In recent years，the emergence of cyclin-dependent kinase 4/6 （CDK4/6） inhibitors has revolutionized the treatment of hormone receptor-positive （HR+） breast cancer. Currently，CDK4/6 inhibitors combined with endocrine therapy （ET） have become the standard first-line treatment for HR+/HER-2- advanced breast cancer，significantly extending progression-free survival （PFS）. However，during first-line treatment，there are some challenges regarding the timing of CDK4/6 inhibitors administration，combination drugs，eligible patient populations，and the application of liquid biopsy. The progression of disease and emergence of drug resistance following CDK4/6 inhibitor treatment have become clinical challenges. Assessing the sensitivity to endocrine therapy and the pattern of disease progression is crucial for determining subsequent treatment strategies for patients. For patients still dependent on endocrine therapy，priority should be given to genetic testing （ESR1，PAM pathway，BRCA mutation） to select targeted inhibitors combined with ET，or cross-line CDK4/6 inhibitors. For those unsuitable for ET，novel antibody-drug conjugates and chemotherapy are preferred options. With the development of more oral selective estrogen receptor down regulators，PI3K inhibitors and additional targets，precision-based individualized treatment will become the future trend.

To investigate the correlation between R-spondin 2 (RSPO2) expression and clinicopathological characteristics in breast cancer，and evaluate its impact on the malignant biological behaviors of breast cancer cell line SKBR-3 in vitro.

RSPO2 expression profiles from 974 breast cancer tissue samples and 113 adjacent normal tissue samples were downloaded from the Cancer Genome Atlas （TCGA） database to analyze difference of RSPO2 expression between cancerous and adjacent normal tissues. Samples were divided into high and low RSPO2 expression groups using the median mRNA expression level as the cutoff value，and the clinicopathological characteristics of patients was compared between two groups. Prognostic implications of RSPO2 in breast cancer patients were evaluated using Kaplan-Meier survival analysis，with survival curves compared via the log-rank test. Functional enrichment and pathway analyses were conducted through Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG）. The mRNA and protein expression levels of RSPO2 in breast cancer cells were determined using RT-PCR and Western blot. SKBR-3 cell lines with RSPO2 knockdown （RSPO2-sh） and negative control （RSPO2-NC） were established via lentiviral transduction. Cellular proliferation，migration，invasion，and apoptosis were evaluated using CCK-8，wound healing，Transwell，and flow cytometry assays，respectively. Expression levels of β-catenin，Cyclin D1，and C-myc were measured by RT-PCR and Western blot. Statistical analyses were performed using the independent sample t test for comparison of quantitative data between two groups，one-way ANOVA for multi-group comparisons，and the LSD test for post-hoc pairwise comparisons.

In both unpaired samples，RSPO2 expression in cancer tissues was significantly higher than that in adjacent non-cancerous tissues ［0.046 （0.022，0.146） vs 0.027 （0.016，0.068），Z=2.751，P=0.006］. In paired samples，RSPO2 expression in cancer tissues was significantly higher than that in corresponding adjacent non-cancerous tissues ［0.022 （0.000，0.076） vs 0.000 （0.000，0.042），Z=-2.200，P=0.028］ breast cancer tissues. Its expression level was significantly correlated with patients' ER status and PR status （P<0.001）. Patients in the high RSPO2 expression group showed significantly lower OS compared with those in the low expression group （HR=1.50，95% CI：1.05-2.14，P=0.024）. GO and KEGG analyses indicated its potential involvement in multiple pathways related to breast carcinogenesis. Results from RT-PCR and Western blot analyses demonstrated differential expression levels of RSPO2 across the T47D，HCC1937，SKBR-3，and JIMT-1 breast cancer cell lines （Western blot： 1.143±0.182，0.980±0.092，2.416±0.059，0.516±0.214，F=46.900，P<0.001； RT-PCR： 1.094±0.075，0.961±0.102，2.634±0.131，0.822±0.221，F=104.912，P<0.001）. Functional assays revealed that compared with the control group （RSPO2-NC），SKBR-3 cells in the RSPO2 knockdown group （RSPO2-sh） exhibited significantly decreased proliferation （0.356±0.037 vs 0.242±0.033，t=4.670，P=0.009），invasion （84.789±8.301 vs 47.203±4.400，t=29.110，P<0.001），and migration capabilities （98.878±6.560 vs 53.670±6.250，t=21.610，P<0.001），and significantly increased apoptosis （18.687±0.460 vs 23.787±0.710，t=11.550，P<0.001）. The expression levels of β-catenin，Cyclin D1，and C-myc were significantly decreased in the RSPO2-sh group compared with the control group （2.266±0.102 vs 1.493±0.150，t=3.540，P<0.05； 1.176±0.051 vs 0.653±0.080，t=8.050，P< 0.001；1.885±0.050 vs 0.860±0.033，t=18.530，P<0.001）.

RSPO2 is highly expressed in breast cancer. High RSPO2 expression is significantly associated with an unfavorable prognosis. RSPO2 may influence the growth and metastatic capabilities of SKBR-3 cells by regulating the Wnt/β-catenin signaling pathway.

To investigate the regulatory B cell (Breg) differentiation in a mouse model of plasma cell mastitis （PCM）.

Fifteen female BALB/c mice were randomly divided into three groups： PCM model group receiving 80 μl intramammary injection of oil in water emulsion containing pathological tissue homogenate from one PCM patient，Freund's adjuvant group receiving complete Freund's adjuvant injection of the same amount into the breast and control group receiving physiological saline injection of the same amount into the breast. HE staining was used to observe the pathological manifestations of mouse breast tissue. Enzyme linked immunosorbent assay （ELISA） was used to detect the expression of inflammatory factors in mouse serum，flow cytometry was used to detect the proportion of Breg in spleen，and immunofluorescence was used to detect the expression of CD21 and CD138 in mouse breast tissue. Continuous data were compared among multiple groups using analysis of variance，and pairwise comparisons were conducted using the LSD test.

The HE staining results showed plasma cell infiltration in the breast tissue of mice in the PCM model group. The ELISA results showed that the expressions of inflammatory factors IL-10，TNF-α，IL-6，IL-35 and IL-1β in the PCM model group mice were significantly higher than those in the control group and Freund's adjuvant group （all P<0.001）. The flow cytometry results showed that the proportion of CD19⁺CD5^-CD1d⁺IL10⁺ Breg in the PCM model group was significantly higher than that in the control group and Freund's adjuvant group （24.66% vs 3.09%，P<0.001； 24.66% vs 2.53%，P<0.001），and the proportion of CD19⁺CD5⁺CD1d⁺IL10⁺ Breg was significantly increased compared with the control group and Freund's adjuvant group （11.66% vs 2.92%，P<0.001； 11.66% vs 1.93%，P<0.001）. The proportion of CD21 positive cells in the breast tissue of mice in the PCM model group was significantly increased compared with the control group and Freund's adjuvant group （36.45% vs 16.77%，P<0.001； 36.45% vs 16.47%，P<0.001），and the proportion of CD138 positive cells was significantly increased compared with the control group and Freund's adjuvant group （17.18% vs 7.33%，P<0.001； 17.18% vs 7.48%，P<0.001）.

The PCM mouse model shows abnormal differentiation of Breg.

To compare the clinical efficacy between axillary liposuction combined with single-port endoscopic subcutaneous mastectomy and traditional periareolar subcutaneous mastectomy in the treatment of gynecomastia （GM），and assess postoperative satisfaction.

A retrospective analysis was conducted on the clinical data of 55 patients with GM who underwent surgical treatment in the Changzhou First People's Hospital from January 2023 to August 2024. According to the surgical approach，the patients were divided into the endoscopic surgery group （receiving axillary liposuction combined with single-port endoscopic subcutaneous mastectomy，23 cases） and the traditional surgery group （receiving traditional periareolar subcutaneous mastectomy，32 cases）. The two groups were compared in terms of incision length，intraoperative blood loss，operation duration，extubation time，hospital stay and complication rate. At 3 months postoperatively，the BODY-Q scale was adopted to assess postoperative satisfaction from six dimensions，including chest，nipple，scar，body image，social interaction，and appearance-related distress. For the comparison of normally distributed continuous data between groups，the independent sample t test was used. For the comparison of non-normally distributed continuous data between groups，nonparametric test was adopted. For the comparison of categorical data between groups， χ² test or Fisher's exact test was employed.

The incision length in the endoscopic surgery group was significantly shorter than that in the traditional surgery group ［3.0 （3.0，3.0） cm vs 4.0 （3.5，4.0） cm，Z=-5.574，P<0.001］.The endoscopic surgery group had significantly less intraoperative blood loss ［unilateral： （11.7±2.9） ml vs （24.3±7.3） ml，t=-2.813，P=0.023； bilateral： （20.4±6.5） ml vs （32.2±8.3） ml，t=-5.206，P<0.001］，and significantly shorter extubation time compared with the traditional surgery group ［（3.4±0.6） d vs （4.0±0.8） d，t=-2.969，P=0.004］，while the operation time was significantly longer ［unilateral： （100±20） min vs （50±16） min，t=4.228，P=0.003； bilateral： （215±31） min vs （94±27） min，t=13.957，P<0.001］. there were no significant differences in hospital stay or complication incidence between the two groups ［（3.9±0.9） d vs （3.7±1.3） d，t=0.695，P=0.490； 17.4%（4/23) vs 9.4%（3/32），P=0.435］. The results of BODY-Q scale assessment showed the scar score was 77±13 in the endoscopic surgery group and 66±12 in the traditional surgery group，indicating a significant difference （t=3.130，P=0.003），and no significant difference was observed in scores of chest，nipple，body image，social interaction，and appearance-related distress dimensions between the two groups （all P>0.05）.

Axillary liposuction combined with single-port endoscopic subcutaneous mastectomy brings better clinical outcome and postoperative patient satisfaction in GM patients compared with traditional periareolar subcutaneous mastectomy.

To investigate the role and mechanism of the m6A-dependent IGF2BP2/CCNB2 axis in the progression of triple negative breast cancer (TNBC).

Tumor and adjacent normal tissue specimens were collected from 30 TNBC patients who underwent surgery in the Department of Breast and Thyroid Surgery, the First Affiliated Hospital of Army Medical University between May 2020 and April 2023. Human normal breast epithelial cell line MCF-10A and TNBC cell lines (MDA-MB-231, MDA-MB-468, BT-549, HCC1806, and MCF-10A) were used. Real-time quantitative RT-PCR was used to measure IGF2BP2 mRNA between tumor tissue and adjacent normal tissue, and among different cell lines. The MDA-MB-231 cells were transfected with the IGF2BP2 overexpression plasmid (OE-IGF2BP2 group), IGF2BP2 siRNA sequence (si-IGF2BP2 group), wild-type CCNB2 reporter plasmid pmirGLO-CCNB2-WT and empty vector OE-NC (WT+NC group), wild-type CCNB2 reporter plasmid pmirGLO-CCNB2-WT and IGF2BP2 overexpression plasmid OE-IGF2BP2 (WT+OE group), mutant-type CCNB2 reporter plasmid pmirGLO-CCNB2-Mut and empty vector OE-NC (Mut+NC group), mutant-type CCNB2 reporter plasmid pmirGLO-CCNB2-Mut and IGF2BP2 overexpression plasmid OE-IGF2BP2 (Mut+OE group), IGF2BP2 overexpression plasmid and CCNB2 siRNA (OE+si-CCNB2 group). Real-time quantitative RT-PCR was used to measure IGF2BP2 mRNA expression in each group. Cell proliferation assays were used to measure optical density; Transwell assays were used to assess cell migration and invasion; dual-luciferase reporter were used to detect the ratio of luciferase activity of wild-type and mutant m6A sites on CCNB2 mRNA. The methylated RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) were used to validate the binding activity between IGF2BP2 and CCNB2. The continuous data were compared between two groups using t tests; among multiple groups using one-way ANOVA and pairwise comparisons by Tukey's test. The mRNA expression levels of two factors between tumor tissue and adjacent tissues were compared by paired t test; multiple-group comparisons at different time points were analyzed by repeated measures analysis of variance with pairwise comparison by Tukey's test. The correlation between IGF2BP2 and CCNB2 mRNA expression was analyzed by Spearman method.

IGF2BP2 mRNA expression in adjacent normal tissue was significantly higher than that in TNBC tumor tissue (1.58±0.59 vs 6.51±1.83, t=15.620, P<0.001). The IGF2BP2 mRNA expression in patients with regional lymph node metastasis (n=19) was significantly higher than that in those without (n=11) (4.62±1.03 vs 7.61±1.16, t=7.075, P<0.001). The IGF2BP2 mRNA expression in stage Ⅲ–Ⅳ breast cancer patients (n=22) was significantly higher than that in stage Ⅰ–Ⅱ breast cancer patients (n=8) (7.34±1.31 vs 4.24±0.77, t=6.261, P<0.001). The IGF2BP2 mRNA expression in MCF-10A and TNBC cell lines (MDA-MB-231, MDA-MB-468, BT-549, HCC1806) was 1.09±0.11, 4.34±0.20, 2.25±0.17, 1.67±0.16, and 3.18±0.09, respectively, indicating a significant difference (F=281.70, P<0.001). The IGF2BP2 mRNA expression was significantly higher in OE-IGF2BP2 group than in control group (3.32±0.18 vs 1.05±0.06, t=23.610, P<0.001); lower in si-IGF2BP2 group than in control group (0.33±0.04 vs 0.66±0.05, F=81.310, P<0.001). The optical density values in control, OE-IGF2BP2 and si-IGF2BP2 groups showed a significant difference (between groups: F=300.00, P<0.001; time points: F=947.20, P<0.001; interaction: F=45.390, P<0.001); migration cell counts were 186.30±8.08, 254.70±6.03, 122.70±8.62, respectively, indicating a significant difference (F=222.80, P<0.001); invasion cell counts were 152.70±11.02, 222.70±9.45, 81.67±7.02, respectively, indicating a significant difference (F=172.10, P<0.0001); CCNB2 mRNA expression was 1.05±0.07, 2.95±0.07, 0.62±0.04, respectively, indicating a significant difference (F=1193, P<0.001); CCNB2 mRNA stability differed significantly among groups (between groups: F=72.430, P<0.001; time points: F=511.30, P<0.001; interaction: F=23.930, P<0.001). CCNB2 mRNA expression in TNBC tissue was significantly higher than that in adjacent tissue (5.03±1.62 vs 1.42±0.49, t=13.140, P<0.001), and CCNB2 mRNA expression was positively correlated with IGF2BP2 mRNA (r=0.7043, P<0.001). The ratio of luciferase activity in WT+OE group were significantly higher than that in control group (12.33±1.11 vs 5.33±0.79, t=8.895, P<0.001). The methylated CCNB2 enrichment was significantly increased in the anti-m6A group (t=15.94, P<0.001), and CCNB2 enrichment was also elevated in the anti-IGF2BP2 group (t=19.61, P<0.001). The optical density values in control, OE+si-NC, and OE+si-CCNB2 groups showed a significant difference (between groups: F=122.40, P<0.001; time points: F=2279.000, P<0.001; interaction: F=24.530, P<0.001); migration cell counts were 144.00±4.58, 258.00±5.29, and 175.00±8.89, respectively, indicating a significant difference (F=244.300, P<0.001); invasion cell counts were 113.30±11.50, 214.70±7.37, and 152.70±9.71, respectively, indicating a significant difference (F=83.590, P<0.001).

IGF2BP2 enhances the stability of CCNB2 mRNA in an m6A-dependent manner, thus promoting proliferation, migration, and invasion of TNBC cells.