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*

Background and Aims:Tumor deposits(TDs)may influence prognosis beyond the current 8th edition AJCC pTNM nodal classification in gastric cancer(GC).This study investigates the prognostic value of TD number and proposes an improved pN staging(mpN)that classifies patients with TD number>1 as pN3b.We validated the mpN staging against the 8th AJCC pN staging.Methods:A dual-center retrospective cohort study was performed,including 1 327 patients who underwent radical gastrectomy at Sun Yat-sen University Cancer Center(2011-2015;test cohort)and 340 patients from Guangdong Provincial People's Hospital(2015-2022;validation cohort).Patients were dichotomized into low-TD(≤1)and high-TD(>1)groups.Outcomes were overall survival(OS)and disease-free survival(DFS).Survival analyses used Kaplan-Meier curves,IPTW,and Cox regression.Predictive performance of staging systems was assessed by time-dependent ROC(tROC)/tAUC,concordance index(C-index)and Akaike information criterion(AIC).Results:TDs were present in 435/1 327(32.7%)in the test cohort.Presence of TD was associated with worse OS(IPTW-adjusted HR=2.69,95%CI=2.18-3.31,P<0.01)and DFS(HR=2.82,95%CI=2.32-3.42,P<0.01).In multivariable models,TD remained an independent adverse factor for OS(HR=1.65,95%CI=1.34-2.05;P<0.01)and DFS(HR=1.74,95%CI=1.43-2.11,P<0.01).Increasing TD number correlated with progressively poorer survival;X-tile identified>1 as an optimal cutoff,with high-TD patients showing markedly worse outcomes(OS:adjusted HR=3.65,95%CI=2.74-4.88;DFS:adjusted HR=3.74,95%CI=2.85-4.91;both P<0.01).Incorporation of TD number into the mpN staging(assigning TD>1 to pN3b)improved prognostic discrimination:in the test cohort 5-year OS tAUC was 0.746 for mpN vs.0.703 for AJCC pN(C-index 0.738 vs.0.721,AIC 5 805.27 vs.5 849.30);similar improvements were observed in the validation cohort.Conclusion:TD presence and number exert significant negative prognostic impact in GC.Classifying patients with TD number>1 as pN3b enhances prognostic accuracy.Routine reporting of TD counts and further prospective multicenter validation of mpN staging are warranted.

Objective:To analyze the value advantages of multimodal ultrasound in the diagnosis of benign and malignant nodules of 4a grade of nodules of Chinese thyroid imaging reporting and data system (C-TIRADS) of diffuse thyroid nodules. Methods:A total of 227 diffuse thyroid nodules (116 malignant nodules and 111 benign nodules) from 219 patients who admitted to Baoji Hospital Affiliated to Xi'an Medical University between January 2020 to December 2023 were retrospectively selected. Two-dimensional ultrasound and multimodal ultrasound were used to diagnose diffuse thyroid nodules,and to perform data analysis. There were 49 males and 170 females,ranging in age from 24 to 72 years old,whose average age was 52.31±10.08 years. The result of pathological diagnosis was used as the "gold standard",and the results of pathological diagnosis and the parameters of multimodal ultrasound for diffuse thyroid nodules were compared. The diagnostic efficiency of the results of multimodal ultrasound and two-dimensional ultrasound for diffuse thyroid nodules was compared and analyzed. Results:As the results of pathological diagnosis,the scores of contrast-enhanced ultrasound,micro blood flow imaging,elastography and malignant risk score of multimodal ultrasound technique of malignant diffuse thyroid nodules were significantly higher than those of benign nodules (Z=-4.258,-5.007,-5.631,P<0.05),respectively. The sensitivity (92.24％) and specificity (92.79％) of multimodal ultrasound were significantly higher than those (75.00％ and 83.78％) of two-dimensional ultrasound (x2=12.588,4.356,P<0.05),respectively. The positively predictive values (93.04％) and negatively predictive values (91.96％) of multimodal ultrasound were significantly higher than those (82.86％ and 76.23％) of two-dimensional ultrasound (x2=5.465,10.629,P<0.05),respectively. Conclusion:For the judgment of benign and malignant nodules of C-TIRADS 4a in the background of diffuse thyroid nodules,the application of multimodal ultrasound technique,especially the combined use of contrast-enhanced ultrasound,elastography and micro blood flow imaging,can greatly improve the accuracy of ultrasonic diagnosis of these diseases.

Objective:To analyze the value advantages of multimodal ultrasound in the diagnosis of benign and malignant nodules of 4a grade of nodules of Chinese thyroid imaging reporting and data system (C-TIRADS) of diffuse thyroid nodules. Methods:A total of 227 diffuse thyroid nodules (116 malignant nodules and 111 benign nodules) from 219 patients who admitted to Baoji Hospital Affiliated to Xi'an Medical University between January 2020 to December 2023 were retrospectively selected. Two-dimensional ultrasound and multimodal ultrasound were used to diagnose diffuse thyroid nodules,and to perform data analysis. There were 49 males and 170 females,ranging in age from 24 to 72 years old,whose average age was 52.31±10.08 years. The result of pathological diagnosis was used as the "gold standard",and the results of pathological diagnosis and the parameters of multimodal ultrasound for diffuse thyroid nodules were compared. The diagnostic efficiency of the results of multimodal ultrasound and two-dimensional ultrasound for diffuse thyroid nodules was compared and analyzed. Results:As the results of pathological diagnosis,the scores of contrast-enhanced ultrasound,micro blood flow imaging,elastography and malignant risk score of multimodal ultrasound technique of malignant diffuse thyroid nodules were significantly higher than those of benign nodules (Z=-4.258,-5.007,-5.631,P<0.05),respectively. The sensitivity (92.24％) and specificity (92.79％) of multimodal ultrasound were significantly higher than those (75.00％ and 83.78％) of two-dimensional ultrasound (x2=12.588,4.356,P<0.05),respectively. The positively predictive values (93.04％) and negatively predictive values (91.96％) of multimodal ultrasound were significantly higher than those (82.86％ and 76.23％) of two-dimensional ultrasound (x2=5.465,10.629,P<0.05),respectively. Conclusion:For the judgment of benign and malignant nodules of C-TIRADS 4a in the background of diffuse thyroid nodules,the application of multimodal ultrasound technique,especially the combined use of contrast-enhanced ultrasound,elastography and micro blood flow imaging,can greatly improve the accuracy of ultrasonic diagnosis of these diseases.

Objective:To investigate the application of the parameters of multimodal ultrasound elastography in differential diagnosis for thyroid nodules of patients with diffuse thyroid lesions.Methods:A total of 103 patients with diffuse thyroid lesions who underwent treatment at Affiliated Baoji Hospital of Xi′an Medical University from January 2023 to January 2024 were retrospectively selected,whose thyroid nodules were confirmed by fine needle aspiration biopsy or surgical pathology.They were grouped according to the benign or malignant nodules.56 patients with benign nodules were included in the benign nodule group,while the other 47 patients were included in the malignant nodule group.All patients were examined by conventional ultrasound and multimodal ultrasound elastography,and the relevant parameters were recorded to compare the differences between the two groups.The value of each indicator in diagnosing benign and malignant thyroid nodules was investigated.Results:There were no statistically significant differences between the benign and malignant nodule groups in terms of gender,length diameter of nodule,nodule location,functional abnormalities of thyroid,exposure history of radiation,and the presence of acoustic halos(P＞0.05),the age of patients in the malignant nodule group was lower than that of the benign nodule group(t=-3.121,P＜0.05),and the percentage of nodules with blood flow(14.89%),the percentage of aspect ratio＜1(74.47%),and the percentage of nodules with clear boundary(27.66%)in the malignant nodule group were all lower than those of the benign nodule group,with statistically significant differences(x2=25.634,5.112,12.465,P＜0.05).The ratio of lymphatic metastasis(27.66%)and that of calcification(65.96%)in the malignant nodule group were lower than those in the benign nodule group,and the differences were all statistically significant(x2=11.917,9.350,P＜0.05).The ratios of centripetal enhancement(76.60%),inhomogeneous enhancement(68.09%),low/equal enhancement(87.23%),early obvious discharge(63.83%),unclear boundary after enhancement(91.49%),and fast discharge(59.57%)in the malignant nodule group were higher than that of the benign nodule group,and the differences were statistically significant(x2=33.409,26.695,9.079,12.853,17.798,12.649,P＜0.05),respectively.The intensity and time to peak of the malignant nodule group were respectively lower and long than these of the benign nodule group,and the differences were statistically significant(t=-12.381,4.958,P＜0.05).However,the mean passage time of the two groups was not statistically significant(P＞0.05).The maximum value,minimum value and mean value of Young's modulus,the maximum value of vertical section,mean value of vertical section,maximum value of cross section,mean value of cross section in the malignant nodule group were all higher than those in the benign nodule group,and the differences were statistically significant(t=13.997,9.100,12.191,7.616,6.310,4.679,5.355,P＜0.05).The result of receiver operating characteristic(ROC)curve analysis indicated that both ultrasonography parameters and shear wave elastography(SWE)parameters had higher diagnostic value for the benign and malignant nature of thyroid nodules in patients.The area under curve(AUC)values of intensity to peak,time to peak,and the maximum value,minimum value and mean value of Young's modulus,and the maximum value of vertical section,mean value of vertical section,maximum value of cross section,mean value of cross section were respectively 0.976,0.759,0.974,0.837,0.989,0.872,0.805,0.732 and 0.749.Conclusion:Multimodal ultrasound elastography parameters has significant application value in differential diagnosis for thyroid nodules in patients with diffuse thyroid lesions.In these parameters,the diagnostic AUC values of intensity to peak,time to peak,and the maximum value and mean value of Young's modulus are higher for malignant thyroid nodules of patients,which have higher diagnostic efficiency.It can effectively help clinical doctor to accurately identify the benign and malignant nodules for patients with diffuse thyroid lesions.

Objective:To explore the application value of Superb microvascular imaging(SMI)technique in diagnosing diffuse thyroid disease with thyroid nodules,and the assessment for treatment efficacy.Methods:A total of 100 patients with diffuse thyroid disease with thyroid nodules(132 nodules),who were treated at the Baoji Hospital Affiliated to Xi'an Medical University from March 2020 to November 2024,were selected.The dual examination of SMI and conventional Color Doppler Flow Imaging(CDFI)were conducted on them.The nature of the nodules was confirmed by pathological examination.The diagnostic sensitivity,specificity and predictive value of SMI and CDFI were analyzed by using the receiver operating characteristic(ROC)curve.A series of conventional indicators,including blood flow volume,blood flow velocity,pattern of blood flow distribution,and vascular morphology,between the two imaging techniques were compared and analyzed.Results:In the 132 thyroid nodules that were detected by pathological examination,SMI identified 94 benign lesions(71.21%)and 38 malignant lesions(28.79%).The sensitivity and specificity of SMI were respectively 94.68%and 89.47%in diagnosing diffuse thyroid disease with thyroid nodules,both of them were higher than those(84.05%and 78.95%)of CDFI,and the sensitivity of SMI diagnosis was significantly higher than that of CDFI diagnosis,and the difference was statistically significant(x2=5.595,P<0.05).The nodule size as SMI diagnosis was(14.62±2.36)mm,which was significantly smaller than(16.35±4.45)mm as CDFI diagnosis,and the difference was statistically significant(x2=3.330,P<0.05).Blood flow velocity and blood flow volume of SMI diagnosis were significantly higher than those of CDFI diagnosis,and the differences were statistically significant(t=5.718,6.567,P<0.05).The detection rates of blood flow distribution mode and vascular morphology of SMI mode were significantly higher than those of CDFI mode,and the differences were statistically significant(x2=9.192,4.776,P<0.05).However,there were not statistically significant differences were observed between the two imaging techniques in terms of the shape,echo type and internal calcification of nodules(P>0.05).Conclusion:SMI technique has a significant advantage in diagnosis and assessment for diffuse thyroid disease with thyroid nodules.It can more accurately assess the hemodynamic changes of the nodules,and provide more reliable diagnostic information for clinical treatment.

Background and Aims:Tumor deposits(TDs)may influence prognosis beyond the current 8th edition AJCC pTNM nodal classification in gastric cancer(GC).This study investigates the prognostic value of TD number and proposes an improved pN staging(mpN)that classifies patients with TD number>1 as pN3b.We validated the mpN staging against the 8th AJCC pN staging.Methods:A dual-center retrospective cohort study was performed,including 1 327 patients who underwent radical gastrectomy at Sun Yat-sen University Cancer Center(2011-2015;test cohort)and 340 patients from Guangdong Provincial People's Hospital(2015-2022;validation cohort).Patients were dichotomized into low-TD(≤1)and high-TD(>1)groups.Outcomes were overall survival(OS)and disease-free survival(DFS).Survival analyses used Kaplan-Meier curves,IPTW,and Cox regression.Predictive performance of staging systems was assessed by time-dependent ROC(tROC)/tAUC,concordance index(C-index)and Akaike information criterion(AIC).Results:TDs were present in 435/1 327(32.7%)in the test cohort.Presence of TD was associated with worse OS(IPTW-adjusted HR=2.69,95%CI=2.18-3.31,P<0.01)and DFS(HR=2.82,95%CI=2.32-3.42,P<0.01).In multivariable models,TD remained an independent adverse factor for OS(HR=1.65,95%CI=1.34-2.05;P<0.01)and DFS(HR=1.74,95%CI=1.43-2.11,P<0.01).Increasing TD number correlated with progressively poorer survival;X-tile identified>1 as an optimal cutoff,with high-TD patients showing markedly worse outcomes(OS:adjusted HR=3.65,95%CI=2.74-4.88;DFS:adjusted HR=3.74,95%CI=2.85-4.91;both P<0.01).Incorporation of TD number into the mpN staging(assigning TD>1 to pN3b)improved prognostic discrimination:in the test cohort 5-year OS tAUC was 0.746 for mpN vs.0.703 for AJCC pN(C-index 0.738 vs.0.721,AIC 5 805.27 vs.5 849.30);similar improvements were observed in the validation cohort.Conclusion:TD presence and number exert significant negative prognostic impact in GC.Classifying patients with TD number>1 as pN3b enhances prognostic accuracy.Routine reporting of TD counts and further prospective multicenter validation of mpN staging are warranted.

Objective:To investigate the application of the parameters of multimodal ultrasound elastography in differential diagnosis for thyroid nodules of patients with diffuse thyroid lesions.Methods:A total of 103 patients with diffuse thyroid lesions who underwent treatment at Affiliated Baoji Hospital of Xi′an Medical University from January 2023 to January 2024 were retrospectively selected,whose thyroid nodules were confirmed by fine needle aspiration biopsy or surgical pathology.They were grouped according to the benign or malignant nodules.56 patients with benign nodules were included in the benign nodule group,while the other 47 patients were included in the malignant nodule group.All patients were examined by conventional ultrasound and multimodal ultrasound elastography,and the relevant parameters were recorded to compare the differences between the two groups.The value of each indicator in diagnosing benign and malignant thyroid nodules was investigated.Results:There were no statistically significant differences between the benign and malignant nodule groups in terms of gender,length diameter of nodule,nodule location,functional abnormalities of thyroid,exposure history of radiation,and the presence of acoustic halos(P＞0.05),the age of patients in the malignant nodule group was lower than that of the benign nodule group(t=-3.121,P＜0.05),and the percentage of nodules with blood flow(14.89%),the percentage of aspect ratio＜1(74.47%),and the percentage of nodules with clear boundary(27.66%)in the malignant nodule group were all lower than those of the benign nodule group,with statistically significant differences(x2=25.634,5.112,12.465,P＜0.05).The ratio of lymphatic metastasis(27.66%)and that of calcification(65.96%)in the malignant nodule group were lower than those in the benign nodule group,and the differences were all statistically significant(x2=11.917,9.350,P＜0.05).The ratios of centripetal enhancement(76.60%),inhomogeneous enhancement(68.09%),low/equal enhancement(87.23%),early obvious discharge(63.83%),unclear boundary after enhancement(91.49%),and fast discharge(59.57%)in the malignant nodule group were higher than that of the benign nodule group,and the differences were statistically significant(x2=33.409,26.695,9.079,12.853,17.798,12.649,P＜0.05),respectively.The intensity and time to peak of the malignant nodule group were respectively lower and long than these of the benign nodule group,and the differences were statistically significant(t=-12.381,4.958,P＜0.05).However,the mean passage time of the two groups was not statistically significant(P＞0.05).The maximum value,minimum value and mean value of Young's modulus,the maximum value of vertical section,mean value of vertical section,maximum value of cross section,mean value of cross section in the malignant nodule group were all higher than those in the benign nodule group,and the differences were statistically significant(t=13.997,9.100,12.191,7.616,6.310,4.679,5.355,P＜0.05).The result of receiver operating characteristic(ROC)curve analysis indicated that both ultrasonography parameters and shear wave elastography(SWE)parameters had higher diagnostic value for the benign and malignant nature of thyroid nodules in patients.The area under curve(AUC)values of intensity to peak,time to peak,and the maximum value,minimum value and mean value of Young's modulus,and the maximum value of vertical section,mean value of vertical section,maximum value of cross section,mean value of cross section were respectively 0.976,0.759,0.974,0.837,0.989,0.872,0.805,0.732 and 0.749.Conclusion:Multimodal ultrasound elastography parameters has significant application value in differential diagnosis for thyroid nodules in patients with diffuse thyroid lesions.In these parameters,the diagnostic AUC values of intensity to peak,time to peak,and the maximum value and mean value of Young's modulus are higher for malignant thyroid nodules of patients,which have higher diagnostic efficiency.It can effectively help clinical doctor to accurately identify the benign and malignant nodules for patients with diffuse thyroid lesions.

Objective:To explore the application value of Superb microvascular imaging(SMI)technique in diagnosing diffuse thyroid disease with thyroid nodules,and the assessment for treatment efficacy.Methods:A total of 100 patients with diffuse thyroid disease with thyroid nodules(132 nodules),who were treated at the Baoji Hospital Affiliated to Xi'an Medical University from March 2020 to November 2024,were selected.The dual examination of SMI and conventional Color Doppler Flow Imaging(CDFI)were conducted on them.The nature of the nodules was confirmed by pathological examination.The diagnostic sensitivity,specificity and predictive value of SMI and CDFI were analyzed by using the receiver operating characteristic(ROC)curve.A series of conventional indicators,including blood flow volume,blood flow velocity,pattern of blood flow distribution,and vascular morphology,between the two imaging techniques were compared and analyzed.Results:In the 132 thyroid nodules that were detected by pathological examination,SMI identified 94 benign lesions(71.21%)and 38 malignant lesions(28.79%).The sensitivity and specificity of SMI were respectively 94.68%and 89.47%in diagnosing diffuse thyroid disease with thyroid nodules,both of them were higher than those(84.05%and 78.95%)of CDFI,and the sensitivity of SMI diagnosis was significantly higher than that of CDFI diagnosis,and the difference was statistically significant(x2=5.595,P<0.05).The nodule size as SMI diagnosis was(14.62±2.36)mm,which was significantly smaller than(16.35±4.45)mm as CDFI diagnosis,and the difference was statistically significant(x2=3.330,P<0.05).Blood flow velocity and blood flow volume of SMI diagnosis were significantly higher than those of CDFI diagnosis,and the differences were statistically significant(t=5.718,6.567,P<0.05).The detection rates of blood flow distribution mode and vascular morphology of SMI mode were significantly higher than those of CDFI mode,and the differences were statistically significant(x2=9.192,4.776,P<0.05).However,there were not statistically significant differences were observed between the two imaging techniques in terms of the shape,echo type and internal calcification of nodules(P>0.05).Conclusion:SMI technique has a significant advantage in diagnosis and assessment for diffuse thyroid disease with thyroid nodules.It can more accurately assess the hemodynamic changes of the nodules,and provide more reliable diagnostic information for clinical treatment.

ObjectiveBased on spatial metabolomics technology combined with pharmacological indexes， to analyze the mechanism of Fritillariae Cirrhosae Bulbus（FCB） powder in improving bleomycin-induced pulmonary fibrosis in rats. MethodSixty SD rats were randomly divided into five groups， including the blank group， the model group， and high， medium， low dosage groups of FCB. Except for the blank group， rats in all other groups were injected with bleomycin by tracheal injection to establish a pulmonary fibrosis model. Postoperatively， the high， medium and low dosage groups of FCB were administered aqueous solutions of FCB powder at doses of 0.36， 0.18， 0.09 g·kg^-1， respectively， continuously for 28 d. The blank and model groups were given an equal volume of distilled water by gavage. After the last administration， lung tissues and blood samples were collected， the pathological conditions of rat lung tissues were comprehensively evaluated by hematoxylin-eosin（HE） and Masson staining， and aerodynamic assisted desorption electrospray ionization mass spectrometry imaging（AFADESI-MSI） was used for MSI of rat lung tissues from different experimental groups. Spatial metabolomics analysis was conducted on the fibrotic areas of lung tissues in the model group and the high dosage group of FCB based on HE staining images. Differential metabolites between groups were screened by orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） values>1， t-test P<0.05， and fold change analysis. Metabolic pathway analysis of the identified differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG）. Protein expression levels of nuclear transcription factor-κB p65（NF-κB p65） and heme oxygenase-1（HO-1） in rat lung tissues were detected by Western blot. Biochemical assessments of superoxide dismutase（SOD）， malondialdehyde（MDA） and glutathione（GSH） levels in rat lung tissues were conducted. Serum levels of interleukin（IL）-1β， IL-6， nuclear factor erythroid 2 related factor 2（Nrf2）， and tumor necrosis factor-α（TNF-α） were measured by enzyme linked immunosorbent assay（ELISA）， and some of the screened signaling pathways with strong correlation were verified. ResultThe results of MSI experiment showed that after 28 d of the administration of FCB powder to rats with pulmonary fibrosis， the content of L-arginine in the fibrotic regions of lung tissues was significantly different from that of rats in the model group， and the content of phosphatidylcholine was lower than that in the fibrotic region of lung tissues of rats in the model group. Western blot results confirmed that， in comparison to the model group， oral administration of FCB powder for 28 d could inhibit the elevated expression of NF-κB p65 protein in the lung tissues of rats with pulmonary fibrosis. Furthermore， high dose of FCB powder was able to significantly inhibit the expression of HO-1 after oral administration （P<0.05）. The cytokine detection results indicated that the concentrations of IL-1β， IL-6 and TNF-α in the serum of rats from the high， medium， low dosage groups of FCB were reduced by comparing with the model group， and the high dose of Chuanbeimu powder administered by gavage could significantly inhibit the trend of decreased SOD， GSH， Nrf2 contents and increased MDA content induced by bleomycin. ConclusionOral administration of FCB powder has the potential to partially ameliorate bleomycin-induced pulmonary fibrosis in rats， and its mechanism may be related to the regulation of pathways associated with inflammation（NF-κB p65） and oxidative stress（Nrf2/HO-1）.