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 high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective:To compare the therapeutic effects of partial nephrectomy (PN) and cryoablation (CA) in patients with stage cT 1N 0M 0 renal cell carcinoma (RCC). Methods:A retrospective analysis was conducted on clinical data of patients with stage cT 1N 0M 0 RCC who underwent CA and PN treatment at The First Affiliated Hospital of Naval Medical University and Shanghai Ninth People's Hospital between March 2011 and December 2019. There were 50 cases in the CA group (36 from The First Affiliated Hospital of Naval Medical University and 14 from the Shanghai Ninth People's Hospital), and 1 323 cases in the PN group (all from The First Affiliated Hospital of Naval Medical University). PN included open surgery, laparoscopic surgery, or robotic surgery performed under general anesthesia through the abdominal or retroperitoneal approach. CA included laparoscopic surgery under general anesthesia and percutaneous treatment guided by CT or ultrasound under local anesthesia. Propensity score matching was performed based on baseline data of the patients to obtain balanced samples between the two groups using a 1∶2 nearest-neighbor matching method. After matching, comparisons were made between the two groups in terms of perioperative conditions, overall survival (OS), and recurrence-free survival (RFS). Results:After PSM, patient distributions were closely balanced in baseline data such as gender (male/female: 28/19 cases in CA group and 58/36 cases in PN group), age [66.0(53.0, 75.0) years vs. 59.5(50.0, 69.3) years], body mass index[ (24.1 ± 6.4) kg/m 2 vs. (24.1 ± 3.1) kg/m 2], Charlson comorbidity index [1(0, 2) vs. 1(0, 2)], history of malignant tumors [19.1% (9/47) vs. 17.0% (16/94)], preoperative estimated glomerular filtration rate (eGFR) [85.2(65.5, 97.1) ml/(min·1.73m 2) vs. 87.0(73.4, 100.4) ml/(min·1.73m 2)], and R. E.N.A.L. score [6(5, 7) vs. 7(6, 8)] between CA(n=47) and PN(n=94) group. There were significant differences in operative time [97.5(81.2, 117.5) min vs. 145.0(110.2, 185.0) min, P<0.001], estimated blood loss [85.0(50.0, 100.0) ml vs. 100.0(75.0, 200.0)ml, P=0.021], length of hospital stay [3.0(2.0, 4.0) days vs. 7.6(5.0, 9.0) days, P<0.001] between the CA and the PN group. No significant differences were observed in the incidence of postoperative complications [4.3% (2/47) vs. 5.3% (5/94), P=0.784], the eGFR within one week after surgery [83.7(65.6, 106.6) ml/(min·1.73m 2) vs. 83.2(66.7, 97.7) ml/(min·1.73m 2), P=0.645], the median follow-up time [ 93 (67, 126) months vs. 85 (68, 139) months, P=0.955], the RFS rate[81.8% vs. 96.8%, P=0.074], or the OS rate [85.7% vs. 97.8%, P=0.190] between the CA and the PN group. Conclusions:For patients with cT 1N 0M 0 stage RCC, CA and PN demonstrate comparable oncologic treatment efficacy, while CA offering the advantages of shorter surgical time, shorter hospital stay, and less blood loss.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.