Major depressive disorder is one of the most deleterious mental disorders with a high suicide rate,incidence and recurrence rate,which is manifested as continuous depression,retardation of thinking as well as loss of ...Major depressive disorder is one of the most deleterious mental disorders with a high suicide rate,incidence and recurrence rate,which is manifested as continuous depression,retardation of thinking as well as loss of appetite and sleep disturbances[1,2].展开更多
Aim YL-0919 is permitted by SFDA for clinical trial recently as a new drug for depression. Whether YL-0919 is a fast-onset antidepressant and the possible mechanism related to roTOR pathway will be investigated. Metho...Aim YL-0919 is permitted by SFDA for clinical trial recently as a new drug for depression. Whether YL-0919 is a fast-onset antidepressant and the possible mechanism related to roTOR pathway will be investigated. Methods Chronic unpredictable stress rat model was used to evaluate the fast-onset effect of YL-0919 through su- crose preference test and a series behavior test. Morphological, eletrophysiological and biochemical methods were used for measure the neurogenesis, synaptogenesis, LTP and molecules proteins related in mTOR pathways. Re- suits YL-0919 （i. g. for 5 d or 14 d）played faster onset effects of anxiolytic and antidepressant on novelty sup- pressed food test compared with fluoxetine. Repeated i. g YL-0919 or fluoxetine （7d） increase the hippocampal LTP, Fluoxetine showed the same effect at the 21day in living rats in vivo. Chronic YL-0919 treatment facilitated LTP in the hippocampus synapses more than fluoxetine treatment. Morphometric measurement and analysis showed that chronic YL-0919 administration decreased the length of the active zone and reduced the thickness of CA1 posts- ynaptic densities compared to the normal, but were elevated compared to the fluoxetine group. Furthermore, the ex- pression of hippocampal synaptogenesis was increased with chronic YL-0919 administration but reduced with chron- ic fluoxetine treatment. Chronic administration （5 days） of YL-0919 resulted in a significant antidepressant effect. The behavioral effects were associated with increases in hippocampal brain-derived neurotrophic factor, synapsin, and mammalian target of rapamycin. Interestingly, the specific inhibitor of roTOR rapamycin can reverse the fast- TST and FST and even in the protein expression. Conclusion onset antidepressant effect of YL-0919 on SPT, These findings are the first time to supply evidence for fast-onset antidepressant effect of YL-0919. Furthermore, these effects appear to be associated with increases in markers of hippocampal neurogenesis, synaptogenesis and e- ven roTOR protein expression, suggesting the roTOR pathway involving with the fast-onset of YL-0919.展开更多
AIM To determine the incidence and associated factors of new-onset diabetes after transplantation(NODAT) in a Portuguese central hospital. METHODS This single-center retrospective study involved consecutive adult nond...AIM To determine the incidence and associated factors of new-onset diabetes after transplantation(NODAT) in a Portuguese central hospital. METHODS This single-center retrospective study involved consecutive adult nondiabetic transplant recipients, who had undergone kidney transplantation between January 2012 and March 2016. NODAT was diagnosed according to the criteria of the American Diabetes Association. Data were collected from an institutional database of the Nephrology and Kidney Transplantation Department(Santa Maria Hospital, Lisbon, Portugal) and augmented with data of laboratorial parameters collected from the corresponding patient electronic medical records. Exclusion criteria were preexisting diabetes mellitus, missing information and follow-up period of less than 12 mo. Data on demographic and clinical characteristics as well as anthropometric and laboratorial parameters were also collected. Patients were divided into two groups: With and without NODAT-for statistical comparison.RESULTS A total of 156 patients received kidney transplantduring the study period, 125 of who were included in our analysis. NODAT was identified in 27.2% of the patients(n = 34; 53% female; mean age: 49.5 ± 10.8 years; median follow-up: 36.4 ± 2.5 mo). The incidence in the first year was 24.8%. The median time to diagnosis was 3.68 ± 5.7 mo after transplantation, and 76.5% of the patients developed NODAT in the first 3 mo. In the group that did not develop NODAT(n = 91), 47% were female, with mean age of 46.4 ± 13.5 years and median follow-up of 35.5 ± 1.6 mo. In the NODAT group, the pretransplant fasting plasma glucose(FPG) levels were significantly higher [101(96.1-105.7) mg/d L vs 92(91.4-95.8) mg/d L, P = 0.007] and pretransplant impaired fasting glucose(IFG) was significantly more frequent(51.5% vs 27.7%, P = 0.01). Higher pretransplant FPG levels and pretransplant IFG were found to be predictive risk factors for NODAT development [odds ratio(OR): 1.059, P = 0.003; OR: 2.772, P = 0.017, respectively]. CONCLUSION NODAT incidence was high in our renal transplant recipients, particularly in the first 3 mo posttransplant, and higher pretransplant FPG level and IFG were risk factors.展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos.82174010 and 81973512).
文摘Major depressive disorder is one of the most deleterious mental disorders with a high suicide rate,incidence and recurrence rate,which is manifested as continuous depression,retardation of thinking as well as loss of appetite and sleep disturbances[1,2].
文摘Aim YL-0919 is permitted by SFDA for clinical trial recently as a new drug for depression. Whether YL-0919 is a fast-onset antidepressant and the possible mechanism related to roTOR pathway will be investigated. Methods Chronic unpredictable stress rat model was used to evaluate the fast-onset effect of YL-0919 through su- crose preference test and a series behavior test. Morphological, eletrophysiological and biochemical methods were used for measure the neurogenesis, synaptogenesis, LTP and molecules proteins related in mTOR pathways. Re- suits YL-0919 （i. g. for 5 d or 14 d）played faster onset effects of anxiolytic and antidepressant on novelty sup- pressed food test compared with fluoxetine. Repeated i. g YL-0919 or fluoxetine （7d） increase the hippocampal LTP, Fluoxetine showed the same effect at the 21day in living rats in vivo. Chronic YL-0919 treatment facilitated LTP in the hippocampus synapses more than fluoxetine treatment. Morphometric measurement and analysis showed that chronic YL-0919 administration decreased the length of the active zone and reduced the thickness of CA1 posts- ynaptic densities compared to the normal, but were elevated compared to the fluoxetine group. Furthermore, the ex- pression of hippocampal synaptogenesis was increased with chronic YL-0919 administration but reduced with chron- ic fluoxetine treatment. Chronic administration （5 days） of YL-0919 resulted in a significant antidepressant effect. The behavioral effects were associated with increases in hippocampal brain-derived neurotrophic factor, synapsin, and mammalian target of rapamycin. Interestingly, the specific inhibitor of roTOR rapamycin can reverse the fast- TST and FST and even in the protein expression. Conclusion onset antidepressant effect of YL-0919 on SPT, These findings are the first time to supply evidence for fast-onset antidepressant effect of YL-0919. Furthermore, these effects appear to be associated with increases in markers of hippocampal neurogenesis, synaptogenesis and e- ven roTOR protein expression, suggesting the roTOR pathway involving with the fast-onset of YL-0919.
文摘AIM To determine the incidence and associated factors of new-onset diabetes after transplantation(NODAT) in a Portuguese central hospital. METHODS This single-center retrospective study involved consecutive adult nondiabetic transplant recipients, who had undergone kidney transplantation between January 2012 and March 2016. NODAT was diagnosed according to the criteria of the American Diabetes Association. Data were collected from an institutional database of the Nephrology and Kidney Transplantation Department(Santa Maria Hospital, Lisbon, Portugal) and augmented with data of laboratorial parameters collected from the corresponding patient electronic medical records. Exclusion criteria were preexisting diabetes mellitus, missing information and follow-up period of less than 12 mo. Data on demographic and clinical characteristics as well as anthropometric and laboratorial parameters were also collected. Patients were divided into two groups: With and without NODAT-for statistical comparison.RESULTS A total of 156 patients received kidney transplantduring the study period, 125 of who were included in our analysis. NODAT was identified in 27.2% of the patients(n = 34; 53% female; mean age: 49.5 ± 10.8 years; median follow-up: 36.4 ± 2.5 mo). The incidence in the first year was 24.8%. The median time to diagnosis was 3.68 ± 5.7 mo after transplantation, and 76.5% of the patients developed NODAT in the first 3 mo. In the group that did not develop NODAT(n = 91), 47% were female, with mean age of 46.4 ± 13.5 years and median follow-up of 35.5 ± 1.6 mo. In the NODAT group, the pretransplant fasting plasma glucose(FPG) levels were significantly higher [101(96.1-105.7) mg/d L vs 92(91.4-95.8) mg/d L, P = 0.007] and pretransplant impaired fasting glucose(IFG) was significantly more frequent(51.5% vs 27.7%, P = 0.01). Higher pretransplant FPG levels and pretransplant IFG were found to be predictive risk factors for NODAT development [odds ratio(OR): 1.059, P = 0.003; OR: 2.772, P = 0.017, respectively]. CONCLUSION NODAT incidence was high in our renal transplant recipients, particularly in the first 3 mo posttransplant, and higher pretransplant FPG level and IFG were risk factors.
