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.

Objective:To explore the diagnostic value of the macrophage activation syndrome/systemic juvenile idiopathic arthritis（MS）score in macrophage activation syndrome（MAS）associated with systemic juvenile idiopathic arthritis（sJIA），and to provide a reference for clinical work.Methods:This study was a retrospective case-control analysis，conducted on the patients initially diagnosed as sJIA-associated with MAS and admitted into the Department of Rheumatology and Immunology of Children's Hospital Affiliated to Xi 'an Jiaotong University from July 1st，2016 to June 30th，2023. All of the patients met the diagnostic criteria for patients with MAS associated with sJIA according to the 2016 European Alliance of Associations for Rheumatology（EULAR）/American College of Rheumatology（ACR）/Pediatric Rheumatology International Trials Organization（PRINTO）standards. The basic information at baseline，clinical manifestations，and auxiliary examination results were collected. The MS score was applied to re-evaluate the children diagnosed as sJIA-associated with MAS. When the MS score ≥-2.1，the possibility of sJIA with MAS was high. Thirty cases of sJIA without MAS were randomly selected as the control group.Results:There were 28 cases in the MAS group，including 13 males（46.43%）and 15 females（53.57%），with an average age of（7.51±4.01）years. Compared with the control group，the MAS group were significantly more likely to have high fever（ χ2=8.539， P=0.003），hepatomegaly（ χ2=11.621， P<0.001），splenomegaly（ χ2=11.710， P<0.001）and neurological involvement（ χ2=27.619， P<0.001），with the differences being statistically significant. Meanwhile，there were statistically significant differences between the two groups in terms of white blood cell count（ Z=-4.001， P<0.001），neutrophil count（ Z=-3.659， P<0.001），platelet count（ Z=-4.687， P<0.001），albumin level（ Z=-4.018， P<0.001），alanine aminotransferase（ Z=-3.846， P<0.001），aspartate aminotransferase（ Z=-5.932， P<0.001），lactate dehydrogenase（ Z=-6.150， P<0.001），triglycerides（ Z=-5.874， P<0.001），fibrinogen（ Z=-5.808， P<0.001），ferritin（ Z=-5.280， P<0.001），erythrocyte sedimentation rate（ Z=-3.971， P<0.001），ferritin/erythrocyte sedimentation rate（ Z=-5.433， P<0.001），reduction of two-line cells in blood（ χ2=11.408， P<0.001）and the presence of hemophagocytosis in bone marrow smears（ χ2=28.260， P<0.001）. Moreover，there was a statistically significant difference in MS scores between the two groups（ Z=-6.148， P<0.001），with higher MS scores in the MAS group. Nevertheless，this study showed the median MS scores of both groups ≥-2.1. Conclusion:The MS score was significant to a certain degree as reference for the diagnosis of MAS，and this study showed that the MS score in the MAS group was significantly higher than the control group. However，the median MS scores in both groups were no less than -2.1. This might be related to the influence of factors during the assessment，which made it necessary to optimize the cutoff values of the MS score. Therefore，prospective studies should be carried out on the role of MS score in early identification of MAS.

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.

OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but there are still many patients who suffer tumor recurrence. However, valuable predictors of treatment outcomes remain limited. This study aimed to assess the value of the serum immune biomarkers to predict the prognosis. METHODS: We reviewed cervical cancer patients treated with CCRT between January 2014 and May 2018 at Peking Union Medical College Hospital. The systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and lactate dehydrogenase (LDH) were calculated using blood samples. The relationship between immune markers and the treatment outcome was analyzed. The area under the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency. The Cox proportional hazards model and log-rank were used to predict overall survival (OS) and disease-free survival (DFS). RESULTS: This study included 667 patients. Among them, 195 (29.2%) patients were defined as treatment failure, including 127 (19.0%) patients with pelvic failure, 94 (14.1%) distant failure, and 25 (3.7%) concurrent pelvic and distant failure. It revealed that the tumor stage, size, metastatic lymph nodes (MLNs), and serum immune biomarkers, such as SII, SIRI, and LDH, were significantly related to treatment outcomes. We demonstrated that the optimal cut-off of the SII, SIRI, and LDH were 970.4 × 10 9 /L, 1.3 × 10 9 /L, and 207.52 U/L, respectively. Importantly, this study presented that LDH level had the highest OR (OR = 4.2; 95% CI [2.3-10.8]). Furthermore, the OS and DFS for patients with pre-SII ≥970.5 × 10 9 /L were significantly worse than those with pre-SII <970.5 × 10 9 /L. Similarly, pre-SIRI ≥1.25 × 10 9 /L and pre-LDH ≥207.5 U/L were related to poor survival outcomes. CONCLUSIONS This study demonstrated that the baseline SII, SIRI, and LDH levels can be used to accurately and effectively predict the treatment outcomes after CCRT and long-term prognosis. Our results may offer additional prognostic information in clinical, which helps to detect the potential recurrent metastasis in time.
Humans ; Female ; Uterine Cervical Neoplasms/drug therapy* ; Middle Aged ; Adult ; Aged ; Chemoradiotherapy/methods* ; L-Lactate Dehydrogenase/blood* ; Treatment Outcome ; Disease-Free Survival ; Prognosis ; ROC Curve ; Biomarkers, Tumor/blood* ; Proportional Hazards Models

Objective:To summarize the clinical data of single-center juvenile dermatomyositis（JDM）complicated with interstitial lung disease（ILD），and provide experience for pediatricians.Methods:Data of 61 children with JDM who were admitted to Children's Hospital affiliated to Xi'an Jiaotong University from January 2016 to May 2023 were collected. General data，clinical symptoms，chest high-resolution CT，laboratory examination and myositis antibody spectrum of the children were recorded.Results:Among the 61 children with JDM，there were 30 cases（13 males and 17 females）without ILD. The age of onset was 5.96（3.50，8.92）years and the course of disease was（11.79±20.00）months. There were 31 cases with ILD（14 males and 17 females），the age of onset was 7.42（4.50，10.08）years，and the duration of ILD was（5.47±8.09）months. There was statistical difference in the course of disease between the two groups（ P<0.05），but no statistical difference in gender and age between the two groups（ P>0.05）. Among 61 children with JDM，there were statistical differences in fever between the two groups（ P<0.05），but no statistical differences in heliotrope discoloration，gottron’s papules，calcinosis and myasthenia between the two groups（ P>0.05）. AST and FER showed statistical difference between the two groups（ P<0.05），while CK，LDH，CK-MB，ESR，C3 and C4 showed no statistical difference（ P>0.05）. All 61 cases of children were tested for myositis antibody spectrum，and there was statistical difference in anti-MDA5 antibody between the two groups（ P<0.05），but no statistical difference in the rest（ P>0.05）. There were statistical differences between the two groups in the treatment of methotrexate，hydroxychloroquine and cyclophosphamide（ P<0.05）. A total of 11 cases（36.67%）in the without ILD group were treated with biologics（8 adalimumab，2 infliximab and 1 tofacitinib），and 23 cases（74.19%）in the ILD group were treated with biologics（11 adalimumab，9 tofaciib，2 infliximab and 1 tocilizumab）. All 61 cases with JDM were followed up. Among the 30 children without ILD，1 case was lost to follow-up 2 months after treatment，and the rest were treated effectively without death. Among the 31 children with ILD，3 cases died of severe pulmonary infection with multidrug-resistant bacteria during treatment，of which 1 case was positive for anti-MDA5 antibody and 2 cases were negative for myositis specific antibody. Conclusion:JDM is more likely to be complicated with ILD，fever is more likely to occur in ILD group，and children with positive anti-MDA5 antibody are more likely to occur ILD. Biologic agents such as adalimumab and tofacitinib are effective in combination therapy. In the course of treatment，multi-drug resistant bacteria infection should be guarded against to reduce mortality.

ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.