Our previous work revealed that rhomboid domain-containing protein 1 (RHBDD1) participates in the modulation of cell growth and apoptosis in colorectal cancer cells. This study aimed to investigate the function of RHBDD1 in regulating breast cancer progression and its underlying molecular basis. Immunohistochemistry was performed to evaluate RHBDD1 expression in 116 breast cancer tissue and 39 adjacent normal tissue and expression of RHBDD1, phospho-Akt (p-Akt) and cyclin-dependent kinase 2 (CDK2) in the same 84 breast cancer specimens. RHBDD1-knock-out cells were established using breast cancer cell lines. In vitro studies were carried out to estimate the function of RHBDD1 in cell proliferation, migration and invasion. Fluorescence microscopy assay and flow cytometric analysis were used to measure apoptosis and cell cycle regulation. RNA sequencing and western blot analysis were used to investigate the molecular mechanisms of RHBDD1. RHBDD1 was highly up-regulated in breast cancer tissue compared with that in normal tissue and associated with pathological tumor (pT) stage, pathological tumor-node-metastasis (pTNM) stage and estrogen receptor (ER) expression. RHBDD1 up-regulation was associated with poor prognosis in several subtypes of breast cancer. Deletion of RHBDD1 promoted apoptosis and suppressed proliferation, migration and invasion in breast cancer cells. RHBDD1 deletion suppressed Akt activation and decreased CDK2 protein level via proteasome pathway, thus inhibited cell cycle progression and G1/S phase transition. Moreover, the protein level of RHBDD1, p-Akt and CDK2 was significantly positively correlated in breast cancer tissue. Our study reveals that RHBDD1 promotes breast cancer progression by regulating p-Akt and CDK2 protein levels, and might be a potential biomarker and prognostic indicator for breast cancer patients.

The residency matching process has become increasingly competitive across surgical subspecialties, with "interview hoarding" exacerbating resource inefficiencies and systemic inefficiencies in candidate selection. Traditional reliance on non-standardized metrics-particularly USMLE Step 1 scores, institutional prestige, and geographic connections-has further compounded equity concerns in the matching ecosystem. Preference signaling mechanisms have emerged as a standardized solution to enhance both matching efficiency and fairness, though current evidence remains limited by single-specialty studies and insufficient examination of long-term match outcomes. Studies on the preference signaling mechanism in surgical subspecialties published after 2020 were retrieved from PubMed, Embase, and CENTRAL databases. Eleven high-quality retrospective cohort studies involving 10,448 applicants were included. Meta-analysis was performed to compare interview and match rates between signal and non-signal groups, with subgroup analyses assessing the impacts of specialty, data source, and other factors. Totally, eleven studies with 10,488 patients were included for meta-analyses. The interview rate in the signal group was 9.30 times higher than that in the non-signal group (95% CI 7.72-10.89), though substantial heterogeneity was observed across specialties (I² = 96.5%). Orthopedics demonstrated the strongest signaling effect (OR = 18.05), while general surgery showed the weakest (OR = 4.53). Studies based on program directors' data revealed a larger effect size (OR = 34.74). Pooled analysis of four studies showed the match rate in the signal group was 6.76 times higher than that in the non-signal group (95% CI 2.88-10.65), with moderate heterogeneity (I² = 65%). This meta-analysis confirms that the preference signaling mechanism significantly enhances interview rates and match rates in resident matching, demonstrating dual value in optimizing efficiency and promoting equity across surgical specialties. By providing cross-specialty evidence for system optimization, this study advances the preference signaling system toward greater efficiency and fairness in the residency matching process.

Tamoxifen resistance is a common and difficult problem in the clinical treatment of breast cancer (BC). As a novel antitumor agent, Micheliolide (MCL) has shown a better therapeutic effect on tumours; however, little is known about MCL and its role in BC therapy. With tamoxifen stimulation, drug‐resistant BC cells MCF7TAMR and T47DTAMR obtained a high oxidative status and Amidohydrolase 1 (ASAH1) was abnormally activated. The inhibition of ASAH1 rescued the sensitivity of resistant cells to tamoxifen. We found that MCL inhibited the expression of ASAH1 and cell proliferation, especially in MCF7TAMR and T47DTAMR cells. The high oxidative stress status of resistant cells stimulated the expression of ASAH1 by positively regulating AKT, which was restrained by MCL. MCL activated NRF2 by directly binding to KEAP1 and promoting the antioxidant level of tamoxifen‐resistant (TAMR) cells. In addition, ACT001, the prodrug of MCL, significantly inhibited the tumour growth of TAMR cells in preclinical xenograft tumour models. In conclusion, ASAH1 mediates tamoxifen resistance in ER‐positive BC cells. MCL could activate the cellular antioxidant system via NRF2/KEAP1 and inhibit ASAH1 expression through the ROS/AKT signalling pathway, thus suppressing cell proliferation. MCL could be used as a potential treatment for TAMR‐BC.

Pyrotinib is an irreversible pan-ErbB receptor tyrosine kinase inhibitor, designed for the therapy of HER2-positive breast cancers. Inhibition of the epidermal growth factor receptor (EGFR, HER family) efficiently and selectively suppresses the proliferation of human TSC2-deficient smooth muscle cells and reverses lung changes in LAM/TSC. Our pilot study indicated that pyrotinib dramatically restrained the vitality of TSC2-deficient cells compared to its limited impact on TSC2-expression cells. Pyrotinib induced G1-phase arrest and triggered apoptosis by blocking abnormally activated CD24 in TSC2-deficient cells. CD24 is not only an important immune checkpoint, but is also involved in the regulation of signaling pathways. Pyrotinib inhibited the nuclear import of pEGFR and restrained the pEGFR/pSTAT3 signals, which directly boosted the transcriptional expression of CD24 by binding to its promoter region. In reverse, CD24 enhanced pEGFR function by directly binding. Pyrotinib specifically targeted TSC2-deficient cells, inhibited tumor cell viability and induced apoptosis through EGFR-STAT3/CD24 Loop in vivo and in vitro. Thus, pyrotinib may be a promising new therapeutic drug for TSC treatment.

Pre-residency research productivity is widely regarded as a critical factor for medical students aspiring to competitive residency programs. However, its s