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 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.

Focal therapy for renal cell carcinoma is a precision treatment technique that directly targets and destroys cancerous lesions while preserving the maximum amount of surrounding healthy kidney tissue through localized intervention. It is primarily indicated for early-stage renal cell carcinoma in patients with tumors ≤4 cm in diameter (T 1a), particularly for those at higher surgical risk. Compared to traditional radical nephrectomy and partial nephrectomy, focal therapy offers several advantages, including lower physical demands on the patient, minimally invasive nature, reduced risk of complications, and faster recovery. The focal therapy techniques currently utilized in clinical practice include cryoablation, radiofrequency ablation, microwave ablation, irreversible electroporation, high-intensity focused ultrasound, and stereotactic body radiotherapy. This article reviews the principles of various focal therapy techniques, patient selection, and the oncological outcomes, complications, and renal function preservation associated with these focal therapies.

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.

Objective:To investigate the safety and prognosis of partial nephrectomy (PN) in the treatment of highly malignant non-clear renal cell carcinoma (nccRCC).Methods:Clinical data of 47 patients with cT 1N 0M 0 high malignant nccRCC treated in Changhai Hospital from March 2016 to March 2022 were retrospectively analyzed. All patients received PN. There were 34(72.3%) males and 13(27.7%) females. The mean age was (53.5±15.0) years, and average BMI, was(23.7±3.4)kg/m 2.The maximum tumor diameter was (29.8±12.6) mm, and R. E.N.A.L. score was 7(5-9), with 37(78.7%) cases of T 1a and 10(21.3%) cases of T 1b. The mean estimated glomerular filtration rate (eGFR) before surgery was (96.3±25.5) ml/ (min·1.73m 2). All patients underwent PN, including 1 patient (2.1%) undergoing open surgery, 29 patients (61.7%) undergoing laparoscopic surgery, and 17 patients (36.2%) undergoing robotic surgery. There were a total of 22(46.8%) cases of papillary cell carcinoma(pRCC)type Ⅱ, 4(8.5%) cases of collecting duct carcinoma (cdRCC), 9(19.1%) cases of MiT family translocated renal cell carcinoma (tRCC), 5(10.6%) cases of mucoid tubular and spindle cell carcinoma (mtSCC)and 7(14.9%) cases of unclassified renal cell carcinoma (uRCC). The surgical conversion rate, positive margin rate, operative time, intraoperative blood loss, complications, and postoperative hospital stay were analyzed. Preoperative and postoperative eGFR were analyzed, and overall survival (OS) and cancer specific survival (CSS) were calculated. Results:All the operations were successfully completed. No radical operation or open operation was performed, with operation time of(100±60) min and intraoperative blood loss of(100±59) ml. There were no intraoperative complication and 1 case (2.1%) suffered from postoperative complication. Postoperative hospital stay were 5 (4-6) days. The mean eGFR after surgery was (86.5±27.1) ml/(min·1.73m 2), and the difference was statistically significant ( P=0.041). In this study, the mean follow-up time was (45.7±20.9)months, and no adjuvant therapy was used after surgery. During the follow-up period, 2 patients died, who all of them were kidney cancer-related death, and both OS and CSS were 95.7% (45/47). Conclusions:PN is safe, feasible and has a good prognosis in the treatment of high malignant T 1 nccRCC. For tumors with clear imaging boundaries and complete envelope, complete tumor resection is more likely, postoperative follow-up should be strict, and no remedial radical or systemic treatment was required.

The gastroduodenal artery (GDA) has an important role in pancreatic surgery. Relevant literature was reviewed and sum-marized in this article, along with practical experiences from our center, in order to provide references for surgeons in dealing with anatomical variations of the GDA and postoperative bleeding. GDA has close relationships with the blood supply of surroun-ding organs and is the most common vessel associated with intra-abdominal bleeding after pancreatic surgery. Therefore, the GDA plays a crucial anatomical role that affects the strategies and approaches of pancreatic surgery . Preoperative assessment of GDA variations can be achieved through CT angio-graphy. During surgery, it is important to identify and dissect the GDA properly and protect its remnants. In cases of residual bleeding from the GDA, endovascular treatment or secondary laparo-tomy can be conducted.

Promoting medical preventive integration and improving its collaborative mechanism is an inevitable requirement for achieving the transformation of China′s medical and health care system from " disease centered" to " people′s health centered" and providing comprehensive and comprehensive health services for the people.This study established a research framework based on the SFIC model on the basis of clarifying the collaborative subjects of medical preventive integration, sorted out the dilemma of medical preventive integration collaborative governance in China from five aspects, including external environment, starting conditions, facilitative leadership, institutional design and collaborative process.In order to break the dilemma of medical preventive integration and promote collaborative governance among multiple subjects, the authors proposed such optimization strategies, including further improving relevant laws, regulations, and policy systems, filling resource gaps, attracting multiple entities to participate, providing reference for promoting China′s medical preventive integration work.

Objective:To investigate the epidemic characteristics of human brucellosis in Inner Mongolia Autonomous Region from 2018 to 2020, and provide a reliable scientific basis for formulating brucellosis prevention and control strategies in Inner Mongolia Autonomous Region.Methods:A retrospective study was carried out to collect data of human brucellosis in Inner Mongolia Autonomous Region from 2018 to 2020 from the "China Disease Control and Prevention Information System", and the monitoring data and information of confirmed cases were collected from the annual summary data reported by the leagues (cities) of the Inner Mongolia Autonomous Region. Using descriptive epidemiological methods, the epidemic situation, three distributions (time, region and population distributions) of brucellosis, and the serological and pathogenic test results of active monitoring population were analyzed.Results:From 2018 to 2020, a total of 40 665 cases of brucellosis were reported in Inner Mongolia Autonomous Region, with an annual average incidence rate of 53.47/100 000. The number of annual incidence had increased from 10 111 in 2018 to 16 406 in 2020, and the annual incidence rate had increased from 39.99/100 000 in 2018 to 64.60/100 000 in 2020. The spring and summer was the peak incidence, mainly in March to August, accounting for 64.90% (26 390/40 665) . There were reports of brucellosis cases in 12 leagues (cities) of Inner Mongolia Autonomous Region, and the top 3 regions with the number of reported cases were Tongliao City (9 896 cases), Xing'an League (6 136 cases) and Chifeng City (4 934 cases). The age of onset of brucellosis cases was mainly 30 - < 65 years old(33 539 cases), and the sex ratio between men and women was 2.18 ∶ 1.00 (27 890 ∶ 12 775); the occupational distribution was mainly farmers, accounting for 79.23% (32 221/40 665). From 2018 to 2020, 704 085 people were actively monitored in the region, of which 391 941 were serologically tested, and the infection rate was 4.57% (17 920/391 941); and there were 9 539 new cases in the active monitoring population. In 3 years, 19 strains of Brucella sheep type 3 and 11 strains of Brucella sheep type 1 were isolated. Conclusions:From 2018 to 2020, the incidence rate of brucellosis in Inner Mongolia Autonomous Region is increasing year by year. There are many new cases in the active monitoring population, and more underreporting cases. It is recommended to expand the scope of monitoring, strengthen pathogen monitoring among humans and animals, and joint prevention and control of various departments to improve the self-protection awareness of the masses.

Objective:To discuss the perioperative symptom change rule of patients with myasthenia gravis(MG), and to provide a theoretical basis for preventing and reducing the surgical risk of patients with MG.Methods:The clinical data of 104 patients who underwent thymectomy in the Department of Thoracic Surgery of the Second Affiliated Hospital of Zhengzhou University from 2015 to 2019 were retrospectively analyzed. According to the degree of the impact of MG symptoms on the body's physiology and life, the "MG dynamic classification standard" was formulated, which was divided into type 0-type Ⅳ according to the severity of MG symptoms. The symptoms of each patient of "admission", "preoperative" and "postoperative" are classified according to the "dynamic classification criteria", and the number of "admission", "preoperative" and "postoperative" were counted respectively. Based on the statistical analysis of each patient's type changes, the perioperative symptom changes of myasthenia gravis patients were summarized.Results:1. "Admission" classification: 12 cases of type 0, 42 cases of type Ⅰ, 32 cases of type Ⅱ, 12 cases of type Ⅲ, 5 cases of type Ⅳa, and 1 case of type Ⅳb. 2. "Preoperative" classification: 44 cases of type 0, 34 cases of type Ⅰ, 14 cases of type Ⅱ, 12 cases of type Ⅲ; 68 cases of preoperative symptom reduction (65.4%, 68/104), 36 cases of preoperative symptom stable (34.6%, 36/104). Asymptomatic aggravation. 3. "Postoperative" classification: 49 cases of type 0, 21 cases of type Ⅰ, 11 cases of type Ⅱ, 10 cases of type Ⅲ, 9 cases of type Ⅳa, 4 cases of type Ⅳb; 33 cases (31.7%, 33/104) had postoperative symptoms aggravated. Among the patients with worsening symptoms after surgery, 5 cases (15.2%, 5/33) worsened on the first day after surgery, 9 cases (27.2%, 9/33) worsened on the second day after surgery, and 13 cases (39.4%, 13/33) worsened on the third day after surgery. There were 4 cases (12.1%, 4/33) worsened on the 4th day, and 2 cases (6.1%, 2/33) worsened on the 5th day after surgery.Conclusion:MG patients had different conditions at admission. After individualized perioperative treatment, more than half of the patients' symptoms alleviated to varying degrees. After the operation, the symptoms of MG will be temporarily aggravated due to the effects of surgery and anesthesia, and the aggravation period is mostly on 1-3 days. Reasonable selection of low-risk MG patients for surgery, avoiding the superposition of other influencing factors in the postoperative exacerbation period, is expected to reduce the occurrence of postoperative crises in MG patients.

Spinal cord injury (SCI) is a disabling and destructive central nervous system injury that has not yet been successfully treated at this stage. Three-dimensional (3D) bioprinting has become a promising method to produce more biologically complex microstructures, which fabricate living neural constructs with anatomically accurate complex geometries and spatial distributions of neural stem cells, and this is critical in the treatment of SCI. With the development of 3D printing technology and the deepening of research, neural tissue engineering research using different printing methods, bio-inks, and cells to repair SCI has achieved certain results. Although satisfactory results have not yet been achieved, they have provided novel ideas for the clinical treatment of SCI. Considering the potential impact of 3D bioprinting technology on neural studies, this review focuses on 3D bioprinting methods widely used in SCI neural tissue engineering, and the latest technological applications of bioprinting of nerve tissues for the repair of SCI are discussed. In addition to introducing the recent progress, this work also describes the existing limitations and highlights emerging possibilities and future prospects in this field.