Objective:To compare the efficacy of dienogest (DNG) and levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of intrinsic and extrinsic subtypes of adenomyosis.Methods:Totally 232 patients were enrolled in the study who were diagnosed as adenomyosis by ultrasound or pelvic magnetic resonance imaging (MRI), and were classified into intrinsic and extrinsic subtypes according to different locations of lesions in MRI, treated with DNG (DNG group) or LNG-IUS (LNG-IUS group) in Peking University Third Hospital from July 2019 to December 2023. Clinical data of patients were retrospectively collected to analyze the clinical and imaging characteristics of different MRI subtypes of adenomyosis and whether there were differences in the therapeutic effects of DNG and LNG-IUS.Results:(1) Among the 232 patients enrolled, 129 were intrinsic subtype and 103 were extrinsic subtype. Among the 129 patients treated with DNG, the numbers of intrinsic and extrinsic subtype were 69 and 60, respectively. And among the 103 patients treated with LNG-IUS, the numbers of intrinsic and extrinsic subtype were 60 and 43, respectively. The mean age in DNG group [(37.5±5.6) years] was lower than that in LNG-IUS group [(40.3±4.3) years, P<0.001]. There were no significant differences in other clinical features (all P>0.05). (2) The visual analog scale (VAS) scores of dysmenorrhea and cancer antigen 125 (CA 125) levels in DNG group and LNG-IUS group were significantly decreased after treatment (all P<0.001), and hemoglobin levels were increased (both P<0.01). Compared between the two groups, the VAS score after treatment was lower in DNG group ( P<0.001), and the hemoglobin level was increased more significantly in DNG group ( P=0.016). The complete remission rates of dysmenorrhea in DNG group and LNG-IUS group were 73.0% (89/122) and 29.5% (28/95), respectively ( P=0.039). The incidence of irregular bleeding in DNG group was higher than LNG-IUS group, but there was no statistical significance [62.8% (81/129) vs 52.4% (54/103), P=0.112]. (3) Among patients with intrinsic adenomyosis, the incidence of menorrhagia was significantly higher than in those with extrinsic adenomyosis ( P<0.001), while the incidence and severity of dysmenorrhea were lower compared to extrinsic adenomyosis ( P=0.004, P=0.007, respectively). After treatment with DNG and LNG-IUS, there were no statistically significant differences in VAS scores between patients with intrinsic and extrinsic adenomyosis (all P>0.05). The incidence of irregular bleeding after DNG treatment was 78.3% (54/69) in intrinsic adenomyosis, which was higher than the 45.0% (27/60) observed in extrinsic adenomyosis ( P<0.01). Similarly, the incidence of irregular bleeding after LNG-IUS treatment was 63.3% (38/60) in intrinsic adenomyosis, higher than the 37.2% (16/43) in extrinsic adenomyosis ( P=0.009). (4) DNG treatment ( OR=19.163, 95% CI: 7.564-48.544; P<0.01) and duration of treatment ( OR=1.043, 95% CI: 1.012-1.075; P=0.007) were independent positive factors for complete remission of dysmenorrhea, while VAS score before treatment ( OR=0.654, 95% CI: 0.454-0.942; P=0.023) was negative factor. Intrinsic subtype was an independent risk factor for irregular bleeding ( OR=0.436, 95% CI: 0.235-0.811; P=0.009). Conclusions:DNG demonstrates greater advantages over LNG-IUS in terms of complete relief of dysmenorrhea and the degree of symptom alleviation. The incidence of irregular vaginal bleeding in patients with intrinsic adenomyosis is higher than in those with extrinsic adenomyosis. For patients with extrinsic adenomyosis, particularly those with prominent dysmenorrhea symptoms, DNG treatment offers greater benefits. However, for patients with intrinsic adenomyosis and those with significant menstrual disorders, a more cautious approach is required when selecting progestin therapy, along with enhanced monitoring and management.

Objective:To analyze the differences in the clinical characteristics of patients with adenomyosis of different magnetic resonance imaging (MRI) types and the differences in treatment effects after the application of dienogest.Methods:A total of 176 patients with adenomyosis who were admitted to Peking University Third Hospital from June 2017 to February 2023 were included in the study, and all of them were clearly classified by pelvic MRI and treated with dienogest. The clinical characteristics and treatment of the patients were retrospectively collected, and the patients were divided into endogenous type, exogenous type and penetrating type by MRI. The differences in clinical symptoms, imaging features and treatment effect of patients with adenomyosis of different MRI types were analyzed.Results:(1) The percentages of patients with endogenous, exogenous, and penetrating types were 40.9% (72/176), 35.2% (62/176) and 23.9% (42/176), respectively. The proportion of dysmenorrhea in patients with endogenous type (90.3%, 65/72) was significantly lower than those of exogenous type (100.0%, 62/62) and penetrating type (97.6%, 41/42; χ2=7.853, P=0.020), while there was no significant difference between exogenous type and penetrating type ( P>0.05). There were no statistically significant differences in menarche time, menstrual cycle and menstrual period among the three types of patients (all P>0.05), there was also no statistically significant difference in the proportion of menstrual abnormalities (including heavy and irregular menstrual bleeding; P>0.05). The proportions of ovarian endometrioma and deep infiltrating endometriosis in exogenous and penetrating types were significantly higher than that in endogenous type (all P<0.05). (2) The pain scores of all patients were significantly lower than those before treatment (all P<0.001), the proportion of patients with exogenous type (62.9%, 39/62) who had complete remission after treatment was higher than those of endogenous type (49.2%, 32/65) and penetrating type (46.3%, 19/41), but there was no significant difference in pain relief (i.e. the variation in the pain scores) between the three types ( P>0.05). (3) Endogenous type ( OR=0.361, 95% CI: 0.147-0.883; P=0.026), failure to apply gonadotropin-releasing hormone agonist (GnRH-a) in advance ( OR=0.208, 95% CI: 0.083-0.518; P<0.001), cystic changes ( OR=2.671, 95% CI: 1.108-6.437; P=0.029) and abnormal menstruation ( OR=3.466, 95% CI: 1.464-8.209; P=0.005) were independent risk factors for irregular bleeding after dienogest treatment. Conclusions:(1) There are obvious differences in the clinical characteristics of patients with adenomyosis of different MRI types, and patients with exogenous and penetrating types are more likely to have dysmenorrhea symptoms. (2) Dienogest could significantly alleviate the symptoms of dysmenorrhea in patients with adenomyosis. (3) Endogenous type, failure to take GnRH-a in advance and associated menstrual abnormalities are independent risk factors for irregular bleeding after dienogest treatment.

Objective To compare the therapeutic efficacy of sequential therapy with gonadotropin releasing hormone agonist(GnRH-a)combined with dienogest(DNG)versus DNG alone in patients with adenomyosis.Methods A retrospective analysis was conducted on clinical data from 129 patients diagnosed with adenomyosis by ultrasound and MRI between August 2020 and December 2023.Among them,60 patients received sequential therapy with GnRH-a followed by DNG(combination group)and 69 patients received DNG monotherapy(monotherapy group).There were no significant differences in baseline characteristics,including age,incidence of dysmenorrhea,incidence of menorrhagia,uterine volume,and type of adenomyosis between the two groups(P>0.05).The combination group received subcutaneous injections of leuprorelin3.75 mg every28 d for3 to 6 cycles,followed by oral DNG 2 mg/d for more than 3 months.The monotherapy group received oral DNG 2 mg/d alone for more than 3 months.Treatment outcomes and adverse reactions were compared between the two groups.Results The median duration of DNG treatment was 16.0(10.2,26.0)months in the combination group and13.0(6.0,23.0)months in the monotherapy group.The difference between the two groups was not statistically significant(Z=-1.587,P=0.113).Both groups showed a significant reduction in dysmenorrhea as measured by the Visual Analogue Scale(VAS)score,a significant decrease in serum CA125 levels,and a significant increase in hemoglobin levels after treatment compared to before treatment(all P<0.001).There were no significant differences between the two groups(P>0.05).Regarding uterine volume,the combination group showed a trend toward reduction after treatment[146.3(77.6,250.4)cm3 vs.118.4(82.4,233.4)cm3,Z=0.272,P=0.785],while the monotherapy group showed a significant increase in uterine volume compared to before treatment[162.9(110.8,256.0)cm3 vs.187.6(123.7,276.2)cm3,Z=2.945,P=0.003].The incidence of irregular vaginal bleeding in the combination group[50.0%(30/60)]was lower than that in the monotherapy group[75.4%(52/69),χ2=8.914,P=0.003].Conclusions Both sequential therapy with GnRH-a combined with DNG and DNG monotherapy are effective in relieving dysmenorrhoea,reducing CA125 levels,and increasing hemoglobin levels in patients with adenomyosis.However,sequential therapy is associated with a lower incidence of irregular vaginal bleeding compared to monotherapy and demonstrates a potential advantage in controlling uterine volume growth.

Objective:To compare the efficacy of dienogest (DNG) and levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of intrinsic and extrinsic subtypes of adenomyosis.Methods:Totally 232 patients were enrolled in the study who were diagnosed as adenomyosis by ultrasound or pelvic magnetic resonance imaging (MRI), and were classified into intrinsic and extrinsic subtypes according to different locations of lesions in MRI, treated with DNG (DNG group) or LNG-IUS (LNG-IUS group) in Peking University Third Hospital from July 2019 to December 2023. Clinical data of patients were retrospectively collected to analyze the clinical and imaging characteristics of different MRI subtypes of adenomyosis and whether there were differences in the therapeutic effects of DNG and LNG-IUS.Results:(1) Among the 232 patients enrolled, 129 were intrinsic subtype and 103 were extrinsic subtype. Among the 129 patients treated with DNG, the numbers of intrinsic and extrinsic subtype were 69 and 60, respectively. And among the 103 patients treated with LNG-IUS, the numbers of intrinsic and extrinsic subtype were 60 and 43, respectively. The mean age in DNG group [(37.5±5.6) years] was lower than that in LNG-IUS group [(40.3±4.3) years, P<0.001]. There were no significant differences in other clinical features (all P>0.05). (2) The visual analog scale (VAS) scores of dysmenorrhea and cancer antigen 125 (CA 125) levels in DNG group and LNG-IUS group were significantly decreased after treatment (all P<0.001), and hemoglobin levels were increased (both P<0.01). Compared between the two groups, the VAS score after treatment was lower in DNG group ( P<0.001), and the hemoglobin level was increased more significantly in DNG group ( P=0.016). The complete remission rates of dysmenorrhea in DNG group and LNG-IUS group were 73.0% (89/122) and 29.5% (28/95), respectively ( P=0.039). The incidence of irregular bleeding in DNG group was higher than LNG-IUS group, but there was no statistical significance [62.8% (81/129) vs 52.4% (54/103), P=0.112]. (3) Among patients with intrinsic adenomyosis, the incidence of menorrhagia was significantly higher than in those with extrinsic adenomyosis ( P<0.001), while the incidence and severity of dysmenorrhea were lower compared to extrinsic adenomyosis ( P=0.004, P=0.007, respectively). After treatment with DNG and LNG-IUS, there were no statistically significant differences in VAS scores between patients with intrinsic and extrinsic adenomyosis (all P>0.05). The incidence of irregular bleeding after DNG treatment was 78.3% (54/69) in intrinsic adenomyosis, which was higher than the 45.0% (27/60) observed in extrinsic adenomyosis ( P<0.01). Similarly, the incidence of irregular bleeding after LNG-IUS treatment was 63.3% (38/60) in intrinsic adenomyosis, higher than the 37.2% (16/43) in extrinsic adenomyosis ( P=0.009). (4) DNG treatment ( OR=19.163, 95% CI: 7.564-48.544; P<0.01) and duration of treatment ( OR=1.043, 95% CI: 1.012-1.075; P=0.007) were independent positive factors for complete remission of dysmenorrhea, while VAS score before treatment ( OR=0.654, 95% CI: 0.454-0.942; P=0.023) was negative factor. Intrinsic subtype was an independent risk factor for irregular bleeding ( OR=0.436, 95% CI: 0.235-0.811; P=0.009). Conclusions:DNG demonstrates greater advantages over LNG-IUS in terms of complete relief of dysmenorrhea and the degree of symptom alleviation. The incidence of irregular vaginal bleeding in patients with intrinsic adenomyosis is higher than in those with extrinsic adenomyosis. For patients with extrinsic adenomyosis, particularly those with prominent dysmenorrhea symptoms, DNG treatment offers greater benefits. However, for patients with intrinsic adenomyosis and those with significant menstrual disorders, a more cautious approach is required when selecting progestin therapy, along with enhanced monitoring and management.

Objective:To analyze the differences in the clinical characteristics of patients with adenomyosis of different magnetic resonance imaging (MRI) types and the differences in treatment effects after the application of dienogest.Methods:A total of 176 patients with adenomyosis who were admitted to Peking University Third Hospital from June 2017 to February 2023 were included in the study, and all of them were clearly classified by pelvic MRI and treated with dienogest. The clinical characteristics and treatment of the patients were retrospectively collected, and the patients were divided into endogenous type, exogenous type and penetrating type by MRI. The differences in clinical symptoms, imaging features and treatment effect of patients with adenomyosis of different MRI types were analyzed.Results:(1) The percentages of patients with endogenous, exogenous, and penetrating types were 40.9% (72/176), 35.2% (62/176) and 23.9% (42/176), respectively. The proportion of dysmenorrhea in patients with endogenous type (90.3%, 65/72) was significantly lower than those of exogenous type (100.0%, 62/62) and penetrating type (97.6%, 41/42; χ2=7.853, P=0.020), while there was no significant difference between exogenous type and penetrating type ( P>0.05). There were no statistically significant differences in menarche time, menstrual cycle and menstrual period among the three types of patients (all P>0.05), there was also no statistically significant difference in the proportion of menstrual abnormalities (including heavy and irregular menstrual bleeding; P>0.05). The proportions of ovarian endometrioma and deep infiltrating endometriosis in exogenous and penetrating types were significantly higher than that in endogenous type (all P<0.05). (2) The pain scores of all patients were significantly lower than those before treatment (all P<0.001), the proportion of patients with exogenous type (62.9%, 39/62) who had complete remission after treatment was higher than those of endogenous type (49.2%, 32/65) and penetrating type (46.3%, 19/41), but there was no significant difference in pain relief (i.e. the variation in the pain scores) between the three types ( P>0.05). (3) Endogenous type ( OR=0.361, 95% CI: 0.147-0.883; P=0.026), failure to apply gonadotropin-releasing hormone agonist (GnRH-a) in advance ( OR=0.208, 95% CI: 0.083-0.518; P<0.001), cystic changes ( OR=2.671, 95% CI: 1.108-6.437; P=0.029) and abnormal menstruation ( OR=3.466, 95% CI: 1.464-8.209; P=0.005) were independent risk factors for irregular bleeding after dienogest treatment. Conclusions:(1) There are obvious differences in the clinical characteristics of patients with adenomyosis of different MRI types, and patients with exogenous and penetrating types are more likely to have dysmenorrhea symptoms. (2) Dienogest could significantly alleviate the symptoms of dysmenorrhea in patients with adenomyosis. (3) Endogenous type, failure to take GnRH-a in advance and associated menstrual abnormalities are independent risk factors for irregular bleeding after dienogest treatment.

Objective To compare the therapeutic efficacy of sequential therapy with gonadotropin releasing hormone agonist(GnRH-a)combined with dienogest(DNG)versus DNG alone in patients with adenomyosis.Methods A retrospective analysis was conducted on clinical data from 129 patients diagnosed with adenomyosis by ultrasound and MRI between August 2020 and December 2023.Among them,60 patients received sequential therapy with GnRH-a followed by DNG(combination group)and 69 patients received DNG monotherapy(monotherapy group).There were no significant differences in baseline characteristics,including age,incidence of dysmenorrhea,incidence of menorrhagia,uterine volume,and type of adenomyosis between the two groups(P>0.05).The combination group received subcutaneous injections of leuprorelin3.75 mg every28 d for3 to 6 cycles,followed by oral DNG 2 mg/d for more than 3 months.The monotherapy group received oral DNG 2 mg/d alone for more than 3 months.Treatment outcomes and adverse reactions were compared between the two groups.Results The median duration of DNG treatment was 16.0(10.2,26.0)months in the combination group and13.0(6.0,23.0)months in the monotherapy group.The difference between the two groups was not statistically significant(Z=-1.587,P=0.113).Both groups showed a significant reduction in dysmenorrhea as measured by the Visual Analogue Scale(VAS)score,a significant decrease in serum CA125 levels,and a significant increase in hemoglobin levels after treatment compared to before treatment(all P<0.001).There were no significant differences between the two groups(P>0.05).Regarding uterine volume,the combination group showed a trend toward reduction after treatment[146.3(77.6,250.4)cm3 vs.118.4(82.4,233.4)cm3,Z=0.272,P=0.785],while the monotherapy group showed a significant increase in uterine volume compared to before treatment[162.9(110.8,256.0)cm3 vs.187.6(123.7,276.2)cm3,Z=2.945,P=0.003].The incidence of irregular vaginal bleeding in the combination group[50.0%(30/60)]was lower than that in the monotherapy group[75.4%(52/69),χ2=8.914,P=0.003].Conclusions Both sequential therapy with GnRH-a combined with DNG and DNG monotherapy are effective in relieving dysmenorrhoea,reducing CA125 levels,and increasing hemoglobin levels in patients with adenomyosis.However,sequential therapy is associated with a lower incidence of irregular vaginal bleeding compared to monotherapy and demonstrates a potential advantage in controlling uterine volume growth.

Objective To investigate the effects of platelet-rich plasma-derived exosomes(PRP-Exos)on the proliferation and migration of tendon stem/progenitor cell(TSPC).Methods PRP-Exos were extracted through the combination of polymer-based precipitation and ultracentrifugation.The morphology,concentration,and particle size of PRP-Exos were identified by transmission electron microscopy and nanoparticle tracking analysis.The expression levels of surface marker proteins on PRP-Exos and platelet membrane glycoproteins were deter-mined by Western blot analysis.Rat TSPC was extracted and cultured,and the expression of surface marker mol-ecules on TSPC was detected using flow cytometry and immunofluorescence staining.The proliferation of TSPC in-fluenced by PRP-Exos was evaluated using CCK-8 assay and EdU assay.The effect of PRP-Exos on the migration of TSPC was evaluated by cell scratch assay and Transwell assay.Results The extracted PRP-Exos exhibit typi-cal saucer-like structures,with a concentration of 4.9 ×1011 particles/mL,an average particle size of(132.2±56.8)nm,and surface expression of CD9,CD63 and CD41.The extracted TSPC expressed the CD44 pro-tein.PRP-Exos can be taken up by TSPC,and after co-cultured for 48 h,concentrations of 50 and 100 μg/mL of PRP-Exos significantly promoted the proliferation of TSPC(both P＜0.001),with no statistical difference be-tween the two concentrations(P=0.283).Additionally,after co-cultured for 24 h,50 μg/mL of PRP-Exos significantly promoted the migration of TSPC(P＜0.001).Conclusion Under in vitro culture conditions,PRP-Exos significantly promote the proliferation and migration of rat TSPC.

Purpose To predict the 2015 American thyroid association(ATA)recurrence risk stratification based on ultrasonographic features and Hashimoto's thyroiditis(HT)-specific antibody status of papillary thyroid carcinoma(PTC)in the context of HT.Materials and Methods A retrospective analysis was conducted on the ultrasonographic and clinical data of 479 patients with coexisting PTC and HT,who underwent their first thyroid surgery at the First Medical Center of Chinese PLA General Hospital from January 2017 to December 2019.All patients were divided in chronological order into a training group(n=327)and a validation group(n=152).Multivariate Logistic regression analysis was utilized to identify independent factors associated with high recurrence risk stratification according to the ATA guidelines.Predictive models were constructed and screened,and the efficacy of these models was evaluated using the area under the curve,calibration curves and Brier scores.Results Multivariate Logistic regression analysis identified the following as independent predictive factors for high recurrence risk stratification:multifocal malignancy of nodules(OR=3.812,95％CI 1.275-11.397,P=0.017),nodule contact with the capsule(OR=8.012,95％CI 1.647-38.972,P=0.010),microcalcifications(OR=4.220,95％CI 1.302-13.678,P=0.016),an aspect ratio＞1(OR=4.017,95％CI 1.286-12.548,P=0.017),abundant nodule vascularity(OR=6.120,95％CI 2.225-16.832,P＜0.001),maximum nodule diameter ≥1 cm(OR=4.784,95％CI 1.360-16.833,P=0.015),a glandular echo characteristic of typical HT(OR=0.114,95％CI 0.039-0.330,P＜0.001),and anti-thyroid peroxidase antibody monopositivity(OR=0.088,95％CI 0.006-1.299,P=0.077).The predictive model demonstrated strong performance,as evidenced by the area under the curve of 0.942(95％CI 0.911-0.972)in the training set and 0.933(95％CI 0.878-0.990)in the validation set.Both groups exhibited well-fitting calibration curves.The Brier scores were 0.054 and 0.058 for the training and validation sets,respectively,indicating excellent predictive efficacy of the model.Conclusion The preoperative prediction model,based on ultrasonographic features combined with antibody status,demonstrates good efficacy in assessing ATA recurrence risk stratification for coexisting PTC and HT patients,which can assist clinicians in formulating treatment plans.

Objective To investigate the expression of NLRP3 in different time point of HIBD neonatal rats and to search for critical time points and alleviate HIBD dysfunction.Methods 96 newborn rats of 7 days old were randomly divided into HIBD group(n=48) and Sham operation group(n=48).HIBD model was prepared by referring to Rice method.Brain tissue was taken after 6 h,24 h,72 h,7 d.Brain injury was detected by HE stain.The expression and distribution of NLRP3 and Caspase-1 were detected by immune fluorescence and Western blot,and IL-1β and IL-18 were detected by ELISA.Results HE staining and immunofluorescence showed that NLRP3 protein (HIBD group (0.63±0.07),Sham group(0.43±0.04)) was increased significantly since 6 h in HIBD group,and its downstream protein Caspase-1,IL-1β and IL-18 were successive activated.The results showed IL-1β (HIBD group(732.28± 108.42)pg/ml,Sham group(584.58± 36.35) pg/ml) was increased significantly since 6 h in HIBD group;Caspase-1 (HIBD group(0.67±0.09),Sham group(0.30±0.05)),IL-18 (HIBD group(683.84±31.83) pg/ml,Sham group(571.32±50.91) pg/ml) was increased significantly since 24 h in HIBD group(P＜0.05).Conclusion NLRP3 and its downstream inflammatory cytokines IL-1 β and IL-18 are up-regulated when HIBD occurs.The change of NLRP3protein expression in group HIBD is earlier than changes of neuron.NLRP3 signal may mediate and participate in the occurrence and development of HIBD.

Objective To improve the classroom environment and students' learning effect and in-novation of classroom teaching mode. Method We took stomatology students of Grade 2012 (control group, 60 people) and Grade 2013 (experimental group, 69 people) as research subjects, and in the control group, the traditional teaching method was used, while the experimental group was based on the mixed mode of the flipped classroom. By comparison of the result of questionnaire survey and final examination between the experimental group and control group, we made clear the difference between blended classroom teaching and traditional classroom teaching. SPSS 16.0 was used for statistical analysis and the data was made t test and rank sum test, and the result was showed by rate and (x±s). Result The classroom performance of the control group was (14.78±4.27), and the experimental result was (14.49±4.49), in the experimental group, the internal and external performance of the experimental group was (22.19±7.21), the experimental result was (7.12±1.33). By comparison of the result of examination between the experimental group (49.01±7.28) and control group (46.32 ±7.44), medical immunology test scores were significantly different (P<0.05), and the experimental group was better than the control group. It showed that the mixed teaching model had more advantages in improving the academic performance. The results of questionnaire survey showed that flipped classroom teaching was better than traditional classroom teaching in ability training which included self learning ability (68.18%, 45 people), analysis and problem solving skills (68.18%, 45 people), team work and communication skills (56.06%, 37 people), ability of retain knowledge (46.97%, 31 people), however students who liked and accepted this new teaching model only accounted for about 30.00%. Conclusion Inte-gration of flipped classroom mode with traditional mode will enhance the students' learning efficiency and achievements, as well as promote students' ability.