Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Objective: To construct a prediction model for preterm birth risk among pregnant women, so as to provide the reference for screening high-risk population and preventing preterm birth. Methods: Pregnant women who received antenatal examination and delivered at the Women's Hospital, School of Medicine, Zhejiang University from January 1 to December 31, 2019 were selected as the study subjects, among them, 80% were included in the modeling group, and 20% were included in the validation group. Demographic and clinical information were collected. A multivariable logistic regression model was used to analyze the predictive factors of preterm birth risk in the modeling group, and a preterm birth risk prediction model was established based on the OR values of predictive factors. The model was validated with the data from the validation group. The Youden index was used to determine the critical score for predicting preterm birth risk. The prediction performance of the model was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 15 197 pregnant women were surveyed, including 12 131 pregnant women in the observation group and 3 066 pregnant women in the validation group. There was no statistically significant difference in age, education level and gravidity between the two groups of pregnant women (all P<0.05). Multivariable logistic regression analysis identified the number of pregnancies, education level, place of residence, hypertension, diabetes, history of preterm birth, twin-pregnancy, placenta praevia, and gestational hypertension as risk prediction factors for preterm birth risk among pregnant women. The risk score system for preterm birth was established as follows: >2 pregnancies (2 points), high school education or below (4 points), college degree or above (-4 points), rural residence (5 points), hypertension (7 points), diabetes (11 points), history of preterm birth (11 points), twin-pregnancy (28 points), placenta previa (19 points), and gestational hypertension (12 points). The total score of the preterm birth risk scoring system ranged from -4 to 99 points. When the critical score was 8 points, the Youden index was the highest at 0.480, with an area under the ROC curve of 0.749 (95%CI: 0.732-0.767), a sensitivity of 0.610, and a specificity of 0.886, indicating good prediction performance of the model. Conclusion The preterm birth risk prediction model established in this study based on demographic and clinical characteristics of pregnant women can effectively predict the risk of preterm birth among pregnant women.

China's healthcare payment reform seeks to combine a medical insurance point-system with a global budget.The focus and difficulty in implementing the payment reform is how to make effectively link.On the basis of theoretical analysis,it selects the regions that have implemented the payment by disease under regional total budget and the payment by disease under institutional total budget,and summarizes the synergistic mechanism of total budget and payment by disease,including the strict control of total budget at the regional level,the reasonable setup of the budget or the standard of expected service volume at the institutional level,and the rate fluctuation and discount mechanism for the settlement of excess service;and further sort out the additional incentive mechanism to support innovation and quality enhancement under the background of the total budget and the payment by disease.Lessons can be drawn from the experiences of typical regions to strengthen the synergy between regional budgets,institutional budgets and payment by type of disease,and cautiously deal with the risks of excessive competition and"punching points"that may arise from the regional point method.

China's healthcare payment reform seeks to combine a medical insurance point-system with a global budget.The focus and difficulty in implementing the payment reform is how to make effectively link.On the basis of theoretical analysis,it selects the regions that have implemented the payment by disease under regional total budget and the payment by disease under institutional total budget,and summarizes the synergistic mechanism of total budget and payment by disease,including the strict control of total budget at the regional level,the reasonable setup of the budget or the standard of expected service volume at the institutional level,and the rate fluctuation and discount mechanism for the settlement of excess service;and further sort out the additional incentive mechanism to support innovation and quality enhancement under the background of the total budget and the payment by disease.Lessons can be drawn from the experiences of typical regions to strengthen the synergy between regional budgets,institutional budgets and payment by type of disease,and cautiously deal with the risks of excessive competition and"punching points"that may arise from the regional point method.

China's healthcare payment reform seeks to combine a medical insurance point-system with a global budget.The focus and difficulty in implementing the payment reform is how to make effectively link.On the basis of theoretical analysis,it selects the regions that have implemented the payment by disease under regional total budget and the payment by disease under institutional total budget,and summarizes the synergistic mechanism of total budget and payment by disease,including the strict control of total budget at the regional level,the reasonable setup of the budget or the standard of expected service volume at the institutional level,and the rate fluctuation and discount mechanism for the settlement of excess service;and further sort out the additional incentive mechanism to support innovation and quality enhancement under the background of the total budget and the payment by disease.Lessons can be drawn from the experiences of typical regions to strengthen the synergy between regional budgets,institutional budgets and payment by type of disease,and cautiously deal with the risks of excessive competition and"punching points"that may arise from the regional point method.

China's healthcare payment reform seeks to combine a medical insurance point-system with a global budget.The focus and difficulty in implementing the payment reform is how to make effectively link.On the basis of theoretical analysis,it selects the regions that have implemented the payment by disease under regional total budget and the payment by disease under institutional total budget,and summarizes the synergistic mechanism of total budget and payment by disease,including the strict control of total budget at the regional level,the reasonable setup of the budget or the standard of expected service volume at the institutional level,and the rate fluctuation and discount mechanism for the settlement of excess service;and further sort out the additional incentive mechanism to support innovation and quality enhancement under the background of the total budget and the payment by disease.Lessons can be drawn from the experiences of typical regions to strengthen the synergy between regional budgets,institutional budgets and payment by type of disease,and cautiously deal with the risks of excessive competition and"punching points"that may arise from the regional point method.

China's healthcare payment reform seeks to combine a medical insurance point-system with a global budget.The focus and difficulty in implementing the payment reform is how to make effectively link.On the basis of theoretical analysis,it selects the regions that have implemented the payment by disease under regional total budget and the payment by disease under institutional total budget,and summarizes the synergistic mechanism of total budget and payment by disease,including the strict control of total budget at the regional level,the reasonable setup of the budget or the standard of expected service volume at the institutional level,and the rate fluctuation and discount mechanism for the settlement of excess service;and further sort out the additional incentive mechanism to support innovation and quality enhancement under the background of the total budget and the payment by disease.Lessons can be drawn from the experiences of typical regions to strengthen the synergy between regional budgets,institutional budgets and payment by type of disease,and cautiously deal with the risks of excessive competition and"punching points"that may arise from the regional point method.

China's healthcare payment reform seeks to combine a medical insurance point-system with a global budget.The focus and difficulty in implementing the payment reform is how to make effectively link.On the basis of theoretical analysis,it selects the regions that have implemented the payment by disease under regional total budget and the payment by disease under institutional total budget,and summarizes the synergistic mechanism of total budget and payment by disease,including the strict control of total budget at the regional level,the reasonable setup of the budget or the standard of expected service volume at the institutional level,and the rate fluctuation and discount mechanism for the settlement of excess service;and further sort out the additional incentive mechanism to support innovation and quality enhancement under the background of the total budget and the payment by disease.Lessons can be drawn from the experiences of typical regions to strengthen the synergy between regional budgets,institutional budgets and payment by type of disease,and cautiously deal with the risks of excessive competition and"punching points"that may arise from the regional point method.

China's healthcare payment reform seeks to combine a medical insurance point-system with a global budget.The focus and difficulty in implementing the payment reform is how to make effectively link.On the basis of theoretical analysis,it selects the regions that have implemented the payment by disease under regional total budget and the payment by disease under institutional total budget,and summarizes the synergistic mechanism of total budget and payment by disease,including the strict control of total budget at the regional level,the reasonable setup of the budget or the standard of expected service volume at the institutional level,and the rate fluctuation and discount mechanism for the settlement of excess service;and further sort out the additional incentive mechanism to support innovation and quality enhancement under the background of the total budget and the payment by disease.Lessons can be drawn from the experiences of typical regions to strengthen the synergy between regional budgets,institutional budgets and payment by type of disease,and cautiously deal with the risks of excessive competition and"punching points"that may arise from the regional point method.

China's healthcare payment reform seeks to combine a medical insurance point-system with a global budget.The focus and difficulty in implementing the payment reform is how to make effectively link.On the basis of theoretical analysis,it selects the regions that have implemented the payment by disease under regional total budget and the payment by disease under institutional total budget,and summarizes the synergistic mechanism of total budget and payment by disease,including the strict control of total budget at the regional level,the reasonable setup of the budget or the standard of expected service volume at the institutional level,and the rate fluctuation and discount mechanism for the settlement of excess service;and further sort out the additional incentive mechanism to support innovation and quality enhancement under the background of the total budget and the payment by disease.Lessons can be drawn from the experiences of typical regions to strengthen the synergy between regional budgets,institutional budgets and payment by type of disease,and cautiously deal with the risks of excessive competition and"punching points"that may arise from the regional point method.