P=0.028), 98.4% vs. 90.1% (P=0.005) and 98.4% vs. 100% (P > 0.05), respectively. EBV DNA is negatively correlated with the ratio of CD19+ B cells before treatment (r=-0.138, P=0.040), and there was no significant correlation between EBV DNA and other circulating immune supgroups (P > 0.05). ROC analysis showed that the cut-off value of CD19+B cell ratio before treatment related to the 3-year OS was 8.33% (P=0.02). The 3-year OS, PFS, DMFS and LRFS of patients with CD19+B cells ratio ≤8.33% and CD19+B cells ratio > 8.33% were respectively 90.4% vs. 99.2% (P=0.003), 89.2% vs. 97.5% (P=0.008), 90.4% vs. 98.3% (P=0.008) and 98.8% vs. 99.2% (P > 0.05). However, ROC analysis showed that there was no significant correlation between OS and other peripheral immune cells (including the proportion of CD3+T, CD3+CD4+T, CD3+CD8+T and CD56+NK cells and CD4+/CD8+ ratio). Multivariate analysis showed that EBV DNA load was an independent prognostic factor of 3-year PFS of NPC patients, and the ratio of CD19+B cells was an independent prognostic factor of 3-year PFS, MFS and OS of NPC patients. Conclusion Before treatment, there is a negative correlation between plasma EBV DNA and the proportion of CD19+B cells in peripheral blood. Both can be used as the predictors of 3-year OS, PFS and DMFS of NPC patients.
ABSTRACT
Objective To investigate the clinical outcomes of patients with locally advanced uterine cervical cancer (UCC) treated by 3-dimensional high dose rate-intracavitary brachytherapy (3D HDR-ICBT) combined with complementary applicator-guided external beam radiotherapy (EBRT).Methods A total of 120 patients pathologically diagnosed with locally advanced UCC (tumors with a maximum diameter≥6 cm or ≥5 cm complicated with eccentric tumor growth) treated with concurrent chemoradiotherapy (CCRT) from June 2010 to June 2015 were recruited.Five fractions of 3D HDR-ICBT combined with complementary applicator-guided external beam radiotherapy were performed.The prescribed dose for HR-CTV and IR-CTV was 7 Gy (D9o) and 5-6 Gy (D90).The rectum,sigmoid colon,bladder and adjacent small intestine were delineated as the organs at risk.Intensity-modulated radiation therapy (IMRT) was used for EBRT (45 Gy/ 25f) combined with cisplatin-based chemotherapy every three weeks (75 mg/m2).Results The median follow-up time was 46 months (14-96 months).The 5-year local control rate (LCR),disease-free survival (DFS),and overall survival (OS) were 92.8％,76.6％ and 81.0％,respectively.The incidence rate of grade Ⅰ-Ⅱ genitourinary and gastrointestinal acute toxicities were 57.8％ and 14.6％,whereas 8.1％ and 2.9％ for grade Ⅲ toxicities.The incidence rate of later grade Ⅰ-Ⅱ genitourinary and gastrointestinal toxicities were 8.4％ and 5.3％,and 0.97％ and 1.3％ for grade Ⅲ late toxicities.Conclusions The combination of HDR-ICBT with an applicator-guided IMRT (ICBT+IMRT) yields low incidence of severe adverse events,relatively high LC and OS rate for locally advanced UCC.It is an efficacious comprehensive treatment of locally advanced bulky UCC.