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 analyze the problems in implementing medical-research-industry collaborative innovation related policies, and propose corresponding countermeasures, for references for promoting the construction and development of collaborative innovation platforms in China.Methods:This study searched official websites such as the State Council, the National Health Commission and the Shanghai Municipal Health Commission for policy documents related to collaborative innovation and the transformation of medical scientific and technological achievements. Based on the Smith-model, 4 plaiforms of Shanghai were took, including the Clinical Science and Technology Innovation Park of Tongji University of Tenth People′s Hospital and other collaborative innovation platforms, as examples to analyze the problems in the implementation process of medical-research-industry collaborative innovation policies.Results:On the basis of national policies, Shanghai had issued a series of relevant guidance policies based on local conditions, creating a favorable policy environment for the construction and development of the medical-research-industry collaborative innovation platforms. However, the policy implications and practical needs related to collaborative innovation still needed to be continuously adjusted; The target demands of policy implementation entities were not unified, and there was a lack of normalized communication mechanisms; The target group lacked endogenous motivation and the policy implementation environment needed to be improved.Conclusions:The implementation of medical-research-industry collaborative innovation policies needed further improvement. It is suggested to optimize the policy supply coordination, performance evaluation and incentive mechanism, supervision and management, collaborative innovation culture atmosphere, and multi-channel funding support to promote the sustainable development of the collaborative innovation platform, and accelerate the efficient transformation of scientific and technological achievements.

Objective:To explore the value of three-dimensional automatic right ventricular quantitive analysis（3D Auto RVQ）technology in predicting the improvement of left ventricular ejection fraction（LVEF）in patients with heart failure with reduced ejection fraction（HFrEF）.Methods:A retrospective analysis was conducted on 89 HFrEF patients admitted to the Cardiology Department of Central China Fuwai Hospital of Zhengzhou University from April 2022 to June 2024. All patients received medication treatment and were further divided into heart failure with improved ejection fraction（HFimpEF）group and non HFimpEF group based on changes detected by echocardiography in LVEF after treatment. The clinical data，biological indicators，and medication treatment status of patients were collected，routine echocardiographic parameters and right ventricular strain parameters were measured，3D right ventricular ejection fraction（3D-RVEF），3D right ventricular stroke volume index（3D-RVSVI），3D right ventricular end-diastolic volume index（3D-RVEDVI），3D right ventricular end-systolic volume index（3D-RVESVI），3D tricuspid annular plane systolic excursion（3D-TAPSE），and 3D right ventricular fractional area change（3D-RVFAC）were measured using 3D Auto RVQ technology. The differences of the above parameters between the two groups were compared. The ROC curve was used to analyze the predictive efficiency of right ventricular parameters for HFimpEF，and the area under ROC curve（AUC）was calculated and compared. Logistic regression models were used to analyze the predictive value of right ventricular parameters for HFimpEF.Results:Compared with the non HFimpEF group，the HFimpEF group had a younger age，shorter heart failure course，a smaller proportion of males，New York Heart Association（NYHA）functional class ≥Ⅲ，and patients with concomitant coronary heart disease. The baseline LVEF，absolute value of two dimensional right ventricular global longitudinal strain（2D-RVGLS），3D-RVEF，3D-TAPSE，and 3D-RVSVI were higher in the HFimpEF group（all P<0.05）. ROC curve analysis showed that the AUC of 3D-RVEF for predicting HFimpEF was 0.858，and the predictive efficiency was higher than other right ventricular parameters. According to the Yoden index，the optimal cutoff value for predicting HFimpEF based on 3D-RVEF was 36.2%，with a corresponding sensitivity of 84.0% and specificity of 75.0%. After adjusting for clinical and other echocardiographic parameters，the logistic regression model showed that 3D-RVEF was an independent predictor of HFimpEF（ OR=1.435，95% CI=1.145-1.800， P<0.05）. Conclusions:The 3D-RVEF evaluated by 3D Auto RVQ technology has high predictive value for HFimpEF，which can provide a reference for clinical treatment，thereby improving the prognosis of HFrEF patients.

Objective To investigate the metabolic characteristics of patients with early-onset type 2 diabetes mellitus(T2DM)and to develop a risk prediction model for microvascular complications.Methods A retrospective study was conducted on 980 T2DM patients admitted for treatment between April 2020 and April 2024.Based on age at diagnosis,the patients were divided into two groups,an early-onset T2DM group(age at diagnosis<40 years,n=265)and a late-onset T2DM group(age at diagnosis≥40 years,n=715).Differences in metabolic indicators between the two groups were compared.Patients in the early-onset group were further divided into a complication subgroup(n=142)and a non-complication subgroup(n=123)based on the presence or absence of microvascular complications.Data on baseline characteristics,metabolic parameters,and laboratory indicators were collected and compared between the two groups.Multivariate logistic regression analysis was used to identify independent risk factors for microvascular complications,and a nomogram prediction model was constructed.The model's discriminative performance was assessed using receiver operating characteristic(ROC)curves,and its calibration was evaluated using calibration curves and the Hosmer-Lemeshow test.Decision curve analysis(DCA)was also performed to assess the model's clinical utility.Results Compared with the late-onset group,patients in the early-onset group exhibited more pronounced metabolic abnormalities,including higher body mass index(BMI),proportion of family history of diabetes mellitus,glycated hemoglobin(HbA1c)levels,total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),triglyceride-glucose index(TyG),and lactate dehydrogenase(LDH)levels(all P<0.05),along with a shorter disease duration and lower levels of high-density lipoprotein cholesterol(HDL-C)(P<0.05).According to a multivariate analysis,systolic blood pressure(SBP),total bilirubin(TBIL),HDL-C,LDL-C,TyG,and LDH were identified as independent risk factors for microvascular complications in patients with early-onset T2DM.A predictive model based on these factors was established as the follows,Log(P)=-19.915+0.017×SBP-0.136×TBIL-1.241×HDL-C+0.684×LDL-C+0.769×TyG+0.050×LDH.The area under the ROC curve(AUC)was 0.864(95%CI,0.820-0.907),and the Hosmer-Lemeshow test indicated good model fit(χ2=10.286,P=0.246).The slope of the DCA curve was also close to 1.Conclusion The nomogram prediction model based on SBP,TBIL,HDL-C,LDL-C,TyG,and LDH demonstrates good predictive performance for microvascular complications and can provide a reference for clinical risk stratification and individualized intervention.

Objective:To investigate the surgical effect of total parathyroidectomy combined with calf subcutaneous autotransplantation in the treatment of secondary hyperparathyroidism.Method:From Dec 2018 to Dec 2022,31 patients with secondary hyperparathyroidism who underwent total parathyroidectomy combined with calf subcutaneous autotransplantation in our hospital were selected to analyze the therapeutic effect.Results:All 31 operations were successfully completed.A total of 120 parathyroid glands were removed,including 27 cases(87.10%)with 4 parathyroid glands and 4 cases(12.90%)with 3 parathyroid glands.The average length of hospitalization was(15.82±8.74)days.Compared with preoperative parathyroid hormone,the value of parathyroid hormone decreased by more than 50%after 20 min of total parathyroidectomy.The levels of serum calcium,phosphorus,iPTH and calcium-phosphorus product at each time point after operation were significantly lower than those before operation(P＜0.01).The symptoms of joint pain was significantly improved in all patients after operation.During the postoperative follow-up of 31 patients,1 patient was confirmed to have graft recurrence at 6 months after operation,which was surgically removed.Conclusion:Total parathyroidectomy combined with calf subcutaneous autotransplantation can effectively treat secondary hyperparathyroidism and significantly improve the quality of life.

Objective To compare the factors associated with gestational diabetes mellitus(GDM)between ethnic minorities pregnant women and Han pregnant women in Guizhou.Methods A retrospective analysis was performed in individuals who gave birth in representative hospitals in various regions of Guizhou province from January 2021 to June 2021.A strict screening was carried out according to the inclusion and exclusion criteria,and clinical data were collected from 2673 individuals,including 856 ethnic minorities pregnant women and 1817 Han pregnant women.All the inidviduals were divided into GDM group and non-GDM group according to the results of OGTT at 24～28 weeks of gestation.The results of general information,blood routine,and biochemical examination were compared between the two groups.Results In ethnic minorities in Guizhou region,age,gestational weight gain(GWG)≥11.5 kg,unemployed,pregnancy times≥2,parity times≥2 and irregular prenatal examination during pregnancy were higher,and platelet count was higher,while the total protein(TP)and albumin(ALB)were lower in GDM group than in non-GDM group(P<0.05).Logistic regression analysis showed that unemployed,pregnancy times≥2,parity times≥2,irregular prenatal examination during pregnancy,TP and ALB levels were influencing factors for GDM in ethnic minorities in Guizhou region(P<0.05).In Han pregnant women in Guizhou region,the age,proportion of GWG≥11.5 kg,unemployed,pregnancy times≥2,parity times≥2,irregular prenatal examination during pregnancy,direct bilirubin(D-BIL)and urea nitrogen(BUN)were higher,and in GDM group than in non-GDM group(P<0.05).Logistic regression analysis showed that GWG≥11.5 kg,pregnancy times≥2,parity times=1,parity times≥2,irregular prenatal examination during pregnancy,D-BIL and BUN were influencing factors for GDM in Han pregnant women in Guizhou region(P<0.05).Conclusions The same influencing factors for the occurrence of GDM between ethnic minorities and Han nationality in Guizhou were no occupation,pregnancy and parity times≥2,and irregular prenatal examination during pregnancy.TP and ALB levels were the influencing factors for GDM among ethnic minorities.D-BIL and BUN are the influencing factors for GDM in Han nationality.Ethnic minorities and Han pregnant women in Guizhou region should take personalized prevention and intervention measures to guide GDM monitoring and early intervention.

Objective:To investigate the surgical effect of total parathyroidectomy combined with calf subcutaneous autotransplantation in the treatment of secondary hyperparathyroidism.Method:From Dec 2018 to Dec 2022,31 patients with secondary hyperparathyroidism who underwent total parathyroidectomy combined with calf subcutaneous autotransplantation in our hospital were selected to analyze the therapeutic effect.Results:All 31 operations were successfully completed.A total of 120 parathyroid glands were removed,including 27 cases(87.10%)with 4 parathyroid glands and 4 cases(12.90%)with 3 parathyroid glands.The average length of hospitalization was(15.82±8.74)days.Compared with preoperative parathyroid hormone,the value of parathyroid hormone decreased by more than 50%after 20 min of total parathyroidectomy.The levels of serum calcium,phosphorus,iPTH and calcium-phosphorus product at each time point after operation were significantly lower than those before operation(P＜0.01).The symptoms of joint pain was significantly improved in all patients after operation.During the postoperative follow-up of 31 patients,1 patient was confirmed to have graft recurrence at 6 months after operation,which was surgically removed.Conclusion:Total parathyroidectomy combined with calf subcutaneous autotransplantation can effectively treat secondary hyperparathyroidism and significantly improve the quality of life.

Objective To compare the factors associated with gestational diabetes mellitus(GDM)between ethnic minorities pregnant women and Han pregnant women in Guizhou.Methods A retrospective analysis was performed in individuals who gave birth in representative hospitals in various regions of Guizhou province from January 2021 to June 2021.A strict screening was carried out according to the inclusion and exclusion criteria,and clinical data were collected from 2673 individuals,including 856 ethnic minorities pregnant women and 1817 Han pregnant women.All the inidviduals were divided into GDM group and non-GDM group according to the results of OGTT at 24～28 weeks of gestation.The results of general information,blood routine,and biochemical examination were compared between the two groups.Results In ethnic minorities in Guizhou region,age,gestational weight gain(GWG)≥11.5 kg,unemployed,pregnancy times≥2,parity times≥2 and irregular prenatal examination during pregnancy were higher,and platelet count was higher,while the total protein(TP)and albumin(ALB)were lower in GDM group than in non-GDM group(P<0.05).Logistic regression analysis showed that unemployed,pregnancy times≥2,parity times≥2,irregular prenatal examination during pregnancy,TP and ALB levels were influencing factors for GDM in ethnic minorities in Guizhou region(P<0.05).In Han pregnant women in Guizhou region,the age,proportion of GWG≥11.5 kg,unemployed,pregnancy times≥2,parity times≥2,irregular prenatal examination during pregnancy,direct bilirubin(D-BIL)and urea nitrogen(BUN)were higher,and in GDM group than in non-GDM group(P<0.05).Logistic regression analysis showed that GWG≥11.5 kg,pregnancy times≥2,parity times=1,parity times≥2,irregular prenatal examination during pregnancy,D-BIL and BUN were influencing factors for GDM in Han pregnant women in Guizhou region(P<0.05).Conclusions The same influencing factors for the occurrence of GDM between ethnic minorities and Han nationality in Guizhou were no occupation,pregnancy and parity times≥2,and irregular prenatal examination during pregnancy.TP and ALB levels were the influencing factors for GDM among ethnic minorities.D-BIL and BUN are the influencing factors for GDM in Han nationality.Ethnic minorities and Han pregnant women in Guizhou region should take personalized prevention and intervention measures to guide GDM monitoring and early intervention.

Objective:To analyze the problems in implementing medical-research-industry collaborative innovation related policies, and propose corresponding countermeasures, for references for promoting the construction and development of collaborative innovation platforms in China.Methods:This study searched official websites such as the State Council, the National Health Commission and the Shanghai Municipal Health Commission for policy documents related to collaborative innovation and the transformation of medical scientific and technological achievements. Based on the Smith-model, 4 plaiforms of Shanghai were took, including the Clinical Science and Technology Innovation Park of Tongji University of Tenth People′s Hospital and other collaborative innovation platforms, as examples to analyze the problems in the implementation process of medical-research-industry collaborative innovation policies.Results:On the basis of national policies, Shanghai had issued a series of relevant guidance policies based on local conditions, creating a favorable policy environment for the construction and development of the medical-research-industry collaborative innovation platforms. However, the policy implications and practical needs related to collaborative innovation still needed to be continuously adjusted; The target demands of policy implementation entities were not unified, and there was a lack of normalized communication mechanisms; The target group lacked endogenous motivation and the policy implementation environment needed to be improved.Conclusions:The implementation of medical-research-industry collaborative innovation policies needed further improvement. It is suggested to optimize the policy supply coordination, performance evaluation and incentive mechanism, supervision and management, collaborative innovation culture atmosphere, and multi-channel funding support to promote the sustainable development of the collaborative innovation platform, and accelerate the efficient transformation of scientific and technological achievements.

Objective:To explore the value of three-dimensional automatic right ventricular quantitive analysis（3D Auto RVQ）technology in predicting the improvement of left ventricular ejection fraction（LVEF）in patients with heart failure with reduced ejection fraction（HFrEF）.Methods:A retrospective analysis was conducted on 89 HFrEF patients admitted to the Cardiology Department of Central China Fuwai Hospital of Zhengzhou University from April 2022 to June 2024. All patients received medication treatment and were further divided into heart failure with improved ejection fraction（HFimpEF）group and non HFimpEF group based on changes detected by echocardiography in LVEF after treatment. The clinical data，biological indicators，and medication treatment status of patients were collected，routine echocardiographic parameters and right ventricular strain parameters were measured，3D right ventricular ejection fraction（3D-RVEF），3D right ventricular stroke volume index（3D-RVSVI），3D right ventricular end-diastolic volume index（3D-RVEDVI），3D right ventricular end-systolic volume index（3D-RVESVI），3D tricuspid annular plane systolic excursion（3D-TAPSE），and 3D right ventricular fractional area change（3D-RVFAC）were measured using 3D Auto RVQ technology. The differences of the above parameters between the two groups were compared. The ROC curve was used to analyze the predictive efficiency of right ventricular parameters for HFimpEF，and the area under ROC curve（AUC）was calculated and compared. Logistic regression models were used to analyze the predictive value of right ventricular parameters for HFimpEF.Results:Compared with the non HFimpEF group，the HFimpEF group had a younger age，shorter heart failure course，a smaller proportion of males，New York Heart Association（NYHA）functional class ≥Ⅲ，and patients with concomitant coronary heart disease. The baseline LVEF，absolute value of two dimensional right ventricular global longitudinal strain（2D-RVGLS），3D-RVEF，3D-TAPSE，and 3D-RVSVI were higher in the HFimpEF group（all P<0.05）. ROC curve analysis showed that the AUC of 3D-RVEF for predicting HFimpEF was 0.858，and the predictive efficiency was higher than other right ventricular parameters. According to the Yoden index，the optimal cutoff value for predicting HFimpEF based on 3D-RVEF was 36.2%，with a corresponding sensitivity of 84.0% and specificity of 75.0%. After adjusting for clinical and other echocardiographic parameters，the logistic regression model showed that 3D-RVEF was an independent predictor of HFimpEF（ OR=1.435，95% CI=1.145-1.800， P<0.05）. Conclusions:The 3D-RVEF evaluated by 3D Auto RVQ technology has high predictive value for HFimpEF，which can provide a reference for clinical treatment，thereby improving the prognosis of HFrEF patients.