BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

Objective:To assess the application effects of an energy-restricted diet combined with high-protein, high-dietary-fiber meal replacement powder and probiotics in overweight/obese adults.Methods:It was a randomized controlled trial. A consecutive sample of 150 overweight/obese adults who underwent physical examinations at the Health Care Center of the First Hospital of Hebei Medical University between November 2021 and March 2022. The participants were randomly assigned into the combined group, the high-protein group, and the common group (50 participants per group) using a random number table method. All three groups of subjects received weight loss health education, energy-restricted diet, and interventions with meal replacement powder and probiotics (or probiotic placebo). The combined group was given high-protein and high-dietary fiber meal replacement powder and probiotics. The high-protein group was given high-protein meal replacement powder and probiotic placebo. The common group was given ordinary meal replacement powder and probiotic placebo. The meal replacement powder was packaged in 35 g per bag, with main components of varying amounts of protein, fat, carbohydrates, vitamins, and trace elements. Both the probiotic powder and the probiotic placebo came in 2 g sachets. The primary components of probiotic powder were various Bifidobacterium, Lactobacillus and excipients, while the main component of probiotic placebo was excipients. The meal replacement powder and the probiotic powder or probiotic placebo were taken twice a day for a total of 12 weeks, one sachet of each time, followed by a 4-week follow-up. The body weight, body mass index, body fat mass, abdominal circumference and hip circumference were measured before the trial (week 0) and at the end of weeks 2, 4, 8, 12, and 16. The change rates of each indicator were calculated. Biochemical indicators, trace elements, and 25-hydroxyvitamin D levels were measured at the end of week 0, 4, 8, and 12. A product evaluation questionnaire was conducted at the end of week 12. A total of 19 cases dropped out due to various reasons. Finally, 46 cases in the combined group, 42 cases in the high-protein group, and 43 cases in the common group were included in the analysis. Paired-samples t test, Kruskal-Wallis H test, one-way analysis of variance, and Mann-Whitney U test were used to compare the differences in weight-loss and maintenance effects, safety and patient acceptance among the three intervention groups, and to analyze the application effect of the energy-restricted diet combined with high-protein and high-dietary fiber meal replacement powder plus probiotics in overweight/obese adults. Results:Among the 131 overweight/obese adults included in the analysis, there were 57 males and 74 females, with a mean age of (37.30±8.33) years. By the end of the week 12, the body mass index [26.87(25.77, 30.38) vs 29.61(27.96, 33.09) kg/m2; 27.10(24.70, 31.37) vs 29.40(27.20, 34.17) kg/m2; 27.98(26.43, 30.12) vs 29.88(28.22, 31.93) kg/m2] and body fat masses [22.15(17.70, 30.15) vs 30.75(25.63, 35.40) kg; 23.35(19.12, 28.70) vs 29.45(26.20, 37.05) kg; 26.80(24.10, 31.60) vs 30.00(26.00, 34.70) kg] in the combined group, the high-protein group and the common group were all lower than those at baseline (week 0) (all P<0.05). At the end of the week 12, the change rates of body fat mass and body mass index in the combined group were both higher than those in the high-protein group and the common group [(25.98%±9.58%) vs (23.88%±11.15%) and (9.35%±11.00%), 9.29%(7.23%, 11.58%) vs 7.96% (5.51%, 10.92%) and 5.77% (2.68%, 10.03%)] (all P<0.05). At the end of the week 12, the body fat mass in the combined group and the high-protein group were both lower than that in the common group [22.15(17.70, 30.15), 23.35(19.12, 28.70) vs 26.80(24.10, 31.60) kg] (both P<0.05). At the end of the week 12, the decreased values of uric acid and high-sensitivity C-reactive protein in the combined group were both higher than those in the high-protein group and the common group [17.15(13.02, 23.45) vs 1.50(0.22, 28.60) and 4.20(0.15, 19.95) μmol/L, 0.43(0.24, 0.60) vs 0.21(0.06, 0.43) and 0.28(-0.04, 0.88) mg/L](both P<0.05). No serious adverse events were observed during the intervention period and at the end of the intervention. In the product evaluation questionnaire, the combined group scored higher than the high-protein group and the common group on items such as usage frequency, taste, satiety, willingness to continue use, willingness to recommend to others, and willingness to purchase [4(3, 4) vs 3(3, 4) and 3(2, 4) points, 4(3, 4) vs 3(3, 4) and 3(2, 4) points, 4(3, 4) vs 3(3, 4) and 3(3, 3) points, 4(3, 4) vs 3(3, 4) and 3(3, 4) points, 4(3, 4) vs 3(3, 4) and 3(3, 3) points, 3(3, 4) vs 3(3, 4) and 3(2, 3) points] (all P<0.05). Conclusion:An energy-restricted diet combined with high-protein, high-dietary-fiber meal replacement powder and probiotics demonstrates superior weight-loss and weight-maintenance effects in overweight/obese adults, with high safety and great user acceptability.

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 establish a model based on the characteristics of breast cancer ultrasound images through deep learning methods to predict the risk of axillary lymph node metastasis（ALNM）in patients with breast cancer（maximum diameter ≤2.5 cm）before surgery.Methods:A total of 419 patients（3 433 breast tumor ultrasound images）with breast cancer（maximum diameter ≤2.5 cm）who underwent axillary lymph node dissection at Beijing Tiantan Hospital，Capital Medical University from January 2019 to December 2024 were retrospectively included. According to the pathological results of axillary lymph nodes，they were divided into 220 cases in the ALNM occurrence group（positive group）and 199 cases in the non-ALNM occurrence group（negative group）. The breast cancer ultrasound images of the two groups of cases were randomly classified into the training set（2 404 images），the validation set（687 images）and the test set（342 images）according to a ratio of 7∶2∶1. YOLOv8 was used as the basic model of You Only Look Once（YOLO）and optimized. The optimized model was applied to locate and capture the potential ultrasound features of breast cancer cases in the training set. A prediction model was constructed based on the captured ultrasound features. The model was adjusted and optimized through the validation set，and then matched with the case images in the test set. The confusion classification matrix graph and the curve graph for measuring the model performance were used to evaluate the model prediction performance and interpret the model，and the efficacy of this model in identifying breast cancer patients at risk of ALNM was analyzed.Results:There were statistically significant differences between the positive and negative groups in terms of the pathological maximum diameter of breast tumors，pathological T staging，the differentiation degree，the presence of distant metastasis，the maximum diameter measured by ultrasound，the quadrant of breast tumor occurrence，the Breast Imaging - Reporting and Data System（BI-RADS）classification of breast tumors，and the presence of abnormal ultrasound features of lymph node（all P<0.05）. The established deep learning model could automatically perform bounding box localization for the breast cancer of patients.The breast tumors in the positive group had potential ultrasound features that could be captured by the model compared with those in the negative group. The mean average precision（mAP）50 was 0.883，mAP 50-95 was 0.636，PR-AUC was 0.884 5，strict PR-AUC was 0.636 4，the sensitivity was 90.5%，and the specificity was 91.2%，and it had a good predictive efficacy. Conclusions:This prediction model based on the ultrasound characteristics of breast cancer through deep learning can effectively predict breast cancer（maximum diameter ≤ 2.5 cm）with the risk of ALNM，providing an effective basis for the clinical management of axillary lymph nodes in breast cancer patients.

Objective To propose a brain electrical phase prediction method based on long short-term memory network(LSTM)to improve the accuracy and robustness of phase synchronization prediction in transcranial magnetic stimulation(TMS).Methods First,an LSTM consisting of an input layer,an LSTM layer,an ReLU activation layer,a fully connected layer and a regression layer was constructed to capture the EEG signal features through the synergistic action of input gates,forgetting gates and output gates.Second,eye-open resting-state EEG data from 30 healthy subjects were trained using the LSTM to obtain a predictive model for EEG signal and EEG phase prediction.Finally,the LSTM method and the traditional autoregressive(AR)method were compared in terms of the phase prediction errors at the overall and individual levels and the prediction performance for peaks and troughs.A regression model was used to explore the relationships between instantaneous EEG amplitude,signal-to-noise ratio and phase prediction error with the LSTM method.Results The LSTM method achieved a total phase prediction error of 0.04°±5.69°,which was lower than that of the traditional AR method(-3.36°±51.13°).For each subject,the LSTM method demonstrated superior phase prediction accuracy compared to the traditional AR method(P＜0.001).The accuracy for predicting peaks(troughs)by the LSTM method(about 89％)was higher than that by the traditional AR method(about 10％).Unlike the traditional AR method,the LSTM method didnot result in linear relationships between instantaneous EEG amplitude,signal-to-noise ratio and phase prediction error,with Pvalues being 0.58 and 0.18,respectively.Conclusion The LSTM-based brain electrical phase prediction method shows high accuracy and robustness when used for EEG phase-synchronized TMS.[Chinese Medical Equipment Journal,2025,46(3):1-8]

Objective:To evaluate the applicability of a new anti-G capability assessment trainer (AG-CAT) in high-performance (HP) anti-G maneuver training and positive pressure breathing for high-G (PHP) training for pilots.Methods:A total of 142 fighter pilots who were subjected to anti-G maneuver training at Dujiangyan Special Crew Sanatorium of PLA Air Force between January and November 2023 were enrolled. According to the Guidelines for Aviation Physiological Training, 123 pilots underwent both HP anti-G maneuver training and PHP positive pressure breathing training, 15 received only HP training, and 4 received only PHP training. Based on the training devices used, these pilots were divided into AG-CAT group and an anti-G and anti-hypoxia capability detection instrument (GHyCDI) group. The 2 groups were compared regarding the pedal force of lower limbs, blood pressure, and improvement of +G z tolerance during training. Results:Of the 138 pilots undergoing HP training, 88 used AG-CAT and 50 used GHyCDI. One hundred and twenty-seven pilots participated in PHP training, with 73 in the AG-CAT group and 54 in the GHyCDI group. During HP training, the pedal force of left lower limbs in the AG-CAT group was greater than that of the right limbs and of the GHyCDI group ( t=4.38, 2.64, P<0.001, =0.009). In PHP training, the AG-CAT group exhibited greater pedal force in left limbs than in right ones, while the GHyCDI group showed an opposite trend ( t=2.25, 3.37, P=0.029, 0.002). Systolic and diastolic blood pressures during HP training (with or without anti-G suits) were higher in the AG-CAT group than in the GHyCDI group ( t=3.50, 3.72, 2.55, 4.21, P=0.001,<0.001,=0.012,<0.001). Similarly, during PHP training, both systolic and diastolic pressures were higher in the AG-CAT group ( t=2.03, 3.81, P=0.045,<0.001). The AG-CAT group demonstrated superior improvements in +G z tolerance during HP training (without/with anti-G suits: Z=2.14, 3.21, P=0.049, 0.001) and PHP training ( Z=2.56, P=0.010) compared with the GHyCDI group. Conclusions:AG-CAT shows excellent applicability in aviation physiological training of pilots. Its ergonomic design, practical functionalities and enhanced compatibility with personnel protective equipment can better meet training requirements compared to conventional devices.

Lentiviral vectors(LVs)are key gene delivery tools for integrating target genes into the host genome,but they may also pose risks of insertional mutagenesis.The vector copy number(VCN)in cells is critical for determining the safety of gene modification.However,the reliability and accuracy of its quantification process are influenced by multiple factors.Developing cell reference materials with specific vector copy numbers represents a viable approach to enhance the reliability and consistency of measurement results,enabling quality control of the quantification process and traceability of outcomes.However,the preparation of such reference materials faces challenges in cell sample design,preparation protocols,and advanced quantification techniques.In this study,T lymphocyte cell line Jurkat-based reference materials with LV gene copy numbers of 1 and 2 copy/cell were developed.A high-precision duplex digital polymerase chain reaction(dPCR)method was established to quantify the LV gene and endogenous genes simultaneously.Additionally,the results of dPCR were cross-validated through next-generation sequencing and flow cytometric analysis.Ultimately,confocal microscopy characterization results showed that the developed cell reference materials had intact morphology.The quantification result of VCN-1 was(1.07±0.11)copy/cell,and that of VCN-2 was(2.09±0.21)copy/cell.These cell reference materials demonstrated compliance with stability and homogeneity requirements,and could be applied for quality control throughout the VCN measurement workflow and metrological traceability,improving the accuracy,comparability,and validity of copy number measurements.

Metal-organic frameworks(MOFs)are a class of organic-inorganic hybrid materials formed by the self-assembly of metal ions or metal clusters with organic ligands through coordination,and possess high specific surface area,tunable pore size and diverse structures.In recent years,MOFs and their composites have shown great application potential in the field of drug detection,especially in selective recognition,enhancing detection sensitivity and on-site rapid detection.This paper summarized the structural characteristics,synthesis methods and detection principles of MOFs and their composites,and reviewed the latest research progresses in detection of various drugs such as opioids,amphetamines,cannabinoids,cathinones,cocaine,ketamine,fentanyls and psychotropic drugs.The advantages and challenges of MOFs materials in the pretreatment of complex biological samples,sensor construction and on-site rapid detection were discussed,and the prospects for future development were analyzed,with the aim of providing theoretical support and technical references for promoting the applications of MOFs in anti-drug practice.