Objective To investigate the effects of different contrast injection schemes on the image quality of triple-rule-out com-puted tomography angiography(TRO-CTA).Methods A total of 691 patients with acute chest pain who underwent TRO-CTA exami-nation from multiple centers were prospectively selected and randomly divided into mixed group and unmixed group according to dif-ferent contrast injection methods.The image quality of aorta,pulmonary artery and coronary artery in the two groups was evaluated subjectively and objectively and the radiation dose was calculated.Results There were no significant differences in subjective image quality scores,aorta and coronary CT values,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)between the two groups(P>0.05),while there were significant differences in pulmo-nary CT values,SNR,CNR and radiation dose between the two groups(P<0.05).Conclusion The utilization of a mixed contrast injection scheme in TRO-CTA can satisfy diagnostic require-ments while ensuring a low proportional dosage and reduced radiation dose,which has clinical application value.

Objective To evaluate the predictive value of a nomogram model developed by integrating clinical and ultrasound multiparameters for HER-2-positive breast cancer.Methods This study retrospectively enrolled 343 patients with pathologically confirmed breast cancer from three medical centers and randomly divided them into training and validation cohorts.Univariate analysis,LASSO regression,and multivariate logistic regres-sion were conducted on the training set to identify independent prognostic factors and construct a nomogram model.Bootstrap resampling with 1000 iterations was performed to evaluate the model's robustness.Model calibration was assessed using calibration curves and the Hosmer-Lemeshow goodness-of-fit test.Receiver operating characteristic(ROC)curves were generated to evaluate model discrimination,and the area under the curve(AUC)along with other performance metrics were calculated.Decision curve analysis was employed to assess the clinical utility of the model,and the validation cohort was used for external validation.Results Univariate,LASSO,and multivariate regression analyses demonstrated that age,TTP(time to peak),and the presence of a filling defect sign were independent predictors of HER-2-positive breast cancer(all P<0.05).Based on these independent predictors,a nomogram model was constructed.Bootstrap validation with 1,000 resamples indicated that the model's predictive performance was stable.The Hosmer-Lemeshow test confirmed satisfactory model calibration,while the calibration curve illustrated accurate prediction probabilities.The area under the curve(AUC)for the training set was 0.863(95%CI:0.806～0.920),and for the validation set,it was 0.846(95%CI:0.764～0.929),indicating strong discriminative and generalization capabilities.Additionally,the clinical decision curve analysis demonstrated favor-able clinical utility.Conclusion A nomogram model integrating clinical and multimodal ultrasound parameters demonstrates potential utility in predicting HER-2-positive breast cancer.

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 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.

Cancer immunotherapy is currently a very promising therapeutic strategy for treating tumors. However, its effectiveness is restricted by insufficient antigenicity and an immunosuppressive tumor microenvironment (ITME). Pyroptosis, a unique form of programmed cell death (PCD), causes cells to swell and rupture, releasing pro-inflammatory factors that can enhance immunogenicity and remodel the ITME. Nanomaterials, with their distinct advantages and different techniques, are increasingly popular, and nanomaterial-based delivery systems demonstrate significant potential to potentiate, enable, and augment pyroptosis. This review summarizes and discusses the emerging field of nanomaterials-induced pyroptosis, focusing on the mechanisms of nanomaterials-induced pyroptosis pathways and strategies to activate or enhance specific pyroptosis. Additionally, we provide perspectives on the development of this field, aiming to accelerate its further clinical transition.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

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.