BACKGROUND:Carboxylesterase 1 and inflammatory factors play a crucial role in regulating lipid metabolism and glucose homeostasis.However,the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats remain to be revealed. OBJECTIVE:To investigate the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats. METHODS:Thirty-two 8-week-old male Sprague-Dawley rats were randomly divided into normal control group(n=12)and modeling group(n=20)after 1 week of adaptive feeding.Rat models of type 2 diabetes mellitus were prepared by high-fat diet and single injection of streptozotocin.After successful modeling,the rats were randomly divided into diabetic control group(n=6),moderate-intensity exercise group(n=6)and high-intensity intermittent exercise group(n=6).The latter two groups were subjected to treadmill training at corresponding intensities,once a day,50 minutes each,and 5 days per week.Exercise intervention in each group was carried out for 6 weeks.After the intervention,ELISA was used to detect blood glucose and blood lipids of rats.The morphological changes of skeletal muscle were observed by hematoxylin-eosin staining.The mRNA expression levels of carboxylesterase 1 and inflammatory cytokines were detected by real-time quantitative PCR.The protein expression levels of carboxylesterase 1 and inflammatory cytokines were detected by western blot and immunofluorescence. RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,insulin resistance index in the diabetic control group were significantly increased(P<0.01),insulin activity was decreased(P<0.05),and the mRNA and protein levels of carboxylesterase 1,never in mitosis gene A related kinase 7(NEK7)and interleukin 18 in skeletal muscle tissue were upregulated(P<0.05).Compared with the diabetic control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,and insulin resistance index in the moderate-intensity exercise group and high-intensity intermittent exercise group were down-regulated(P<0.05),and insulin activity was increased(P<0.05).Moreover,compared with the diabetic control group,the mRNA level of NEK7 and the protein levels of carboxylesterase 1,NEK7 and interleukin 18 in skeletal muscle were decreased in the moderate-intensity exercise group(P<0.05),while the mRNA levels of carboxylesterase 1,NEK7,NOD-like receptor heat protein domain associated protein 3 and interleukin 18 and the protein levels of carboxylesterase 1 and interleukin 18 in skeletal muscle were downregulated in the high-intensity intermittent exercise group(P<0.05).Hematoxylin-eosin staining showed that compared with the diabetic control group,the cavities of myofibers in the moderate-intensity exercise group became smaller,the number of internal cavities was reduced,and the cellular structure tended to be more intact;the myocytes of rats in the high-intensity intermittent exercise group were loosely arranged,with irregular tissue shape and increased cavities in myofibers.To conclude,both moderate-intensity exercise and high-intensity intermittent exercise can reduce blood glucose,lipid,insulin resistance and carboxylesterase 1 levels in type 2 diabetic rats.Moderate-intensity exercise can significantly reduce the expression level of NEK7 protein in skeletal muscle,while high-intensity intermittent exercise can significantly reduce the expression level of interleukin 18 protein in skeletal muscle.In addition,the level of carboxylesterase 1 is closely related to the levels of NEK7 and interleukin 18.

Objective To evaluate the influence of the wearing position of dosimeters outside lead aprons on effective dose estimation for interventional radiology workers, analyze the differences between single and double dosimeter methods in effective dose estimation, and provide a reference for the personal dose monitoring of interventional radiology workers. Methods This study employed a combined approach of on-site monitoring and Monte Carlo simulation to evaluate the impact of the wearing position of dosimeters outside lead aprons on effective dose estimation, as well as the differences between effective doses measured using single and double dosimeters. Interventional radiology workers wore dosimeters at three positions: the neck outside the lead collar, the left chest outside the lead apron, and inside the lead apron. Effective doses were estimated using the single and double dosimeter methods specified in GBZ 128-2019 Specifications for individual monitoring of occupational external exposure, and the impact of different wearing positions on the estimation results was compared. Geant4 Monte Carlo simulations were used to model dose distributions at the neck outside the lead collar and at the left chest outside the lead apron for operators performing cardiovascular interventions under tube voltages of 70, 80, 90, and 100 kVp and exposure angles of posteroanterior (PA), anteroposterior (AP), and left anterior oblique 45° (LAO45°) positions. The study assessed the impact of dosimeter wearing position on effective dose estimation. Results Monte Carlo simulations demonstrated that neck doses consistently exceeded left chest doses across different tube voltages and exposure angles, with neck-to-chest dose ratios of 0.80-0.90. Under identical tube voltage conditions, AP showed the highest doses, followed by LAO45°, and PA demonstrated the lowest doses. The single and double dosimeter methods exhibited consistent patterns in effective dose estimation. Single dosimeter method generally yielded higher effective doses with relative deviations of 9.9% to 83%, though these deviations decreased under high tube voltages. Field monitoring data indicated that most interventional radiology workers maintained relative deviations between single and double dosimeter calculations below 6%, with neck-to-chest dose ratios of 0.95-1.1. The estimation patterns remained consistent across both methods, though single dosimeter method showed slightly higher results. Conclusion Under PA, AP, or LAO45°, the doses at the neck consistently exceeded those at the left chest. Therefore, when wearing lead protective equipment, the dosimeter should be properly positioned at the neck outside the lead collar to accurately reflect the radiation doses of surgeons. Some interventional radiology workers improperly positioned the dosimeter (intended at the neck outside the lead collar) at the left chest outside the lead apron, and this may result in an underestimation of the effective dose.

OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

Objective To explore the integration value of mobile virtual reality devices in the classroom teaching of human anatomy,and to evaluate their potential impact on the in-depth construction of human anatomy knowledge,the cultivation of spatial cognitive ability,and the transformation of teaching paradigms from the perspectives of cognitive load theory and situated learning.Methods The undergraduate students majoring in clinical medicine in Peking University were selected as the research objects.Among them,students in grade 2019 were the control group,and students in grade 2022 were the experimental group,introducing movable virtual anatomy equipment and other teaching auxiliary method in theory and practice courses.The final exam scores of the two groups of students were compared,and a questionnaire survey was conducted for the experimental group after the course,and the survey result were statistically analyzed.Results The final examination result showed that the average score of the experimental group was 82.47±10.19,and the average score of the control group was 74.82±16.56,which was significantly higher in the experimental group than in the control group,with statistical significance(P＜0.05).The questionnaire survey result showed that compared with traditional classroom teaching,94.62％of students preferred the new auxiliary teaching mode such as VR,96.77％of students believed that VR assisted teaching could achieve the traditional teaching effect or better,95.7％of them think that it improved students' interest in learning human anatomy,and 98.92％thought that it improved students' knowledge of anatomy.Conclusion The application of mobile virtual reality devices in anatomy classroom teaching provides immersive and interactive 3D visualization teaching scenarios,effectively reducing students' cognitive load on abstract and complex anatomical structures,promoting spatial understanding and knowledge internalization,significantly improving teaching effectiveness and self-learning ability,thus changing the traditional anatomy teaching mode and laying a solid foundation for the development of future medical education and the cultivation of medical talents.

Objective:To investigate the curative effect and mechanism of hyperbaric oxygen therapy on nonalcoholic fatty liver disease in mice.Methods:Twenty-one 8-week-old male C57BL/6J mice were divided into three groups: control group (normal diet), model group (high-fat and high-cholesterol diet), and hyperbaric oxygen group (high-fat and high-cholesterol diet + hyperbaric oxygen therapy), with seven mice in each group. The changes in body weight, serum liver enzymes, and blood lipids were compared after treatment between the three groups. Hematoxylin-eosin staining, Oil Red O staining, Sirius red staining, and F4/80 immunohistochemical staining were used to observe the pathological changes in liver tissues. RT-qPCR and Western blot methods were used to detect the expression levels of oxidative stress and inflammatory factors. One-way analysis of variance was used for comparison among the groups.Results:Mice in the hyperbaric oxygen group had significantly improved liver histopathology. The serological levels of alanine aminotransferase, aspartate aminotransferase, and cholesterol were (77.50±13.59) U/L, (156.06±23.68) U/L, and (4.80±0.53) mmol/L, which were significantly lower than those in the model group [(109.43±16.88) U/L, (216.62±18.79) U/L, and (5.86±0.53) mmol/L, P<0.05], and accompanied by lower levels of lipid deposition, macrophage infiltration, and fibrosis. In addition, compared with the model group, the expression of antioxidant stress protein nuclear transcription factor erythroid 2-related factor 2 [(0.30±0.06) and (2.16±1.21), P<0.05] and heme oxygenase-1 [(0.48±0.19) and (1.01±0.18), P<0.05] in liver tissue showed an upward trend following hyperbaric oxygen treatment, which was also validated at the transcriptional level ( P<0.05). Simultaneously, compared with the model group, the mRNA expressions of tumor necrosis factor-α [(2.60±0.71) and (0.66±0.15), P<0.05], interleukin-1β [(2.41±1.01) and (0.78±0.23), P<0.05], and interleukin-6 [(3.61±2.17) and (0.94±0.25), P<0.05] in the liver tissue of mice in the hyperbaric oxygen group were decreased. The tumor necrosis factor-α protein level [(7.50±4.73) and (1.05±0.58), P<0.05] and interleukin-1β [(1.65±0.35) and (1.02±0.02), P<0.05] was reduced following hyperbaric oxygen treatment compared with those in the model group. Conclusion:Hyperbaric oxygen therapy can slow down the progression of nonalcoholic fatty liver disease by regulating the levels of oxidative stress and inflammation in the mice.

Objective:To investigate the efficacy and safety of ablation index-guided radiofrequency catheter ablation (RFCA) and second-generation cryoballoon ablation (CBA) in elderly patients with atrial fibrillation (AF).Methods:This retrospective cohort study included 1 986 patients undergoing pulmonary vein isolation for AF at General Hospital of Northern Theater Command from August 2016 to May 2020, comprising 760 RFCA cases and 1 226 CBA cases. Elderly patients were defined as those aged 60 years or older, while non-elderly patients were those under 60 years of age. All patients were followed up for 3 years after the procedure to assess AF recurrence rates. Kaplan-Meier survival curves were plotted and compared by log-rank test. Multivariate logistic regression was used to analyze the influencing factors of AF recurrence.Results:Among 1 986 AF patients (aged (58.7±10.2) years; 1 307 males, 65.81%; 987 elderly patients, 49.70%), the overall AF recurrence rate was 24.37% (484/1 986). Kaplan-Meier analysis demonstrated a higher AF recurrence rate in the elderly group compared to the non-elderly group (log-rank P=0.007). In the RFCA group, AF recurrence rate was 22.50% (171/760), with no significant difference between the elderly (24.44%, 88/360) and non-elderly (20.75%, 83/400) subgroups ( P=0.223). In the CBA group, recurrence rates were 25.53% (313/1 226), with significantly higher recurrence in elderly patients (28.55%, 179/627) than non-elderly (22.37%, 134/599) ( P=0.013). Multivariate logistic regression analysis revealed that advanced age was not an independent predictor of AF recurrence ( P=0.447). Longer AF duration and larger left atrial diameter were independent risk factors for recurrence, while male sex was a protective factor (all P<0.05). Conclusion:Pulmonary vein isolation with second-generation CBA and RFCA guided by ablation index are safe and effective in the treatment of AF in elderly patients.

BACKGROUND:Activation of nuclear factor-κB/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling leads to endothelial dysfunction,oxidative stress,and plays a key role in the initiation of lipid metabolism disorders and arteriosclerosis.However,currenty,the effect of walnut oil and peanut oil on skeletal muscle inflammatory factors in arteriosclerotic rats remains unclear.OBJECTIVE:To discuss the effect and mechanism of walnut oil and peanut oil on atherosclerosis.METHODS:Forty 8-week-old SD male rats were randomly divided into normal control group(n=10)and high fat group(n=30)after 1 week of adaptive feeding.The atherosclerosis model was established by high-fat diet combined with vitamin D3 injection.The rats with successful modeling were randomly divided into model group(n=10),peanut oil group(n=8)and walnut oil group(n=8).The latter two groups were gavaged with peanut oil or walnut oil for 4 weeks(5 days/week,1.2 g/kg per day).After the intervention,ELISA was used to detect the related indexes of blood lipids in rats.The morphological changes of aorta were observed by hematoxylin-eosin staining.The RT-qPCR and western blot assay were used to detect nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,interleukin-18 mRNA and nuclear factor-κB,NLRP3,interleukin-1β protein expression levels in skeletal muscle.The protein expressions of nuclear factor-κB and NLRP3 were detected by immunofluorescence immunohistochemical staining.RESULTS AND CONCLUSION:(1)Compared with the normal control group,the aortic wall of rats in the model group was thickened,the damage and lipid precipitation were more serious,the blood lipid levels and arteriosclerosis index were significantly increased(P＜0.01).The mRNA levels of nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,and interleukin-18,and the protein expressions of nuclear factor-κB,NLRP3,and interleukin-1β in skeletal muscle were significantly increased(P＜0.01).(2)Compared with model group,the vulnerable area of aortic tissue in peanut oil group and walnut oil group was significantly reduced,the levels of total cholesterol,triglyceride,low density lipoprotein cholesterol in serum,and atherosclerosis index were decreased(P＜0.01),and the mRNA expressions of nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,and interleukin-18 and the protein expressions of nuclear factor-κB,NLRP3,and interleukin-1β in skeletal muscle were significantly decreased(P＜0.01 or P＜0.05).(3)Compared with peanut oil group,the serum total cholesterol,triglyceride,and low density lipoprotein cholesterol levels in walnut oil group were significantly decreased(P＜0.01 or P＜0.05),and the mRNA levels of nuclear factor-κB,NLRP3,Caspase-1,interleukin-18,and the protein levels of nuclear factor-κB,NLRP3,interleukin-1β decreased significantly in skeletal muscle(P＜0.01 or P＜0.05).It is concluded that both peanut oil and walnut oil have ameliorative effect on atherosclerotic damage,which may be related to nuclear factor-κB/NLRP3 signaling pathway,and walnut oil has better ameliorative effect than peanut oil.

Objective:To evaluate the efficacy and safety of blinatumomab in adult patients with relapsed/refractory(R/R)or measurable residual disease(MRD)positive B-cell acute lymphoblastic leukemia(B-ALL)in the real world.Methods:The clinical data of 30 B-ALL patients received at least 1 course of blinatumomab therapy in the Chinese PLA General Hospital from January 1st,2021 to December 31st,2023 were retrospectively analyzed,including pre-treatment baseline clinical feature,post-treatment complete response(CR),CR with partial hematologic recovery(CRh),CR with incomplete hematologic recovery(CRi),complete MRD response rate,MRD response rate(MRD＜10-4),overall survival(OS),and disease-free survival(DFS),as well as drug-related adverse reactions.Results:Among 5 patients who were not assessed 4 were MRD negative and 1 did not receive bone marrow biopsy.In the R/R B-ALL group(13 cases),11 patients achieved CR/CRh/CRi and 10 patients achieved complete MRD response.In MRD+group(12 cases),9 patients achieved overall MRD response and 7 patients achieved complete MRD response.The median follow-up time was 8.4(95％CI:6.3-10.4)months.The median OS was 15.5(95％CI:0.7-30.3)months in the R/R group,while not reached in the MRD+group.The median DFS of the two groups were not reached.Drug-related adverse reactions occurred in 22 patients,and pyrexia was the most common(13 cases).Grade ≥3 adverse reactions occurred in 15 patients,and neutropenia was the most common(9 cases).Cytokine release syndrome occurred in 6 patients,including 5 cases with grade 1 and 1 case with grade 3.No patients interrupted therapy or died due to drug-related adverse reactions.Conclusion:Blinatumomab is effective in the treatment of R/R or continuous MRD+B-ALL with acceptable adverse reactions.

We reported the clinical,imaging,and treatment process of a patient with severe cranial penetrating injury caused by a nail from a nail gun that accidentally shot into the eye and penetrated into the skull while working.The patient was admitted to the Qingpu Branch of Zhongshan Hospital,Fudan University after being injured by the nail gun.The patient was admitted to the hospital 1 hour after injury with coma.After admission,the foreign body was completely removed and part of the hematoma was cleared through emergency surgery.After surgery,there were high-risk complications such as cerebral edema peak,intracranial hypertension,intracranial infection,cerebrospinal fluid leakage,and intracranial pseudoaneurysm.The patient eventually regained consciousness and was transferred to rehabilitation treatment.