The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.
Humans ; Extracellular Vesicles/physiology* ; Oocytes/cytology* ; Female ; Animals ; Cell Communication/physiology*

In this comprehensive review, we delve into the evolution of drug delivery systems in reproductive medicine with a focus on the emerging role of exosomes, a class of extracellular vesicles. Exosomes offer unique advantages in overcoming these challenges due to their inherent biocompatibility, stability, and ability to facilitate targeted delivery. This review provides a detailed examination of exosome biogenesis and their function in cellular communication, setting the stage for understanding their potential as drug delivery vehicles. We explore the mechanisms through which exosomes can be loaded with small molecule drugs and the benefits they offer over synthetic nanoparticles. The review highlights groundbreaking case studies that illustrate the successful application of exosome-mediated drug delivery in reproductive health, including enhancing fertility treatments, supporting gamete and embryo development, and facilitating maternal-fetal communication. This study aims to provide a precise understanding of how exosomal drug delivery can revolutionize treatments for reproductive health disorders, paving the way for future therapeutic applications. Lastly, we touch upon the promising therapeutic implications of exosomal delivery for proteins and genes, offering a window into future treatments for reproductive health disorders.

Objective To screen the independent influencing factors for gastrointestinal bleeding(GIB)in hospitalized patients with coronary heart disease(CHD)and to construct and validate a no-mogram prediction model.Methods A total of 440 CHD patients who developed GIB during hospi-talization were selected as GIB group,and another 320 CHD patients hospitalized in the department of cardiovascular medicine were randomly selected as non-GIB group.The clinical data of the two groups were analyzed and compared.Multivariate logistic regression analysis was used to screen the indepen-dentinfluencing factors for GIB.Based on these factors,a nomogram prediction model for the risk of GIB in hospitalized CHD patients was constructed.The entire dataset was randomly divided into train-ing set(n=532)and validation set(n=228)in a 7∶3 ratio.The performance of the nomogram model was evaluated using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results Multivariate logistic regression analysis showed that body mass index(BMI),history of digestive system diseases,CHD classification,albumin,white blood cell count,monocyte-to-lymphocyte ratio(MLR),and low-density lipoprotein were all independent influencing factors for GIB in CHD patients(P＜0.05).ROC curve analysis indicated that the nomo-gram model(excluding low-density lipoprotein)constructed based on independent influencing factors exhibited good discrimination in both the training set(area under the curve:0.839,95％CI,0.805 to 0.873)and the validation set(area under the curve:0.810,95％CI,0.751 to 0.868).Calibration curve analysis demonstrated good consistency between the predicted probabilities and the observed incidence of GIB in hospitalized CHD patients in both the training and validation sets.DCA results revealed that the nomogram model had a good clinical net benefit.Conclusion The nomogram model constructed based on independent influencing factors has good predictive performance for the risk of GIB in hospitalized CHD patients and can provide a basis for clinicians to promptly identify GIB and adjust medication regimens.

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg^-1） groups， and a trimetazidine group （0.002 g·kg^-1）. By intragastric administration of vitamin D₃ and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.

Objective To investigate the predictive efficacy of serum aminoterminal brain natriuretic pep-tide precursor(NT-proBNP),hypersensitive C-reactive protein(hs-CRP),D-dimer(D-D)and procalcitonin(PCT)in heart failure after acute myocardial infarction(AMI),Methods A total of 100 AMI patients admit-ted to the hospital from July 2021 to July 2023 were enrolled in the study as the observation group,In addi-tion,100 healthy people who underwent physical examination in the hospital during the same period were en-rolled as the control group,The serum levels of NT-proBNP,hs-CRP,D-D and PCT were detected and com-pared between the observation group and the control group,The AMI patients enrolled in the study were fur-ther divided into the heart failure group(31 cases)and the non-heart failure group(69 cases)according to the presence or absence of heart failure.The serum levels of NT-proBNP,hs-CRP,D-D,and PCT were compared between the two groups,Univariate analysis and multivariate Logistic regression analysis were used to analyze the risk factors of heart failure after AMI,Receiver operating characteristic(ROC)curve and decision curve a-nalysis(DCA)were used to analyze the predictive efficacy of serum NT-proBNP,hs-CRP,D-D and PCT for heart failure after AMI.Results The levels of serum NT-proBNP,hs-CRP,D-D and PCT in the observation group were higher than those in the control group(P＜0.05).The serum levels of NT-proBNP,hs-CRP,D-D and PCT in the complicated heart failure group were higher than those in the non-heart failure group(P＜0.05),Body mass index(BMI),smoking history,hypertension,number of diseased vessels,serum uric acid(SUA),low-density lipoprotein cholesterol(LDL-C),NT-proBNP,hs-CRP,D-D and PCT were risk factors for heart failure after AMI(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of combined detection of serum NT-proBNP,hs-CRP,D-D and PCT for predicting heart failure after AMI was 0.857(95％CI:0.811-0.948),the sensitivity was 96.12％,and the specificity was 91.28％,which were higher than the corresponding efficacy indexes of single detection(P＜0.05).DCA analysis showed that when the high-risk threshold was 0-0.99,the net benefit rate was greater than 0,which had clinical significance,When the threshold was 0-0.76,the net benefit rate of combined detection of serum NT-proBNP,hs-CRP,D-D and PCT was better than that of serum NT-proBNP,hs-CRP,D-D and PCT alone.Conclusion Combined detection of serum NT-proBNP,hs-CRP,D-D and PCT can improve the predictive efficiency of AMI compli-cated with heart failure,BMI,smoking history,hypertension,number of diseased vessels,SUA,LDL-C,NT-proBNP,hs-CRP,D-D and PCT are risk factors for AMI complicated with heart failure.

Objective:To investigate the effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride (GelMA) hydrogel (hereinafter referred to as composite hydrogel) in the repair of infected full-thickness skin defect wounds in mice.Methods:This study was an experimental study. Cerium oxide nanoenzyme with a particle size of (116±9) nm was prepared by hydrothermal method, and GelMA hydrogel with porous network structure and good gelling performance was also prepared. The 25 μg/mL cerium oxide nanoenzyme which could significantly promote the proliferation of human skin fibroblasts and had high superoxide dismutase activity was screened out. It was added to GelMA hydrogel to prepare composite hydrogel. The percentage of cerium oxide nanoenzyme released from the composite hydrogel was calculated after immersing it in phosphate buffer solution (PBS) for 3 and 7 d. The red blood cell suspension of mice was divided into PBS group, Triton X-100 group, cerium oxide nanoenzyme group, GelMA hydrogel group, and composite hydrogel group, which were treated with corresponding solution. The hemolysis of red blood cells was detected by microplate reader after 1 h of treatment. The bacterial concentrations of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were determined after being cultured with PBS, cerium oxide nanoenzyme, GelMA hydrogel, and composite hydrogel for 2 h. The sample size in all above experiments was 3. Twenty-four 8-week-old male BALB/c mice were taken, and a full-thickness skin defect wound was prepared in the symmetrical position on the back and infected with MRSA. The mice were divided into control group without any drug intervention, and cerium oxide nanoenzyme group, GelMA hydrogel group, and composite hydrogel group applied with corresponding solution, with 6 mice in each group. The wound healing was observed on 3, 7, and 14 d after injury, and the remaining wound areas on 3 and 7 d after injury were measured (the sample size was 5). The concentration of MRSA in the wound exudation of mice on 3 d after injury was measured (the sample size was 3), and the blood flow perfusion in the wound of mice on 5 d after injury was observed using a laser speckle flow imaging system (the sample size was 6). On 14 d after injury, the wound tissue of mice was collected for hematoxylin-eosin staining to observe the newly formed epithelium and for Masson staining to observe the collagen situation (the sample size was both 3). Results:After immersion for 3 and 7 d, the release percentages of cerium oxide nanoenzyme in the composite hydrogel were about 39% and 75%, respectively. After 1 h of treatment, compared with that in Triton X-100 group, the hemolysis of red blood cells in PBS group, GelMA hydrogel group, cerium oxide nanoenzyme group, and composite hydrogel group was significantly decreased ( P<0.05). Compared with that cultured with PBS, the concentrations of MRSA and Escherichia coli cultured with cerium oxide nanoenzyme, GelMA hydrogel, and composite hydrogel for 2 h were significantly decreased ( P<0.05). The wounds of mice in the four groups were gradually healed from 3 to 14 d after injury, and the wounds of mice in composite hydrogel group were all healed on 14 d after injury. On 3 and 7 d after injury, the remaining wound areas of mice in composite hydrogel group were (29±3) and (13±5) mm 2, respectively, which were significantly smaller than (56±12) and (46±10) mm 2 in control group and (51±7) and (38±8) mm 2 in cerium oxide nanoenzyme group (with P values all <0.05), but was similar to (41±5) and (24±9) mm 2 in GelMA hydrogel group (with P values both >0.05). On 3 d after injury, the concentration of MRSA on the wound of mice in composite hydrogel group was significantly lower than that in control group, cerium oxide nanoenzyme group, and GelMA hydrogel group, respectively (with P values all <0.05). On 5 d after injury, the volume of blood perfusion in the wound of mice in composite hydrogel group was significantly higher than that in control group, cerium oxide nanoenzyme group, and GelMA hydrogel group, respectively ( P<0.05). On 14 d after injury, the wound of mice in composite hydrogel group basically completed epithelization, and the epithelization was significantly better than that in the other three groups. Compared with that in the other three groups, the content of collagen in the wound of mice in composite hydrogel group was significantly increased, and the arrangement was also more orderly. Conclusions:The composite hydrogel has good biocompatibility and antibacterial effect in vivo and in vitro. It can continuously sustained release cerium oxide nanoenzyme, improve wound blood perfusion in the early stage, and promote wound re-epithelialization and collagen synthesis, therefore promoting the healing of infected full-thickness skin defect wounds in mice.

Objective:To explore the effectiveness of a hysteroscopic endometrial lesion diagnosis model de-veloped based on deep learning(DL)algorithm combined with gradient-weighted class activation mapping(Grad-CAM)visualization technology.Methods:303 hysteroscopy videos(4781 images)of 291 patients who un-derwent hysteroscopy examination in the Department of Gynecology,Renmin Hospital of Wuhan University from June 1,2021 to December 31,2022 were selected.The dataset was divided into a training set(3703 images)and a test set(1078 images)by weight sampling method.After the training set was used for model learning and train-ing,two model architectures,residual neural network(ResNet18)and efficient neural network(EfficientNet-B0),were selected to verify the model in the test set by five-class and two-class classification tasks,respectively.Tak-ing histopathology as the gold standard,the diagnostic efficacy was evaluated to select the optimal model,and the Grad-CAM layer was embedded in the optimal model to output hysteroscopy images of Grad-CAM.Results:①In the five-class classification tasks,the accuracy of EfficientNet-B0 model(93.23％)was higher than that of Res-Net18 model(84.23％);the area under the curve(AUC)of EfficientNet-B0 model in the diagnosis of five disea-ses,including atypical endometrial hyperplasia,endometrial polyps,endometrial cancer,endometrial atypical hy-perplasia,and submucous myoma,was slightly higher than that of ResNet18 model,and the AUC of both models was almost above 0.980.②In the binary classification task of accuracy and the evaluation of specificity,the two models were similar,both above 93.00％,and the sensitivity of EfficientNet-B0 model(91.14％)was significantly better than that of ResNet18 model(77.22％).③EfficientNet-B0 model combined with Grad-CAM algorithm could identify the abnormal areas in the image.After biopsy and pathological examination,it was confirmed that about 95％of the marked areas in the model's output heatmap were lesion areas.Conclusions:The hysteroscopy di-agnostic model developed by EfficientNet-B0 model combined with Grad-CAM has high diagnostic accuracy,sen-sitivity,and specificity,and has application value in the diagnosis of endometrial lesions.

Objective To achieve personalized assessment of cumulated activity distribution in patients undergoing 18F-FDG PET scans using the biokinetic model based on the single-time-point PET images.Methods A biokinetic compartmental model for the organs of interest was established,and the variation of activities in each compartment was described as a set of differential equations.The PET image data at a specific time point of each patient was used to obtain the kinetic model parameters which were then optimized by a simulated annealing algorithm to calculate the cumulated activity of each organ.Additionally,the effects of different voiding patterns on the cumulated activity of the bladder were analyzed.Considering the heterogeneity of radioactive nuclide distribution in organs,a whole-body cumulated activity distribution map was computed,and the accuracy of the proposed method was evaluated by comparison with the existing methods.Results For the 11 cases analyzed in the study,the calculation results of the biokinetic model generally showed a good agreement with experimental data,with an average deviation of less than 15%.Meanwhile,under different urinary excretion conditions,the average cumulated activity in the bladder differed by up to 2.4 times,indicating the positive significance of enforced urination in reducing radiation exposure.The comparison with the biokinetic data obtained from ICRP Publication 128 revealed relatively large deviations for certain organs such as the brain and heart,with standard deviations of 61.0%and 46.3%,respectively.Conclusion The constructed biokinetic model can effectively estimate the individualized cumulated activity distribution in patients undergoing PET scans,providing valuable insights for the internal dosimetry assessment.

Objective:To investigate the incidence and prothrombotic risk factors of postoperative venous thromboembolism(VTE) in Cushing′s disease and to further develop an assessment model to identify those at high risk of postoperative VTE events.Methods:A retrospective study was performed in 82 patients who were admitted to Huashan Hospital, Fudan University during January 2019 and January 2020 and diagnosed with Cushing′s disease. These patients underwent the evaluation about their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. The least absolute shrinkage and selection operator(LASSO) regression analysis was used to screen independent risk factors, and a nomogram model for postsurgical VTE risk assessment in Cushing′s disease was initially established, and Bootstrap method was used for internal verification. Finally, the predictive model was evaluated for calibration and clinical applicability in the study cohort.Results:Nineteen patients(23.17%) developed VTE events, with 14 cases occurring after endoscopic transsphenoidal surgery. Compared to patients without VTE, those in the VTE group were older( P<0.001), had longer postoperative bed rest, higher rates of current infection, higher HbA 1C levels, and more severe glucose tolerance impairment(all P<0.05). Through LASSO regression analysis, two independent risk factors for postoperative VTE were identified: Age and current infection. Then a VTE risk assessment nomogram model was established to predict the patients at high risk of VTE. In the nomogram model for VTE risk assessment, the area under the receiver operating characteristic curve was 0.868(95% CI 0.787-0.949), with the calibration curve closely aligning with the ideal diagonal line and the clinical decision curve exceeding the two extreme curves. Conclusions:Advanced perioperative assessment needs to be taken to screen those with high VTE risks in patients diagnosed with Cushing′s disease. Additionally, during the perioperative period, patients with Cushing′s disease should undergo mandatory physical activity or prophylactic anticoagulant therapy.