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 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 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 investigate the toxicity attenuation and efficacy potentiation effects of Shiquan Dabu Tang (SDT) on high dose chemotherapy in T739 mice with bladder carcinoma. Methods Mouse bladder carcinoma tissue was inoculated subcutaneously into T739 mice to establish tumor-beating mice model. The tumor-bearing mice were randomly divided into a CTX group (100, 200, 400 mg/Kg respectively), a SDT group (high or low dose respectively), a high-dose SDT combined with 200 mg/Kg CTX group and a control group. The body weight, diameter of tumor nodules and complete blood count were observed subsequently. Results Different doses of SDT could effectively inhibit tumor growth in mice. SDT + CTX treatment significantly prolonged the survival time of mice by 49.4±23.3 days (P<0.01, 0.05, 0.01), compared with high dose SDT treatment (17.4±5.77) days, 200 mg/kg CTX treatment (23±14.02) days and control group (11.75±2.06) days respectively. The peripheral platelet count increased more significantly in mice treated with SDT within a week as compared to mice without SDT treatment (P<0.05). The peripheral RBC count and liB concentration increased more significantly in mice treated with SDT for 2 weeks as compared to mice without SDT treatment (P<0.05). Conclusions SDT could enhance the anti-tumor effects of high dose CTX on tumor-bearing mice and reduce toxicity in its peripheral red blood cells. The results showed that SDT combined with high dose of CTX chemotherapy had toxicity attenuation and efficacy potentiation effects in tumor-beating T739 mice.

AIM: To investigate the significance and function of IFN-γ on the changes of peripheral blood platelet count during tumor-rejection induced by a low dose of melphalan in C57BL/6 mice. METHODS: Mouse tumor rejection model induced by a single dose of melphalan was used in this experiment. Different gene-type tumor-bearing mice (IFN-γ~(+/-) and IFN-γ~(-/-)), which had the same genetic background of C57BL/6, were treated intraperitoneally with melphalan (7.5 mg/kg). Tumor size was observed and recorded every one to three days in these different gene-type mice subsequently. Blood samples were obtained from orbital venous sinus on different days before and after melphalan treatment, and then complete blood counts were performed. The function of IFN-γ on the efficacy of chemotherapy and the changes of blood platelet count in IFN-γ~(+/-) and IFN-γ~(-/-) mice after melphalan treatment was analyzed. RESULTS: There was no significant difference in tumor sizes and blood platelet count between IFN-γ~(-/-) and IFN-γ~(+/-) mice (P>0.05). On the first day after melphalan (7.5 mg/kg) treatment, there were no significant changes in tumor sizes between mice in these two groups (P>0.05). Tumors shrank a little in IFN-γ~(-/-) mice and then grew gradually. Tumors relapsed in 2 w after melphalan injection in all IFN-γ~(-/-) mice, while tumor volumes decreased progressively and tumor cured at last in IFN-γ~(+/-) mice. The number of blood PLT in IFN-γ~(+/-) mice increased to (1935±378)×10~9/L 6 h after melphalan treatment, significantly higher than before (P<0.01); While in IFN-γ~(-/-) mice it was (1183±186)×10~9/L 6 h after melphalan treatment, no obvious increase than before. There was significant difference in blood PLT 6 h after melphalan treatment between IFN-γ~(+/-) and IFN-γ~(-/-) mice (P<0.01). Later, the numbers of blood PLT in IFN-γ~(+/-) mice decreased gradually and it dropped to normal (1158±270)×10~9/L on 11th day after melphalan treatment (P>0.05); While it sustained in normal range in IFN-γ~(-/-) mice. There was no significant difference in blood platelet count between IFN-γ~(-/-) and IFN-γ~(+/-) mice. CONCLUSION: Peripheral blood platelet count increased on the first day after melphalan treatment and tumors cured in IFN-γ~(+/-) mice; While tumors relapsed and there is no increase in blood platelet count on the first day after melphalan treatment in IFN-γ~(-/-)mice. These data indicated that the increase of blood PLT count was related to the function of IFN-γ in tumor-bearing mice in vivo during tumor rejection induced by a low dose of melphalan.

Variations in the insertion of the M. trapezius in 50 Chinese female bodieswere studied and analyzed. It was found that the presence of the anomalousinsertion of this muscle was 22?5.86% in terms of body or 12?3.25% in termsof side. The anomalous insertion consisted of separation of a part of the mus-cular fibers which are inserted at some distance from the normal attachment. Five types have been classified according to the manner of attachmentby some authors. However, the present author failed to find "Type 3" (joiningthe M. sterno-cleido-mastoideus without clavicular insertion) in his study. The probable cause of this anomaly was discussed from the point of viewof its development.