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 explore the correlation between serum angiotensin-converting enzyme(SACE),matrix metalloproteinase-9(MMP-9)and haptoglobin(HPT)with pulmonary infection in patients with schizophrenia.Methods A total of 83 patients with schizophrenia were selected and divided into the infected group(40 cases)and the non-infected group(43 cases)according to whether they had pulmonary infection.Data of antipsychotic drugs,length of hospital stay,course of disease and electroconvulsive therapy were collected.Serum SACE,MMP-9 and HPT levels were detected by enzyme-linked immunosorbent assay.Spearman correlation analysis was used to determine serum SACE,MMP-9 and HPT and pulmonary infection in patients with schizophrenia.Logistic regression was used to analyze risk factors for pulmonary infection in patients with schizophrenia,and receiver operating characteristic(ROC)curves were used to evaluate the predictive value of serum SACE,MMP-9 and HPT in patients with pulmonary infection.Results Before treatment,the types of antipsychotic drugs≥2,the proportion of electroconvulsive therapy,serum SACE,MMP-9 and HPT levels were higher in the infected group than those in the non-infected group(P＜0.05).After treatment,there were no significant differences in serum SACE,MMP-9 and HPT levels between the infected group and the non-infected group(P＞0.05).Serum SACE,MMP-9 and HPT were positively correlated with pulmonary infection in patients with schizophrenia(P＜0.05).More than 2 types of antipsychotic drugs,electroconvulsive therapy and elevated SACE,MMP-9 and HPT were risk factors for pulmonary infection in schizophrenia patients(P＜0.05).The ROC curve analysis showed that the combined serum SACE,MMP-9 and HPT for pneumonia in schizophrenic patients were better than each of these indicators alone in predicting pulmonary infection in patients with schizophrenia.Conclusion Serum SACE,MMP-9 and HPT are related with pulmonary infection in patients with schizophrenia,and which can be used as potential indicators for predicting pulmonary infection in patients with schizophrenia.

Objective To explore the correlation between serum angiotensin-converting enzyme(SACE),matrix metalloproteinase-9(MMP-9)and haptoglobin(HPT)with pulmonary infection in patients with schizophrenia.Methods A total of 83 patients with schizophrenia were selected and divided into the infected group(40 cases)and the non-infected group(43 cases)according to whether they had pulmonary infection.Data of antipsychotic drugs,length of hospital stay,course of disease and electroconvulsive therapy were collected.Serum SACE,MMP-9 and HPT levels were detected by enzyme-linked immunosorbent assay.Spearman correlation analysis was used to determine serum SACE,MMP-9 and HPT and pulmonary infection in patients with schizophrenia.Logistic regression was used to analyze risk factors for pulmonary infection in patients with schizophrenia,and receiver operating characteristic(ROC)curves were used to evaluate the predictive value of serum SACE,MMP-9 and HPT in patients with pulmonary infection.Results Before treatment,the types of antipsychotic drugs≥2,the proportion of electroconvulsive therapy,serum SACE,MMP-9 and HPT levels were higher in the infected group than those in the non-infected group(P＜0.05).After treatment,there were no significant differences in serum SACE,MMP-9 and HPT levels between the infected group and the non-infected group(P＞0.05).Serum SACE,MMP-9 and HPT were positively correlated with pulmonary infection in patients with schizophrenia(P＜0.05).More than 2 types of antipsychotic drugs,electroconvulsive therapy and elevated SACE,MMP-9 and HPT were risk factors for pulmonary infection in schizophrenia patients(P＜0.05).The ROC curve analysis showed that the combined serum SACE,MMP-9 and HPT for pneumonia in schizophrenic patients were better than each of these indicators alone in predicting pulmonary infection in patients with schizophrenia.Conclusion Serum SACE,MMP-9 and HPT are related with pulmonary infection in patients with schizophrenia,and which can be used as potential indicators for predicting pulmonary infection in patients with schizophrenia.

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.