OBJECTIVE: To investigate the mechanism of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSC) in alleviating brain injury after resuscitation in swine with cardiac arrest (CA). METHODS: Twenty-nine healthy male large white swine were randomly divided into Sham group (n = 9), cardiopulmonary resuscitation (CPR) group (n = 10) and hESC-MSC group (n = 10). The Sham group only completed animal preparation. In CPR group and hESC-MSC group, the swine model of CA-CPR was established by inducing ventricular fibrillation for 10 minutes with electrical stimulation and CPR for 6 minutes. At 5 minutes after successful resuscitation, hESC-MSC 2.5×10⁶/kg was injected via intravenous micropump within 1 hour in hESC-MSC group. Venous blood samples were collected before resuscitation and at 4, 8, 24, 48 and 72 hours of resuscitation. The levels of neuron specific enolase (NSE) and S100B protein (S100B) were detected by enzyme linked immunosorbent assay (ELISA). At 24, 48 and 72 hours of resuscitation, neurological deficit score (NDS) and cerebral performance category (CPC) were used to evaluate the neurological function of the animals. Three animals from each group were randomly selected and euthanized at 24, 48, and 72 hours of resuscitation, and the hippocampus tissues were quickly obtained. Immunofluorescence staining was used to detect the distribution of hESC-MSC in hippocampus. Immunohistochemical staining was used to detect the activation of astrocytes and microglia and the survival of neurons in the hippocampus. The degree of apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). RESULTS: The serum NSE and S100B levels of brain injury markers in CPR group and hESC-MSC group were significantly higher than those in Sham group at 24 hours of resuscitation, and then gradually increased. The levels of NSE and S100B in serum at each time of resuscitation in hESC-MSC group were significantly lower than those in CPR group [NSE (μg/L): 20.69±3.62 vs. 28.95±3.48 at 4 hours, 27.04±5.56 vs. 48.59±9.22 at 72 hours; S100B (μg/L): 2.29±0.39 vs. 3.60±0.73 at 4 hours, 2.38±0.15 vs. 3.92±0.50 at 72 hours, all P < 0.05]. In terms of neurological function, compared with the Sham group, the NDS score and CPC score in the CPR group and hESC-MSC group increased significantly at 24 hours of resuscitation, and then gradually decreased. The NDS and CPC scores of hESC-MSC group were significantly lower than those of CPR group at 24 hours of resuscitation (NDS: 111.67±20.21 vs. 170.00±21.79, CPC: 2.33±0.29 vs. 3.00±0.00, both P < 0.05). The expression of hESC-MSC positive markers CD73, CD90 and CD105 in the hippocampus of hESC-MSC group at 24, 48 and 72 hours of resuscitation was observed under fluorescence microscope, indicating that hESC-MSC could homing to the damaged hippocampus. In addition, compared with Sham group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of CPR group were significantly increased, and the proportion of neurons was significantly decreased at 24, 48 and 72 hours of resuscitation. Compared with CPR group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of hESC-MSC group decreased and the proportion of neurons increased significantly at 24 hours of resuscitation [proportion of astrocytes: (14.33±1.00)% vs. (30.78±2.69)%, proportion of microglia: (12.00±0.88)% vs. (27.89±5.68)%, apoptotic index: (12.89±3.86)% vs. (52.33±7.77)%, proportion of neurons: (39.44±3.72)% vs. (28.33±1.53)%, all P < 0.05]. CONCLUSIONS Application of hESC-MSC at the early stage of resuscitation can reduce the brain injury and neurological dysfunction after resuscitation in swine with CA. The mechanism may be related to the inhibition of immune cell activation, reduction of cell apoptosis and promotion of neuronal survival.
Animals ; Heart Arrest/therapy* ; Cardiopulmonary Resuscitation ; Swine ; Humans ; Male ; Human Embryonic Stem Cells/cytology* ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology* ; Phosphopyruvate Hydratase/blood* ; Brain Injuries/therapy* ; S100 Calcium Binding Protein beta Subunit ; Apoptosis ; Disease Models, Animal

Objective:To explore the clinical effect of the whole-process management scheme of daytime minimally invasive liver resection surgery based on the enhanced recovery after surgery (ERAS) concept.Methods:This is a retrospective case series study. The data of 55 patients who underwent minimally invasive daytime liver resection surgery under the ERAS concept at the Department of General Surgery,Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2023 to August 2024. There were 22 males and 33 females;aged (48.2±15.1) years (range: 16 to 77 years). All patients were classified as Grade 2 according to the American Society of Anesthesiologists physical status classification. Among them, 7 cases were complicated with liver cirrhosis and 10 cases had fatty liver. A multidisciplinary team was formed, consisting of surgeons, anesthesiologists, rehabilitation physicians, psychologists, pharmacists, acute pain management team, operating room nurses, day surgery ward nurses, and ERAS specialized nurses. After strict evaluation by surgeons and anesthesiologists, patients suitable for daytime liver resection surgery were implemented with the ERAS whole-process management plan for liver resection on the basis of routine nursing care.Results:Among the 55 patients, 50 were discharged smoothly within 48 hours, while 5 were transferred to specialized departments for further treatment due to not meeting the discharge criteria, with a smooth daytime discharge rate of 90.9%. Among the 50 patients, 30 underwent laparoscopic surgery and 20 underwent robotic-assisted surgery. The surgery time was (91.6±28.2)minutes(range:45 to 165 minutes), with the intraoperative blood loss of only (30.5±25.5)ml(range:5 to 100 ml). Pathological examination results showed that among the 50 patients, 13 cases had hepatocellular carcinoma, 21 cases had hepatic hemangioma, 4 cases had hepatic cyst, 8 cases had focal nodular hyperplasia, 1 case had low-grade dysplastic nodule, 1 case had hepatolithiasis, 1 case had lymphoma, and 1 case had vascular, fibrous and lymphoid tissue proliferation. There were 44.0% patients who were able to get out of bed on the day of surgery. The hospital stay was (1.8±0.4)days(range:1 to 2 days), and the hospitalization cost was (34 499±20 330)yuan(range:11 724 to 73 488 yuan). No complications requiring special treatment outside the conventional pathway were observed during the hospital stay and follow-up period. At the 2-week outpatient follow-up, no significant abnormalities were found in all patients, and the wound healing was good.Conclusions:The daytime liver resection surgery based on the ERAS whole-process management plan has shown good feasibility in clinical practice. It helps to simplify medical process, shorten hospital stay, and reduce medical costs.

Objective:To explore the clinical effect of the whole-process management scheme of daytime minimally invasive liver resection surgery based on the enhanced recovery after surgery (ERAS) concept.Methods:This is a retrospective case series study. The data of 55 patients who underwent minimally invasive daytime liver resection surgery under the ERAS concept at the Department of General Surgery,Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2023 to August 2024. There were 22 males and 33 females;aged (48.2±15.1) years (range: 16 to 77 years). All patients were classified as Grade 2 according to the American Society of Anesthesiologists physical status classification. Among them, 7 cases were complicated with liver cirrhosis and 10 cases had fatty liver. A multidisciplinary team was formed, consisting of surgeons, anesthesiologists, rehabilitation physicians, psychologists, pharmacists, acute pain management team, operating room nurses, day surgery ward nurses, and ERAS specialized nurses. After strict evaluation by surgeons and anesthesiologists, patients suitable for daytime liver resection surgery were implemented with the ERAS whole-process management plan for liver resection on the basis of routine nursing care.Results:Among the 55 patients, 50 were discharged smoothly within 48 hours, while 5 were transferred to specialized departments for further treatment due to not meeting the discharge criteria, with a smooth daytime discharge rate of 90.9%. Among the 50 patients, 30 underwent laparoscopic surgery and 20 underwent robotic-assisted surgery. The surgery time was (91.6±28.2)minutes(range:45 to 165 minutes), with the intraoperative blood loss of only (30.5±25.5)ml(range:5 to 100 ml). Pathological examination results showed that among the 50 patients, 13 cases had hepatocellular carcinoma, 21 cases had hepatic hemangioma, 4 cases had hepatic cyst, 8 cases had focal nodular hyperplasia, 1 case had low-grade dysplastic nodule, 1 case had hepatolithiasis, 1 case had lymphoma, and 1 case had vascular, fibrous and lymphoid tissue proliferation. There were 44.0% patients who were able to get out of bed on the day of surgery. The hospital stay was (1.8±0.4)days(range:1 to 2 days), and the hospitalization cost was (34 499±20 330)yuan(range:11 724 to 73 488 yuan). No complications requiring special treatment outside the conventional pathway were observed during the hospital stay and follow-up period. At the 2-week outpatient follow-up, no significant abnormalities were found in all patients, and the wound healing was good.Conclusions:The daytime liver resection surgery based on the ERAS whole-process management plan has shown good feasibility in clinical practice. It helps to simplify medical process, shorten hospital stay, and reduce medical costs.

The clinical data of one child with metanephric stromal tumor (MST) and BRAF V600E gene mutation admitted to the First Affiliated Hospital of Zhengzhou University in June 2022 was analyzed retrospectively.Literature was reviewed.The patient, a 2-year-old girl, was diagnosed with a tumor in the left abdomen.The maximum diameter of the tumor was 10.5 cm.A radical nephrectomy was performed on the left kidney, and postoperative pathology revealed MST.Microscopically, the tumor had no envelope and exhibited expansive growth.The tumor cells were fusiform or stellate, and nuclear division was visible in the cell-rich region.Dysplastic blood vessels were seen inside the tumor.The tumor cells around the blood vessels and invaginated renal tubules were arranged like onion skin.CD34 was detected positive by immunohistochemical staining, and BRAF V600E mutation was also detected positive by fluorescent polymerase chain reaction.A total of 21 relevant case reports were retrieved, including 16 in English and 5 in Chinese.Fifty-eight MST patients, including the one in this report were analyzed.These patients were aged 2 days to 15 years, with a median age of 2 years.Except for 2 patients with unknown sex, the ratio of male to female was about 1.4∶1.0.Most MST patients were asymptomatic, with an average tumor size of 5.3 cm.The tumor cell CD34 showed positive expression in different degrees.Eight patients received the BRAF V600E mutation detection, and the results were all positive.Fifty-eight patients underwent nephrectomy and were followed up for 0-156 months, of which 7 patients were assisted with radiotherapy and chemotherapy.During the follow-up, 1 patient died, and 1 patient had a relapse.MST is a rare benign renal stromal tumor. BRAF V600E mutations are detected in a variety of malignancies.This paper is the first to report MST with BRAF V600E mutation in China and points out the importance of molecular detection of BRAF mutation for accurate diagnosis of MST.

FLASH radiotherapy (FLASH-RT) has garnered considerable attention globally in recent years. Compared to conventional radiotherapy, FLASH-RT can deliver the total radiation dose to the target volume in an extremely short time, reducing the radiation-induced damage to normal tissue while maintaining similar anti-tumor effects. FLASH-RT has been in the clinical trial stage, with several clinical research result being reported. Based on the collected global clinical research result of FLASH-RT in recent years, this study systematically reviewed FLASH-RT′s safety, radiation-related side effects, treatment efficacy, opportunities, and challenges in clinical trials.

Objective:To explore the protective efficacy of sulforaphane (SFN) in alleviating intestinal mucosal injury after resuscitation in pigs and its possible mechanism.Methods:This experiment was performed in the laboratory animal center, Zhejiang university. Using a random number table, twenty-four domestic healthy male white pigs were randomly divided into the Sham group, cardiopulmonary resuscitation (CPR) group, and SFN group, in which the Sham group had 6 pigs, and the other two groups had 9 pigs, respectively. The experimental parameters of 10 min of cardiac arrest and 6 min of CPR were chosen to establish the porcine model of CPR in the CPR and SFN groups. At 5 min after resuscitation, a dose of 2 mg/kg of SFN was infused via the femoral vein within 10 min in the SFN group. At 1 h, 2 h, 4 h, and 24 h after resuscitation, vein samples were collected, and then the levels of intestinal fatty acid binding protein (IFABP) and diamine oxidase (DAO) in serum were measured by ELISA. Subsequently, 6 pigs were chosen to be euthanized in each group, and then tissue samples were harvested from distal ileum to measure the level of cell apoptosis by TUNEL, the activities of superoxide dismutase (SOD) and catalase (CAT) and the contents of glutathione (GSH) and malondialdehyde (MDA) by biochemical method, the contents of 4-hydroxy-2-nonenal (4-HNE) by ELISA, the fluorescence intensity of reactive oxygen species (ROS) by immunofluorescence staining, and the expression levels of zonula occluden-1 (ZO-1), occludin, nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) by Western blot. Continuous variables were compared with one way analysis of variance among the three groups, and Bonferroni test was used for further pairwise comparison.Results:During the observation period after resuscitation, the serum levels of biomarkers of intestinal mucosal injury including IFABP and DAO were significantly higher in the CPR and SFN groups than in the Sham group (all P<0.05). However, the serum levels of IFABP at 2 h, 4 h, and 24 h after resuscitation and the serum levels of DAO at 1 h, 2 h, 4 h, and 24 h after resuscitation were significantly lower in the SFN group than in the CPR group (all P<0.05). At 24 h after resuscitation, apoptotic index was significantly increased, SOD and CAT activities and GSH contents were significantly decreased, MDA and 4-HNE contents and ROS production were significantly increased, ZO-1 and occludin expression were significantly down-regulated, and Nrf2 and HO-1 expression were significantly up-regulated in the CPR and SFN groups when compared with the Sham group (all P<0.05). However, apoptotic index was significantly decreased, SOD and CAT activities and GSH contents were significantly increased, MDA and 4-HNE contents and ROS production were significantly decreased, and ZO-1, occludin, Nrf2, and HO-1 expression were significantly up-regulated in the SFN group when compared to the CPR group (all P<0.05). Conclusion:SFN could effectively protect against intestinal mucosal injury after resuscitation in pigs, and its mechanism was possibly related to the inhibition of oxidative stress and cell apoptosis via the activation of Nrf2/HO-1 pathway.

Objective:To establish pig cardiac arrest resuscitation model, and explore the effect of automatic compression synchronous ventilation (ACSV) on cardiopulmonary resuscitation in pigs.Methods:Twelve male white pigs with body weight of (38±3) kg were divided into ACSV group and intermittent positive pressure ventilation (IPPV) group with 6 pigs in each group by random number table method. A porcine cardiac arrest and resuscitation model was prepared with ventricular fibrillation induced by alternating current release via right ventricular electrode for 6 min and compression for 8 min. Mechanical chest external compression depth 5 cm, frequency 100 times/min. The tidal volume of ACSV group was 3 mL/kg and the frequency was 100 times/min. In the IPPV group, the tidal volume was 7 mL/kg and the frequency was 10 times/min. Arterial blood was drawn before resuscitation and at 1, 4 and 7min during resuscitation for blood gas analysis. Coronary perfusion pressure (CPP), end-respiratory carbon dioxide (ETCO 2) and carotid blood flow (CBF) were monitored during resuscitation. Stroke volume (SV) and global ejection fraction (GEF) were recorded by pressure monitoring catheter before and 1, 2 and 4 h after resuscitation. Venous blood samples were collected at each time point and 24 h after resuscitation to detect cardiac troponin I (cTnI), neuron specific enolase (NSE), alamine aminotransferase (ALT), creatinine (Cr), and intestinal fatty acid binding protein (IFABP). Results:(1) During resuscitation, CPP, ETCO 2 and CBF in ACSV group were slightly higher than those in IPPV group, but the differences between groups were not statistically significant. (2) There was no significant difference in pH, PaCO 2, HCO 3- and lactic acid between the two groups during resuscitation. The PaO 2 in ACSV group was higher than that in IPPV group, and the difference was statistically significant at 4 and 7 min. (3) The success rate of resuscitation in both groups was 83.3%, and there was no significant difference in SV and GEF before and after resuscitation. (4) After resuscitation, cTnI, NSE, ALT, Cr, iFABP and other indexes in ACSV group were lower than those in IPPV group, and there were statistically significant differences in cTnI at 24 h after resuscitation, ALT at 2 h and 24 h after resuscitation, and IFABP at 4 h and 24 h after resuscitation (all P<0.05). Conclusions:This study preliminarily suggested that the novel ACSV could significantly improve the oxygen supply level during cardiopulmonary resuscitation in pigs, while keeping the compression efficiency unchanged, avoiding hyperventilation, and reducing multiple organ damage after resuscitation, which is worthy of further study.

ObjectiveTo analyze the epidemiological characteristics and related factors of pesticide poisoning occurred in daily life in Tiantai County, Zhejiang Province from 2015 to 2023, and to provide a basis for the prevention and control of pesticide poisoning. MethodsThe information of pesticide poisoning cases was obtained from the occupational disease and occupational health information monitoring system of the China Disease Prevention and Control Information System, death data was obtained from the Zhejiang Province Chronic Disease Surveillance Information Management System, so that the poisoning incidence rate and the fatality rate were analyzed. ResultsA total of 439 cases of pesticide poisoning occurred in life were reported in Tiantai County from 2015 to 2023, of which mainly concentrated in the second quarter of each year, with an average annual incidence rate of 10.62/10⁵ and fatality rate of 14.81%.The main cause of poisoning in < 15 years old group was accidental ingestion, while the main cause in ≥15 years old group was self-poisoning, and the difference was statistically significant (χ²＝103.518, P<0.001).The average annual incidence of pesticide poisoning occurred in life in the urban area was significantly lower than that in the rural area, and the difference was statistically significant (χ²＝30.871, P<0.001).The main types of pesticide poisoning were insecticides (65.15%), and paraquat had the highest fatality rate (47.73%). The results of binary logistic regression analysis indicated that age and types of pesticide poisoning may be the independent risk factors affecting the fatality of pesticide poisoning in daily life. ConclusionPesticide poisoning occurred frequently in Tiantai County over the years, and mainly occurred in summer, rural areas. Except for <15 years old group who were accidental ingestion,the other cases were mainly self-poisoning. The elderly and herbicide users should be the focus of key intervention targets. It is suggested to take personalized preventive and curative measures to intervene by age, seasons, regions and types to reduce the incidence and fatality rate of pesticide poisoning in daily life, and strengthen psychological health interventions to the cases of attempting to suicide.

Objective:To evaluate the safety and efficacy of a novel domestic extracorporeal membrane oxygenation (ECMO) mainframe in a porcine model, and to provide the basis for further clinical application.Methods:Five domestic healthy male white pigs, weighing (51±4) kg, were selected. The ECMO system was established by using a novel ECMO mainframe with imported membrane oxygenator and pipeline, and continued to run for 72 hours. ECMO parameters are as follows: veno-arterial ECMO, centrifugal pump speed 3 000-3 500 r/min, continuous infusion of heparin anticoagulation to maintain the activate clotting time (ACT) of 140-200 s. Real-time monitoring of speed, flow, pressure before pump, pressure after pump, pressure after membrane and other equipment parameters, and the equipment performance was scored. The changes of hemodynamics, blood lactic acid and blood routine were monitored dynamically. Repeated measures analysis of variance was used to compare different time points within the group. At the end of the experiment, the thrombosis in the pump head and oxygenator was observed. The animals were sacrificed to obtain the tissue samples of the main organs for gross observation and pathological injury evaluation.Results:All animals successfully ran the ECMO system for 72 hours. (1) The centrifugal pump speed should be maintained at 3 029-3 483 r/min, the flow rate was maintained at 2.24-2.60 L/min, The pressure before the pump between minus 107.57 and minus 31.86 mmHg, the pressure after the pump was 197.50-282.43 mmHg, and the pressure after the membrane was 178.71-261.5 mmHg, all were in the normal range, and there was no significant difference between different time points (all P>0.05). The performance scores of the mainframe were all 4 points or above, indicating that the use requirements were met. (2) The heart rate of the animals was 50-80 beats /min, the mean arterial pressure was 85-115 mmHg, and the lactic acid was 0.996-2.25 mmol/L, all within the normal range, and there was no significant difference between different time points (all P>0.05). The free hemoglobin was 8.98-16.39 mg/L, and the hemoglobin was 6.58-7.52 g/L, both within a reasonable range, and there was no significant difference between different time points (all P>0.05). The platelet count was 69.6-231.6×10 9/L, and showed a continuous downward trend ( P<0.05). ACT was maintained at 135-169 s, which was within the target range, and there was no significant difference between different time points ( P<0.05). (3) At the end of the experiment, there was no obvious thrombosis in the pump head and oxygenator, no obvious thrombosis or infarction in the heart, brain, liver, lung and kidney, and no obvious hemorrhage or necrosis under the microscope. Conclusions:The ECMO established by the novel domestic ECMO mainframe combined with imported membrane oxygenator and pipeline ran smoothly for 72 hours, achieving the target of effect and safety.

Objective:To design a large-scale mobile emergency resuscitation unit based on 5G communication technology to improve the efficiency of prehospital transportation and treatment.Methods:The study was conducted in Hangzhou from November 2022 to September 2023. It's sorted out the application scenario requirements for prehospital first aid, transfer, and prehospital-intrahospital emergency linkage in carrying out the program design, single technology testing, onboard debugging, and integration debugging phases sequentially.Results:In September 2023, a large-scale 5G mobile emergency resuscitation unit was completed and delivered. The unit was converted from an electric bus and consists of five parts: (1) Vehicle appearance: the vehicle is 12.9 meters long, 2.3 meters wide and 2.6 meters high, with a single mileage of 200 kilometers; (2) The overall internal structure: the vehicle has one resuscitation bed and two stretcher positions. Additionally, there is a comprehensive operating table located at the front of the vehicle. The middle of the vehicle is equipped with a central digital control screen. (3) First aid materials and instruments: the vehicle's materials are modularly configured in accordance with the resuscitation, guardianship, surgery, inspection and testing, Communication modular configuration, equipped with a defibrillation monitor, transfer ventilator, extracorporeal membrane lung oxygenation and other critical care first aid and electrocardiogram, digital radiography, blood gas analyzer, chest pain 5 monitors and other inspection and testing equipment; (4) Vehicle communication and information systems: equipped with high-definition remote video interactive system, telemedicine terminal DP300 integrated system, a real-time panoramic experience system and centralized guardianship system; (5) Vehicle disinfection: a plasma disinfector installed on the top of the car can meet the hospital disinfection hygiene standardsⅡ class environmental management requirements.Conclusions:Incorporating 5G communication technology, the large-scale mobile emergency resuscitation unit is equipped with various advanced treatment equipment and remote consultation systems. It can accommodate the resuscitation needs of the most critically ill patients, offering substantial support for public emergency rescues. Further exploration of its potential is merited.