OBJECTIVES: To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism. METHODS: MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin. RESULTS: The IC₅₀ of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio. CONCLUSIONS DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Apoptosis/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/metabolism* ; Cell Line, Tumor ; Artemisinins/pharmacology* ; Female ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Survivin

Identifying drug-drug interactions (DDIs) is essential to prevent adverse effects from polypharmacy. Although deep learning has advanced DDI identification, the gap between powerful models and their lack of clinical application and evaluation has hindered clinical benefits. Here, we developed a Multi-Dimensional Feature Fusion model named MDFF, which integrates one-dimensional simplified molecular input line entry system sequence features, two-dimensional molecular graph features, and three-dimensional geometric features to enhance drug representations for predicting DDIs. MDFF was trained and validated on two DDI datasets, evaluated across three distinct scenarios, and compared with advanced DDI prediction models using accuracy, precision, recall, area under the curve, and F1 score metrics. MDFF achieved state-of-the-art performance across all metrics. Ablation experiments showed that integrating multi-dimensional drug features yielded the best results. More importantly, we obtained adverse drug reaction reports uploaded by Xiangya Hospital of Central South University from 2021 to 2023 and used MDFF to identify potential adverse DDIs. Among 12 real-world adverse drug reaction reports, the predictions of 9 reports were supported by relevant evidence. Additionally, MDFF demonstrated the ability to explain adverse DDI mechanisms, providing insights into the mechanisms behind one specific report and highlighting its potential to assist practitioners in improving medical practice.

Objective To investigate the effects of adiponectin(APN)on the proliferation,migration,and invasion of ovarian cancer cells and its potential association with the phosphatidylinositol 3-kinase(PI3K)/pro-tein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods A2780 and SK-OV3 cell lines were selected.AdipoR1 mRNA expression was detected by real-time polymerase chain reaction(RT-PCR).The CCK-8 assay was employed to evaluate APN-induced proliferation,while scratch wound heal-ing and Transwell assays were conducted to assess migration and invasion capabilities.Western blot analysis was performed to measure the expression levels of PI3K,Akt,mTOR,and their phosphorylated forms(p-Akt,p-mTOR)at different time points(0-60 min)after APN treatment and across intervention groups(APN,LY294002,APN+LY294002).Results Both A2780 and SKOV3 cells expressed AdipoR1 mRNA.Compared with the control group,APN significantly enhanced the proliferation,migration,and invasion of o-varian cancer cells(P＜0.05).Under the stimulation of APN,the expression levels of p-Akt and p-mTOR in A2780 and SKOV3 cells showed a significant upward trend.The peak expression of p-Akt and p-mTOR in A2780 cells was observed at 30 minutes,while in SKOV3 cells,it occurred at 60 minutes.The expression lev-els of p-Akt and p-mTOR were significantly reduced in the LY294002 group and APN+LY294002 group(P＜0.001).Conclusion APN enhances the proliferation,migration,and invasion behavior of ovarian cancer cells by activating the PI3K/Akt/mTOR signaling pathway,and its effect can be reversed by PI3K inhibitors,providing a theoretical basis for targeted intervention in ovarian cancer progression.

Objective: To evaluate the safety and efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in the treatment of refractory autoimmune hemolytic anemia (AIHA). Methods: A retrospective analysis was performed on the clinical data of AIHA patients who underwent therapeutic whole blood exchange combined with lymphoplasmapheresis at our hospital from March 2022 to May 2025. Efficacy was assessed by comparing changes in hemoglobin, platelet count, and bilirubin levels before and after treatment. Safety was evaluated by analyzing vital signs before and after the procedure, parameters during the exchange, and adverse reactions. Results: A total of 12 AIHA patients were enrolled, completing 19 exchange procedures. The number of procedures per patient ranged from 1 to 3. The median treatment duration was 67 (65-73) minutes, with a median exchange volume of 2 025 (1 851-2 121) mL, comprising 4.5 (4-6) units of red blood cells and 1 350 (1 200-1 400) mL of plasma. Ten patients achieved partial remission, one achieved complete remission, and one showed no response, yielding an response rate of 91% (11/12). After a single session, hemoglobin increased significantly by 17.58±9.85 g/L (P<0.01), while platelets counts decreased by 45 (17.5, 79)×10 /L (P<0.05), and both systolic and diastolic blood pressure showed a significant elevation (P<0.05). However, no statistically significant differences were observed in total bilirubin, indirect bilirubin, white blood cell count, or heart rate. During the procedures, 4 adverse reactions occurred in 3 patients: one child experienced severe heart rate fluctuation twice consecutively, and two adults developed plasma allergies. All reactions resolved spontaneously without pharmacological intervention. Conclusion: The combination of therapeutic whole blood exchange and lymphoplasmapheresis appears to be a safe and effective treatment for refractory AIHA patients.

Objective:To explore the clinical distribution characteristics and changes of common inhalant allergens and food allergens in all outpatient and inpatient children visiting Shanghai Children′s Hospital from 2020 to 2024, and to provide a basis for the diagnosis, treatment and prevention of allergic diseases in children.Methods:A retrospective cohort study was conducted to retrospectively enroll all outpatient and inpatient children who visited Shanghai Children′s Hospital and underwent serum allergen-specific IgE (sIgE) antibody testing from January 2020 to August 2024, and the characteristics and changing trends of allergens in the past 5 years were analyzed. A total of 127 310 tests were included. There were 76 776 male tests (60.31%) and 50 534 female tests (39.69%). There were 27 392 tests (21.52%) aged 0-3 years (infant group), 51 596 tests (40.53%) aged 4-6 years (preschool group), 44 574 tests (35.01%) aged 7-12 years (school-age group), and 3 748 tests (2.94%) aged 13-18 years (adolescent group). The χ2 test was used for statistical analysis. Results:The difference in total positivity rate between different years was statistically significant ( χ2=2 907.478, P<0.001). The positive rates of inhalant allergens such as house dust, Dermatophagoides pteronyssinus/ Dermatophagoides farinae, cockroach, cat dander, mugwort, Humulus scandens, mold fungi mix, and food allergens such as beef and mutton increased significantly with age (The χ2 values were 649.496, 3 414.686, 303.247, 1 277.408, 40.477, 189.952, 600.737, 203.198, and 15.301, respectively, and the P values were <0.001, <0.001, <0.001, <0.001, <0.001, <0.001,<0.001,<0.001, and 0.002, respectively). The positive rates of inhalant allergen such as Ambrosia elatior (1.59%) and food allergens such as egg white (17.36%), milk (30.48%), shrimp (8.27%), crab (8.13%), codfish (2.61%), salmon (0.66%), mytilus edulis (2.89%), lobster/scallop (5.27%), cashew nuts (5.09%), peanuts (3.54%), and soybean (1.73%) were highest at the age of 0-3 years and decreased significantly with age (The χ2 values were 10.365, 2 407.443, 139.085, 872.548, 870.245, 106.823, 47.674, 47.244, 559.422, 369.800, 384.788, 153.660, respectively, and the P values were 0.016, 0.000,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001,<0.001, respectively). Inhaled allergens mainly have a greater impact on children with respiratory-related diseases such as allergic rhinitis and asthma, while food allergens mainly have a greater impact on children with atopic dermatitis/eczema. The positive rate of sIgE of various allergens in the allergic rhinitis combined asthma group were higher than that of allergic rhinitis alone, and the sIgE positive rate of total allergens and inhaled allergens was significantly higher than that of allergic rhinitis alone ( χ2=20.851, 39.155, the P values were both<0.001). Among them, the sIgE positive rate of Ambrosia elatior and cashew nuts showed significant difference ( χ2=5.044, 8.420, P=0.025, 0.004); and the sIgE positive rate of Dermatophagoides pteronyssinus/ Dermatophagoides farinae, cat dander, grass pollens mix and mold fungi mix had extremely significant difference ( χ2=26.409, 25.990, 21.283, 16.411, the P values were all <0.001). The inhaled allergens and food allergens with the highest positive rates in the 5 years were Dermatophagoides pteronyssinus/ Dermatophagoides farinae (56.21%) and milk (47.47%), and as time went by, the positive rates gradually decreased. There is a moderate correlation between the three allergens of Ambrosia elatior, Amaranthus retroflexus, and tree pollens mix (0.55, 0.70, 0.63), and there is a moderate correlation between mango and tree pollens mix (0.50). Conclusion:Dermatophagoides pteronyssinus/ Dermatophagoides farinae, cat dander, dog dander, egg white, and milk may be important allergens for children in Shanghai City from 2020 to 2024. The positive rates vary among different genders, age groups, and disease groups, but the positive rates of Dermatophagoides pteronyssinus/ Dermatophagoides farinae, milk and cat dander allergens remain in the top three.

Genomic imprinting refers to the phenomenon of differential expression of two alleles due to their different parental origins. Genes that produce genomic imprinting are usually called imprinted genes. The genetic effect caused by the presence of imprinted genes is called parent-of-origin effect. Parent-of-origin effect and genomic imprinting play important roles in the pathophysiological mechanism and occurrence and development of cardio-metabolic diseases. In-depth exploration of the law and potential roles of imprinted genes and parent-of-origin effects will help to better understand the mechanism of cardio-metabolic diseases, and also provide important theoretical basis for the precise treatment of diseases related to imprinted genes.

Objective:To analyze the epidemiological characteristics and trends of preterm births in China using medical institution survey data, thereby providing epidemiological data support for perinatal care.Methods:Based on a nationwide sampling survey on healthcare quality data from 2017 to 2022, this study included 3 547, 4 436, 4 513, 4 535, 5 068, and 5 790 medical institutions, with 7 039 107, 8 926 441, 9 006 420, 7 051 984, 7 311 862, and 7 354 062 parturient women, respectively. The overall rates of preterm birth (live births at 28 to 36 +6 weeks of gestation/overall live births) and early preterm birth (live births at 28 to <34 weeks of gestation/overall live births) were calculated at the national level, across diverse provinces, autonomous regions, municipalities and Xinjiang Production and Construction Corps, and for various levels of medical institutions. Generalized estimating equations were used to analyze the influence of maternal characteristics and medical institution characteristics on the rates of preterm birth and early preterm birth. Results:From 2017 to 2022, both the preterm birth rate and the early preterm birth rate in China showed a continuous increase. The preterm birth rate rose from 5.13% (363 036/7 079 454) in 2017 to 6.56% (487 150/7 424 734) in 2022, and the early preterm birth rate increased from 1.32% (118 021/8 971 870) in 2018 to 1.43% (106 157/7 424 734) in 2022. These rates showed an overall increasing trend in private, secondary public specialty, and general hospitals. In tertiary public specialty hospitals, these rates fluctuated around 8.0% and 2.0% from the year 2018, respectively, while in tertiary public general hospitals, these rates peaked in 2020 at 8.63% (205 570/2 381 523) and 2.19% (52 197/2 381 523), respectively. Compared with 2017, by 2022, the preterm birth rate had increased to varying degrees in all provinces, autonomous regions, municipalities and Xinjiang Production and Construction Corps, except for Henan Province [preterm birth rate in 2017 was 6.22% (27 173/437 187); preterm birth rate in 2022 was 5.83% (37 604/645 104)]. As for the early preterm birth rate, it showed a decline in Fujian, Guangdong, Guangxi, Hainan, Henan, Jiangsu, Shanghai, Xinjiang, Yunnan, and Zhejiang, but had increased to varying degrees in all other provinces , autonomous regions, municipalities and Xinjiang Production and Construction Corps across the country. The grade and location of medical institutions both had a significant impact on the preterm birth rate and early preterm birth rate (both P<0.05). For every 1% increase in the proportions of multiparous women, women of advanced maternal age, or twin pregnancies, the preterm birth rate increased by 0.014%, 0.042%, and 0.763%, and the early preterm birth rate increased by 0.004%, 0.013%, and 0.239%, respectively (all P<0.05). Conclusion:From 2017 to 2022, the preterm birth rate and early preterm birth rate in China have continued to rise, reflecting the dual challenges of changing characteristics in the childbearing population and the uneven distribution of medical and health resources faced by maternal and child healthcare in China.

Identifying drug-drug interactions(DDIs)is essential to prevent adverse effects from polypharmacy.Although deep learning has advanced DDI identification,the gap between powerful models and their lack of clinical application and evaluation has hindered clinical benefits.Here,we developed a Multi-Dimensional Feature Fusion model named MDFF,which integrates one-dimensional simplified molec-ular input line entry system sequence features,two-dimensional molecular graph features,and three-dimensional geometric features to enhance drug representations for predicting DDIs.MDFF was trained and validated on two DDI datasets,evaluated across three distinct scenarios,and compared with advanced DDI prediction models using accuracy,precision,recall,area under the curve,and F1 score metrics.MDFF achieved state-of-the-art performance across all metrics.Ablation experiments showed that integrating multi-dimensional drug features yielded the best results.More importantly,we obtained adverse drug reaction reports uploaded by Xiangya Hospital of Central South University from 2021 to 2023 and used MDFF to identify potential adverse DDIs.Among 12 real-world adverse drug reaction reports,the predictions of 9 reports were supported by relevant evidence.Additionally,MDFF demon-strated the ability to explain adverse DDI mechanisms,providing insights into the mechanisms behind one specific report and highlighting its potential to assist practitioners in improving medical practice.

Objective:To evaluate the clinical outcomes of applying an enhanced workflow in robotic-assisted total hip revision arthroplasty.Methods:A retrospective study was conducted to analyze the 25 consecutive patients who had undergone robotic-assisted total hip revision arthroplasty in which an enhanced workflow was applied at Department of Orthopaedic Surgery, Beijing Jishuitan Hospital from September 2021 to October 2024. The cohort consisted of 8 males and 17 females with an age of (64.0±12.8) years. The left side was affected in 18 cases and the right side in 7 cases. The time from initial total hip arthroplasty to revision was (159.6±86.7) months. In all patients, no significant difference was found in the preoperative femoral cortical thickness between the healthy and the affected sides. The enhanced workflow included preoperative CT modeling and planning, intraoperative registration, prosthetic removal and reconstruction, and verification of prosthesis position. A total of 18 patients underwent total hip revision involving both the acetabular and the femoral sides; 6 patients underwent simple acetabular reconstruction with retention of the original femoral stem and replacement of the femoral head; 1 patient underwent femoral revision with retention of the acetabular cup and replacement of the acetabular liner. The operative time, intraoperative blood loss, modified Harris Hip Score (mHHS) and visual analogue scale (VAS) for hip pain at the final follow-up, and follow-up complications were recorded.Results:All patients successfully completed robotic registration during surgery, with no case of intraoperative robotic termination. For the 25 patients, the operative time was (152.2±43.8) minutes, the intraoperative blood loss 600 (400, 1,000) mL, and the follow-up time 12.0 (6.0, 31.5) months. At the final follow-up, their mHHS improved from 66.0 (26.4, 75.6) points preoperatively to 93.5 (80.3, 98.9) points, and their VAS pain score decreased from 5.0 (3.0, 7.0) points preoperatively to 0.0 (0.0, 2.0) point ( P<0.05). Follow-ups revealed no case of reoperation, prosthetic loosening, joint dislocation, periprosthetic infection, or periprosthetic fracture. Conclusion:The enhanced workflow can achieve satisfactory outcomes in robotic-assisted total hip revision for patients with adequate proximal femoral bone stock.

Objective:To investigate the association between metabolic dysfunction-associated steatotic liver disease(MASLD)and the risk of adverse pregnancy outcomes,and to analyze the impact of the type and severity of cardiometabolic risk factor(CMRF)abnormalities on this association.Methods:A retrospective cohort study was conducted among primiparous women with singleton pregnancies who had registered at Beijing Friendship Hospital from March 10,2020,to December 31,2022.A total of 2 623 women were included.Basic characteristics and delivery outcomes were documented,liver ultrasound and relevant prenatal examinations were performed,and adverse pregnancy outcomes were diagnosed.Modi-fied Poisson regression models were used to analyze the association between MASLD and adverse pregnan-cy outcomes.The relationship between the type or severity of CMRF abnormalities in MASLD and the risk of adverse pregnancy outcomes was also explored.Results:After adjusting for confounding factors including age,gestational weight gain,and education level,MASLD was associated with an increased risk of cesarean section(RR=1.531,95％CI:1.304-1.799,P＜0.001),gestational diabetes melli-tus(GDM;RR=2.409,95％CI:1.948-2.979,P＜0.001),pregnancy-associated hypertension(PAH;RR=3.062,95％CI:2.069-4.533,P＜0.001),preterm birth(RR=2.145,95％CI:1.342-3.429,P=0.001),and large for gestational age(LGA;2.224,95％CI:1.599-3.095,P＜0.001).However,no significant associations were found for small for gestational age or postpartum hemorrhage.After adjusting for other CMRF abnormalities,the risk of adverse pregnancy outcomes varied among MASLD pregnant women with different CMRF abnormalities:the body mass index abnormal group had higher risks of cesarean section,GDM,PAH,preterm birth,and LGA;the glucose abnormal group had an increased risk of GDM;the blood pressure abnormal group had a higher risk of PAH;the high density lipoprotein cholesterol abnormal group had higher risks of cesarean section,GDM,and PAH;and the tri-glyceride abnormal group was associated with higher risks of GDM and preterm birth.Additional,as the severity of CMRF abnormalities increased,the risks of cesarean section(RR=1.199,95％CI:1.112-1.292,P＜0.001),GDM(RR=1.478,95％CI:1.345-1.624,P＜0.001),PAH(RR=1.626,95％CI:1.367-1.934,P＜0.001),preterm birth(RR=1.384,95％CI:1.120-1.710,P=0.003),and LGA(RR=1.422,95％CI:1.224-1.650,P＜0.001)continued to rise.Conclusion:MASLD during pregnancy is associated with an increased risk of multiple adverse pregnancy outcomes,and the type and severity of CMRF abnormalities significantly influence this association.These results suggest that attention should be paid to the specific CMRF abnormalities when diagnosed MASLD,as this may help to facilitate targeted interventions and reduce the risk of adverse pregnancy outcomes.