The ambiguity of symptom information in traditional Chinese medicine （TCM） syndrome differentiation can be amplified in the direct reasoning process from symptoms to syndromes in the absence of constraints， which affects the accuracy and stability of intelligent syndrome differentiation. TCM disease concepts， while historically rational， are structurally ambiguous in both their connotation and extension， making it difficult to serve as stable prior knowledge in intelligent modeling. In contrast， modern medical diseases， based on objective testing and quantifiable indicators， have relatively clear boundaries and reproducible standards. This study proposes a disease-syndrome combination model， adopting modern medical diseases as structural prior variables to reconstruct the hierarchical relationships among disease， symptoms， and syndromes. By applying disease constraints， effective screening of information from the four examinations and compressing the reasoning space are achieved. Furthermore， by integrating artificial intelligence technologies， such as multimodal fusion and knowledge graphs， an intelligent syndrome differentiation model driven by both prior knowledge and clinical data is constructed， providing a feasible path to enhance the accuracy of syndrome differentiation and realize the intelligentization of TCM diagnosis and treatment.

To explore the clinical value of a multimodal predictive model based on multiparametric magnetic resonance imaging(MRI) radiomics combined with deep learning(DL) features for the preoperative noninvasive assessment of mismatch repair-deficient(MMRd) status in endometrial cancer(EC).

Objective To characterize Schistosoma japonicum Class F G protein-coupled receptors (GPCRs), and to decipher the biological function of S. japonicum Smoothened receptor (SjSMO), so as to provide insights into screening of novel anti-schistosomal drug targets. Methods Six Class F GPCRs were identified from the S. japonicum GPCR library using a hidden Markov model (HMM) and genome annotation filese, including five frizzled (FZD) receptors (SjFZD4, SjFZD5, SjFZD7, SjFZD8, SjFZD10) and one Smoothened receptor (SjSMO). Protein domain analysis was performed at the SMART website, and a phylogenetic tree was built with the software MEGA 11.0 and refined with the Interactive Tree Of Life (iTOL) tool. The expression profile and tissue localization of S. japonicum class F GPCRs were analyzed using the real-time fluorescence-based quantitative PCR (RT-qPCR) assay and in situ hybridization, and the effects of SjSMO on parasite growth, development, reproduction, and oviposition were examined using in vivo and in vitro RNA interference (RNAi). S. japonicum adult worms were selected for double-stranded RNAi (dsRNA) in in vitro experiments, and a green fluorescent protein (GFP) negative control group and SjFZD4, SjFZD5, SjFZD7, SjFZD8, SjFZD10, and SjSMO dsRNAi groups were assigned to observe the parasite vitality and state and calculate the female and male rating rate. For in-vivo animal experiments, 6-week-old SPF female mice of the Kunming strain were randomly divided into a GFP dsRNA negative control group and SjFZD4, SjFZD5, SjFZD7, SjFZD8, SjFZD10, and SjSMO dsRNAi groups. Worms and liver tissues were collected for measurement of the worm length and estimation of the worm burdens, and changes in the parasite reproductive organs were observed using alum carmine staining. In addition, the number of S. japonicum eggs in mouse livers was counted and the pathological damages of mouse livers were recorded. Results The five FZD receptors and one Smoothened receptor all contained a conserved Frizzled domain. Phylogenetic analysis revealed that SjSMO formed an independent evolutionary clade, which exhibited a far genetic distance from the FZD family. RT-qPCR assay quantified stable SjSMO expression in male worms but gradually decreased in female worms with worm development, and in situ hybridization revealed high systemic expression of SjSMO. In vitro RNAi results revealed a significant difference in pairing rates among all groups (χ² = 130.530, P < 0.000 1). Only the SjSMO interference group exhibited a markedly reduced worm pairing rate of 20.00%, which was significantly lower than that of the control group (94.74%) (P < 0.000 1), accompanied by decreased worm vitality. In contrast, no statistically significant differences in pairing rates were observed between each FZD family gene interference group and the control group (all P > 0.05). In vivo RNAi assay revealed that SjSMO dsRNAi 1 to 26 days post-infection resulted in a significant reduction in worm length, with reductions in the male worm length by 32.27% and female worm length by 36.77% as compared to controls [male worms: (6.51 ± 1.77) mm vs. (9.62 ± 1.44) mm, t = 7.196, P < 0.000 1; female worms: (5.49 ± 1.36) mm vs. (8.68 ± 2.60) mm, t = 5.953, P < 0.000 1], as well as arrest of testicular development in male worms and ovarian development in females. In addition, SjSMO dsRNAi 26 to 42 days post-infection was found to significantly reduce hepatic egg burdens in mice, with a 49.10% reduction in the count of liver eggs in the SjSMO dsRNAi group relative to the GFP dsRNA negative control group [(2 824 ± 844) eggs per gram vs. (5 548 ± 797) eggs per gram; t = 4.064, P < 0.05], and to alleviate granuloma formation and severity of hepatic fibrosis. Conclusion SjSMO is a key receptor that regulates the growth, development, reproduction, and oviposition of S. japonicum, which provides a new potential target for development of anti-schistosomal drugs.

Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

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 explore the potential risk factors of recurrence in patients with systemic juvenile idiopathic arthritis (sJIA).Methods:We enrolled patients with sJIA admitted to the Department of Rheumatology and Immunology, Xi′an Children′s Hospital affiliated to Xi′an Jiaotong University from January 2018 to June 2024. Cox proportional hazard models were used to identify clinical features associated with risk of recurrence.Results:This study included a total of 108 children with sJIA, with a median onset age of 79.5 (53.0, 121.5) months. Among them, 52 were male (48.1%) and 56 were female (51.9%). The median time from disease onset to diagnosis was 29.5 (19.0, 57.0) days, and 105 children achieved clinical remission during follow-up. Out of 108 patients with sJIA, 105 patients who achieved clinical remission were enrolled with a median follow-up of 38.0 months. Among them, 28 (26.7%) patients had at least once recurrence. According to the multivariate analysis, macrophage activation syndrome [HR(95% CI)=2.375(1.096, 5.149), P=0.028] and alkaline phosphatase [HR(95% CI)=1.006(1.001, 1.010), P=0.017] were associated with increased risk of recurrence. Conclusion:Our study indicated that recurrence could appear in at least 26.7% patients with sJIA. The high alkaline phosphatase and MAS at initial attack may be independent risk factors of recurrence in patients with systemic Juvenile Idiopathic Arthritis.

Developmental dysplasia of hip(DDH)usually occurs in children,and delayed diagnosis of DDH might lead to serious complications and influence long-term prognosis.The application of artificial intelligence(AI)in medical images helps to quantitatively individualize image data,reduce bias generated by manual analysis and achieve early and accurate diagnosis of children DDH.The research progresses of AI in imaging diagnosis of children DDH were reviewed in this article.

Objective To investigate the value of morphological and hemodynamic parameters of CT angiography(CTA)for predicting recurrence of intracranial aneurysms(IA)after endovascular embolization.Methods Totally 205 patients with ruptured IA who underwent endovascular embolization were retrospectively collected and divided into recurrence group(n=35)and non-recurrence group(n=170)according to follow-up results after embolization.The morphological and hemodynamic parameters of IA in CTA before treatment were compared between groups.Variance inflation factor(VIF)was used to explore whether there was collinearity between morphological and hemodynamic parameters,and those without collinearity were included in univariate and multivariate logistic regression analysis to screen predictors of recurrence of IA after endovascular embolization.Two prediction models were constructed based on morphological parameters(model 1)and combination with hemodynamic parameters(model 2).Receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate the predictive efficacy of models.Results The maximum diameter,aneurysm neck width,maximum height,maximum vertical height and size ratio(SR)of IA in recurrence group were all higher than those in non-recurrence group(all P＜0.05),while gradient oscillatory number(GON)in recurrence group was lower than that in non-recurrence group(P＜0.05).The neck width,SR,pressure at IA neck plane,intra-aneurysm time-averaged wall shear stress(TAWSS),oscillatory shear index(OSI)and GON had no significant collinearity(all VIF＜10),among which the neck width,SR and TAWSS were all independent predictors(all P＜0.05).AUC of model 1 and model 2 for predicting recurrence of IA after endovascular embolization was 0.668 and 0.723,respectively,which of model 2 was higher than which of model 1(integrated discrimination improvement index was 0.055,P=0.025).Conclusion CTA morphological parameters combined with hemodynamic parameters of IA could be used to predict its recurrence after endovascular embolization.