BACKGROUND:Subarachnoid hemorrhage (SAH) is an acute neurological disorder with high mortality and disability, particularly among older adults. Using data from Global Burden of Disease (GBD) 2021 study, we comprehensively assessed the global, regional, and national burden of SAH in older populations from 1990 to 2021 and projected future trends to 2050. METHODS:Data on SAH prevalence, incidence, mortality, and disability-adjusted life years (DALYs) were extracted for adults aged ≥ 60  years. Temporal trends were evaluated using estimated, annual, and average annual percentage changes (EAPC, APC, AAPC). Correlation, decomposition, frontier, predictive, and inequality, and risk factor analyses were applied to evaluate burden patterns. RESULTS:From 1990 to 2021, absolute prevalent and incident cases increased, whereas all age-standardized rates (ASRs) declined globally (EAPC < 0). The middle-socio-demographic index (SDI) region showed the greatest reduction, while Oceania had the highest age-standardized mortality (ASMR) and DALY (ASDR) rates. East Asia, particularly China, showed the steepest declines. SAH burden was concentrated in ages 60-75 group and higher in women; later cohorts exhibited lower risk. Population growth was the main driver of global increases in case and deaths, while epidemiological changes partially offset these increases and led to a net decline in DALYs. High systolic blood pressure remained the leading risk factor. Health inequalities widened, and frontier analysis revealed performance gaps among some high-SDI countries. Bayesian Age-Period-Cohort (BAPC) model projected rising absolute cases but continued declines in all ASRs by 2050. CONCLUSION:SAH burden among older adults shows regional, demographic, and developmental disparities. Despite progress, population aging demands sustained health-system strengthening to mitigate future burden.

Patient-derived organoids (PDOs) have been demonstrated not only to predict the response to neoadjuvant chemotherapy but also to tailor the treatment options for advanced breast cancer to improve prognosis. Here, we first reported a case of breast cancer liver metastasis that obtained clinical complete response (cCR) after treatment with eribulin and capecitabine, which showed sensitivity in the organoid drug sensitivity testing, and we conducted a systematic literature review. Our case report further provides a scientific basis for the PDOs as a powerful preclinical model to predict individual treatment sensitivity and improve the treatment outcomes of patients with advanced breast cancer, especially those with refractory or heavily treated breast cancer.

Breast cancer is the most common malignancy among women worldwide and exhibits marked heterogeneity. Among its various subtypes, triple-negative breast cancer (TNBC) is associated with an inferior prognosis. Although molecular stratification tools such as Oncotype DX and MammaPrint have been adopted in clinical settings, prognostic models based on chromosomal instability remain inadequate. The centromere protein (CENP) family, as a key regulator of genomic stability, has been closely linked to tumor progression due to its aberrant expression. In this study, we integrated multi-omics data—including RNA transcriptomic profiles and single-cell RNA sequencing—and employed weighted gene co-expression network analysis (WGCNA) to identify core gene modules associated with CENPA. A prognostic risk model was developed using Cox regression analysis and the LASSO algorithm. Validation in independent cohorts demonstrated that the model effectively stratified patients into high- and low-risk groups, with the high-risk group showing significantly reduced five-year survival (p < 0.001). Furthermore, the single-cell analysis revealed that CENPA-high subpopulations were enriched in proliferative tumor cells and were associated with an immunosuppressive tumor microenvironment. This study is the first to systematically construct a CENP-based prognostic model for breast cancer, providing novel molecular biomarkers and potential therapeutic targets for personalized treatment. The biological function of the key molecule MMP1 in breast cancer was further validated through both in vitro and in vivo experiments.

Supplementary Fig. S1 to S16 for multiple Supplementary Figures. Supplementary Table S1 to S9 for multiple Supplementary Tables

Background Ependymoma is a rare central nervous system tumor with substantial heterogeneity in anatomical site, histology, and clinical outcome 1–3 . Population-based evidence on temporal changes in survival remains limited, and up-to-date estimates are particularly needed 4,5 . We therefore used model-based period analysis to evaluate temporal trends in relative survival and to generate short-term forecasts in patients with ependymoma 6,7 . Methods Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database 8 (Incidence – SEER Research Data, 17 Registries, Nov 2024 Sub). Patients diagnosed during 2000–2019 with ICD-O-3 histology/behavior codes 9391/3, 9392/3, 9393/3, and 9394/3 and primary sites restricted to C71.* and C72.0–C72.1 were included. Five-year relative survival (RS) was estimated using period analysis 9,10 ; expected survival was derived using the Ederer II method 11 , and standard errors were calculated using Greenwood’s formula. Diagnosis periods were grouped as 2000–2004, 2005–2009, 2010–2014, and 2015–2019. Temporal trends were assessed across diagnosis-period mid-years on the absolute survival scale. Given that only four observed diagnosis periods were available, Joinpoint analysis was used only to assess whether an overall linear trend was present, rather than to identify multiple slope changes. Short-term forecasts for 2020–2024 were generated using inverse-variance-weighted models based on the observed period estimates. Results The baseline descriptive cohort included 4,070 patients, and the RS analytic cohort included 3,770 patients. Overall 5-year RS increased from 81.7% in 2000–2004 to 89.5% in 2015–2019. Period-specific estimates supported a significant upward linear trend over time. Non-anaplastic ependymoma showed consistently high 5-year RS, increasing from 86.1% to 94.4%, whereas anaplastic ependymoma showed lower but improving RS, increasing from 55.1% to 74.1%. Temporal improvement was more pronounced in anaplastic disease than in non-anaplastic disease. Model-based short-term forecasts suggested that overall 5-year RS may continue to improve in 2020–2024. Spinal/cauda equina tumors showed persistently favorable survival, whereas infratentorial and other intracranial tumors had lower RS with gradual improvement. In supplementary stage analyses, localized disease consistently showed better RS than non-localized disease. Conclusions Model-based period analysis showed a steady improvement in 5-year relative survival for ependymoma from 2000–2004 to 2015–2019. Short-term forecasts suggested that this favorable pattern may extend into 2020–2024, although prognostic heterogeneity remained evident across major clinicopathological subgroups.

ObjectiveTo compare long-term survival in early-stage breast cancer patients treated with different radiation therapy modalities.MethodsData was retrospectively derived from SEER database. We compared overall survival (OS), breast cancer specific survival (BCSS) and second primary malignancies (SPM) in early-stage breast cancer patients treated with postoperative radiotherapy (PORT) versus those treated neoadjuvant radiotherapy (NART) and intraoperative radiotherapy (IORT) after propensity score matching by 1:1.ResultsA total of 457,166 patients were included in this study. After matching, the 20-year OS of 1441 patients in NART cohort was lower than that in PORT cohort (p < 0.01), particularly in hormone receptor positive patients (p < 0.01). NART were dependent prognostic factors for 20-year OS [Hazard Ratio (HR):1.21, 95%CI: 1.06-1.38, p < 0.01). No significant difference in BCSS was observed between NART and PORT treatments. Additionally, patients undergoing NART had a lower risk of all SPM (p = 0.01) and second solid cancers (p = 0.02) but a comparable risk of second hematological malignancies (p = 0.55) than patients administered PORT. HR-positive was a risk factor for SPM. No OS, BCSS or SPM risk difference were significantly observed in the 2096 pairs of IORT and PORT groups.ConclusionCompared to PORT, NART and IORT don't offer survival advantages for early-stage breast cancer patients. Altering the sequence of radiotherapy requires careful evaluation.

BACKGROUND:Suspicious calcifications in breast cancer (BC) often limit eligibility for breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC). This study assessed the impact of ductal carcinoma in situ (DCIS) status and post-NAC imaging changes on pathological complete response (pCR), BCS feasibility, and prognosis. METHODS:We retrospectively analyzed 163 BC patients with suspicious calcifications treated with NAC (median follow-up, 38.9 months). Logistic regression identified predictors of pCR, associations between calcification changes and pCR were assessed using Cramer's V, and OS and DFS were evaluated using Kaplan-Meier analysis. RESULTS:73 patients had DCIS and 90 had non-DCIS. Calcification reduction after NAC was more frequent in non-DCIS group (56.7%; p = 0.012). pCR rates were higher in non-DCIS group than in DCIS group (73.7% vs 26.3%; p = 0.015). After adjustment, DCIS was associated with reduced pCR rates (OR: 0.26, 95% CI: 0.08-0.73). Overall BCS rate was 11%. Calcification reduction showed a weak correlation with pCR (Cramer's V = 0.321). No significant OS, DFS, or BCS differences were observed by DCIS status or calcification change within follow-up. CONCLUSION:DCIS is associated with reduced pCR after NAC. Calcification findings alone should be interpreted cautiously, and BCS feasibility should be assessed using comprehensive surgical criteria.

BACKGROUND:Central nervous system (CNS) ependymoma is a heterogeneous tumor with highly variable clinical behavior. Most existing prognostic models primarily focus on overall survival, whereas robust tools specifically predicting cancer-specific survival (CSS) in CNS ependymoma are lacking. We aimed to develop a Surveillance, Epidemiology, and End Results (SEER)-based nomogram for individualized prediction of CSS in patients with CNS ependymoma. METHODS:We identified patients with primary CNS ependymoma (2010-2022) from the Surveillance, Epidemiology, and End Results (SEER) database. The cohort was randomly split in a 7:3 ratio into training and validation cohorts; patients were assigned using a computer-generated random number sequence. Multivariable Cox proportional hazards regression was used to identify independent prognostic factors. A nomogram was constructed to predict 3-, 5-, and 8-year CSS. Model performance was evaluated using the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA), and was compared with a SEER summary stage-only model. RESULTS:The study included 1744 patients with CNS ependymoma. During a median follow-up of 63 months, the 3-, 5-, and 8-year CSS rates were 92.4%, 90.5%, and 86.7%, respectively. Multivariable analysis identified age, sex, histologic subtype, primary tumor site, and SEER summary stage as independent predictors of CSS. The nomogram demonstrated superior discrimination, with C-indices of 0.818 in the training cohort and 0.827 in the validation cohort, significantly outperforming the stage-only model (0.588 and 0.547, respectively). Similarly, the nomogram yielded higher areas under the curve (AUCs) at all time points (e.g., 5-year AUC: 0.850 vs. 0.600 in the training cohort). Calibration plots showed excellent agreement between predicted and observed CSS, and DCA indicated a higher net clinical benefit for the nomogram than for the stage-only model across a broad range of threshold probabilities. CONCLUSIONS:We developed and internally validated a robust, CSS-oriented nomogram for CNS ependymoma using a contemporary, population-based cohort. This tool outperformed conventional staging systems and may provide a practical approach for individualized risk stratification and clinical decision-making in patients with CNS ependymoma.

Background:Breast cancer is the most common malignancy and a leading cause of cancer-related deaths among women worldwide. Although treatment advances have improved outcomes, the 5-year survival rate for metastatic breast cancer remains low. Understanding the anatomical distribution, associated risks, and prognostic features of metastases in patients with newly diagnosed stage IV breast cancer is essential for improving clinical management. This study aims to comprehensively investigate these aspects using data from the SEER database. Methods:This study utilized a retrospective cohort design, examining data from the Surveillance, Epidemiology, and End Results (SEER) database. The investigation considered patients diagnosed with stage IV breast cancer from SEER database. Using logistic regression, odds ratios (ORs) were calculated to determine the risk of various metastases, stratified based on sociodemographic and clinicopathological variables. Survival analyses were executed with Kaplan-Meier methodology in tandem with Cox regression analyses. Results:Out of 356,789 breast cancer patients considered, 18,036 (5.06%) were diagnosed with de novo stage IV disease. Bone metastasis predominated with a composition ratio of 42.6%. Patients with the HR-/HER2+ subtype exhibited the highest metastasis incidence at the time of diagnosis, constituting 8.7% of the entire cohort. Male patients displayed heightened susceptibility to bone, lung, and brain metastases compared to female counterparts. Hispanic individuals exhibited the highest propensity for brain metastases. Relative to other subtypes, the HR-/HER2- patients were more inclined toward lung metastases. Those with bone metastasis had a median survival period of 27 months. Grade III patients with brain or liver metastases faced the most adverse prognoses. A comprehensive profile detailing metastasis patterns by demographics, tumor site and stage, biology, and treatment was presented. Conclusions:This study represents the most comprehensive analysis of metastasis' anatomical distribution and prognosis in breast cancer, offering invaluable insights into metastatic tendencies and characteristics.

Tall Cell Carcinoma with Reversed Polarity (TCCRP) is a rare and distinct subtype of invasive breast carcinoma, first described in 2003. It is histologically characterized by tall columnar epithelial cells with reversed nuclear polarity and shares morphological features with papillary thyroid carcinoma (PTC). However, its unique molecular signature, including IDH2 and PIK3CA mutations, differentiates it from other breast cancer subtypes. A retrospective systematic study of 91 published cases of TCCRP was conducted, including two cases from our institution. Clinical, pathological, molecular, and treatment-related data were collected and analyzed. Descriptive statistics and Kaplan-Meier survival analysis were employed to evaluate disease-free survival (DFS) and overall survival (OS). Subgroup analyses explored associations between clinical features, molecular markers, and outcomes. The median age at diagnosis was 64 years, with a predominance of small tumors (mean size: 10.4 mm, T1 stage). Histologically, hallmark features included reversed nuclear polarity (100 %), nuclear grooves, and intranuclear pseudoinclusions. Immunohistochemical analysis confirmed a triple-negative profile (ER-/PR-/HER2-) in most cases, with consistent breast-specific marker expression (GATA3, CK7). Molecular testing revealed frequent IDH2 R172 (84.6 %) and PIK3CA (72.5 %) mutations. Surgical management, predominantly breast-conserving surgery (BCS), was the primary treatment, with adjuvant therapies rarely utilized. At a median follow-up of 35.8 months, recurrence occurred in only 2.2 % of cases, and the overall survival rate was 100 %. TCCRP is a rare, low-grade breast cancer subtype with a favorable prognosis and low recurrence risk based on currently available data, but longer follow-up studies are needed to confirm this observation. Its distinct histological and molecular features enable accurate diagnosis and differentiation from other breast cancers and metastatic thyroid carcinoma. Given its indolent nature, conservative treatment strategies, including BCS, are effective, and adjuvant therapies can be minimized. Future research should explore targeted therapies for IDH2 and PIK3CA mutations to expand treatment options for this unique subtype.

BACKGROUND:Angiosarcoma, a rare and highly aggressive malignancy originating from vascular endothelial cells, is characterized by its rapid progression, high invasiveness, and poor prognosis. Due to the limited understanding of its tumor microenvironment (TME) and the absence of effective treatments, further research is essential to elucidate its pathogenic mechanisms and improve therapeutic strategies. OBJECTIVE:This study aims to characterize the cellular heterogeneity and unique TME of primary breast angiosarcoma using single-cell RNA sequencing (scRNA-seq), to identify potential therapeutic targets and improve clinical outcomes. METHODS:Tumor samples were obtained from a patient with bilateral primary breast angiosarcoma and two patients with invasive breast cancer. Single-cell RNA sequencing (scRNA-seq) was conducted to capture the transcriptomic profiles of individual cells within the tumor samples. Following stringent quality control, a total of 31,771 cells were analyzed using comprehensive bioinformatics approaches. Cell populations were identified and classified into distinct cell types, and differential gene expression analysis was performed to explore key signaling pathways. Functional enrichment analysis was used to identify pathways related to tumor progression and immune evasion. Additionally, cell-cell communication networks were mapped to understand interactions within the TME, with a focus on pathways that may serve as therapeutic targets. RESULTS:The scRNA-seq analysis revealed significant differences in the distribution of perivascular cells, fibroblasts, T cells, endothelial cells, and myeloid cells in breast angiosarcoma compared to invasive breast cancer. Key pathways enriched in angiosarcoma samples included growth factor binding, platelet-derived growth factor binding, and ribosome biogenesis, with abnormal expression of several ribosomal proteins. Notably, genes such as FAT4, KDR, FN1, and KIT were highly expressed in angiosarcoma endothelial cells, correlating with poor prognosis. Cell communication analysis highlighted the CXCL12-CXCR4 axis as a crucial mediator of the TME in angiosarcoma. CONCLUSION:This study provides critical insights into the TME of primary breast angiosarcoma, highlighting potential molecular targets and pathways for therapeutic intervention. These findings may inform the development of more effective treatment strategies for this rare and challenging tumor type.

BackgroundBreast cancer (BC) is the most common malignancy among women and shows significant heterogeneity in its prognosis. Among the subtypes, triple-negative breast cancer (TNBC) has the poorest prognosis. Despite advancements in molecular stratification tools, such as Oncotype DX and MammaPrint, prognostic models based on chromosomal instability are still insufficient. The centromere protein (CENP) family, which plays a crucial role in maintaining genomic stability, is associated with tumor progression due to aberrant expression.MethodsIn this study, we integrated multi-omics data, including RNA transcriptomic profiles and single-cell RNA sequencing, to identify gene modules linked to CENPA using weighted gene co-expression network analysis (WGCNA). We developed a prognostic model employing Cox regression and the LASSO algorithm. Validation was performed on independent cohorts, and the model's performance was tested by stratifying patients into high- and low-risk groups based on their five-year survival rates (p < 0.001).ResultsThe prognostic model effectively identified high- and low-risk patient groups, with the high-risk group showing significantly reduced five-year survival. Single-cell analysis revealed that CENPA-high subpopulations were enriched in proliferative tumor cells and were associated with an immunosuppressive tumor microenvironment.ConclusionThis study is the first to establish a CENP-based prognostic model for BC, offering novel biomarkers and potential therapeutic targets for personalized treatment. Additionally, the biological function of the key molecule MMP1 was validated through both in vitro and in vivo experiments.

Objective: The current study aims to investigate the prognostic value of breast cancer integrated oxidative stress score (BCIOSS) in patients with breast cancer who received neoadjuvant chemotherapy (NACT). Methods: A retrospective analysis of 104 breast cancer patients who underwent NACT from June 2009 to December 2015 was performed. The differences of BCIOSS of breast cancers in regard to variables were analyzed using Chi-square test and Fisher's exact test. The Kaplan-Meier method was used to evaluate survival curve between low BCIOSS group and high BCIOSS group, and the two groups were compared by Log-rank tests at the individual index level. The univariate and multivariate Cox regression analyses were established by the important predictive factors determined based on univariate analysis. The nomograms were further conducted based on the factors by the multivariate analyses. Results: Patients were assigned to low BCIOSS group (BCIOSS≤2.54) or high BCIOSS group (BCIOSS>2.54) via ROC curve. BCIOSS was a latent prognostic factor for patient survival [DFS; hazard ratio (HR): 0.163, 95%CI: 0.045-0.596, P=0.006; and OS; HR: 0.168, 95%CI: 0.056-0.500, P=0.001]. Patients with a high BCIOSS had longer survival time than those with a low BCIOSS (DFS: χ2=7.317, P=0.0068; and OS: χ2=9.407, P=0.0022). Calibration curves shown that the predicted line conformed well to the reference line for the 5-year survival category. DCA revealed that the nomograms conducted had a better clinical predictive application than only by BCIOSS. Conclusion: BCIOSS is a latent prognostic factor, and patients with high oxidative stress scores have a better prognosis and longer survival time.

BACKGROUND:Oncoplastic breast-conserving surgery (OBCS) improves satisfaction in patients who would fare otherwise sub-optimal cosmetic outcomes while bringing challenges in tumor-bed identification during adjuvant radiotherapy. The ultra-hypofractionated breast radiotherapy further shortens treatment sessions from moderately hypofractionated regimens. To circumscribe the difficulty in tumor-bed contouring and the additional toxicity from larger boost volumes, the authors, propose to move forward with the boost session preoperatively from the adjuvant radiation part. Thus, the present study aims to evaluate the feasibility of a new treatment paradigm of preoperative primary-tumor boost before breast-conserving surgery (BCS) or OBCS followed by adjuvant ultra-hypofractionated whole-breast irradiation (u-WBRT) for patients with early-stage breast cancer. METHODS:There was a phase II study. Patients younger than 55 years old, with a biopsy confirmed mono-centric breast cancer, without lymph node involvement were enrolled. A preoperative primary-tumor boost was given by a single 10 Gy in 1 fraction, and BCS or OBCS was conducted within 2 weeks afterwards. Adjuvant u-WBRT (26 Gy/5.2 Gy/5 f) was given in 6 weeks postoperatively without any boost, after the full recovery from surgery. Surgical complications and patient-reported outcomes, as assessed via Breast-Q questionnaires, were documented. A propensity score matching approach was employed to identify a control group at a 1:1 ratio for BREAST-Q outcomes comparison. RESULTS:From May 2022 to September 2023, 36 patients were prospectively enrolled. Surgical complications were observed in seven cases (19.4%), including three cases with Clavien-Dindo (CD) grade 1-2 and four cases with CD grade 3 complications. All but four patients (11.1%) started the planned u-WBRT within 1 week after the predefined due dates postoperatively (≤49 days). Four patients (11.1%) developed grade 2 radiodermatitis after chemotherapy initiation. Compared to the study group, the control patients reported higher scores in chest physical well-being ( P =0.045) and in their attitudes towards arm swelling ( P =0.01). No significant difference was detected in the other of domains (Satisfaction with Breasts, Sexual and Psychosocial Well-Being, and Adverse Effects of Radiation). With a median follow-up period of 9.8 months (2.4-18.9 months), none had any sign of relapse. CONCLUSION:This Phase II clinical trial confirmed the technical and safety feasibility of a novel radiation schedule in patients undergoing BCS or OBCS. According to the BREAST-Q questionnaire, patients who underwent novel radiation schedules reported lower satisfaction in chest physical well-being. A randomized controlled trial is necessary to further investigate these findings. Additionally, long-term follow-up is required to assess oncological outcomes.

OBJECTIVE:To compare dosimetric differences between intensity-modulated proton therapy (IMPT) and photon-based radiotherapy (VMAT/IMRT) in the treatment of skull base tumors, focusing on target coverage and organ-at-risk (OAR) sparing. METHODS:All patients with skull base tumors who underwent proton therapy between December 2021 and August 2022 were included in this study. For each case, both IMPT and VMAT/IMRT plans were generated using Eclipse TPS, with robust optimization applied for protons. Dosimetric metrics for target volumes and OARs-including the brainstem, spinal cord, visual pathways, eyes, lenses, and salivary glands-were extracted and compared. Key endpoints included D 2 % $D_{2\%}$ , D mean $D_{\text{mean}}$ , conformity index (CI), and homogeneity index (HI). Statistical comparisons were performed using non-parametric Wilcoxon signed-rank tests, with significance set at p<0.05. RESULTS:Target coverage was comparable between IMPT and photon plans ( D 98 % $D_{98\%}$ of 57.51 ± $\pm$ 6.14 Gy for photon and 58.06 ± $\pm$ 5.85 Gy for proton, p = 0.12, respectively). IMPT provided statistically significant dose reductions to brainstem, spinal cord, lenses, eyes, and the right parotid. The brainstem D 2 % $D_{2\%}$ was reduced from 45.70 ± $\pm$ 11.49 Gy of photons to 39.47 ± $\pm$ 13.03 Gy of protons (p = 0.037). Dose reductions of ∼ $\sim$ 29%-83% were observed for other above OARs. Although no significant difference was found in doses to the left parotid or visual pathways, substantial dose reductions were observed in individual cases. CONCLUSION:IMPT achieved equivalent target coverage to VMAT/IMRT while offering superior sparing of several critical OARs. These findings support the clinical potential of IMPT in the management of anatomically complex skull base tumors, particularly when normal tissue preservation is a key concern.

BACKGROUND: Predicting rupture risk in small intracranial aneurysms (IAs) < 5 mm is crucial for guiding clinical decisions. This study aims to identify key clinical and morphological risk factors associated with rupture in small IAs, providing better insight for decision-making. METHODS: A retrospective analysis was performed on patients with small IAs from one center, with external validation data from another center. Logistic regression identified significant risk factors for aneurysm rupture, which were incorporated into a predictive model. The model's performance was evaluated using the area under the receiver operating characteristic curve, calibration plots, and the Hosmer-Lemeshow goodness-of-fit test. Clinical utility was assessed via decision curve analysis. RESULTS: The training cohort consisted of 226 patients (ruptured, n = 181; unruptured, n = 92), while 136 patients (ruptured, n = 100; unruptured, n = 59) were used for external validation. Significant risk factors included hypertension, smoking, anterior communicating artery aneurysms, daughter sacs, aspect ratio, and size ratio. The model demonstrated strong predictive ability with area under the curves of 0.969 and 0.967 in the training and validation cohorts, respectively. Calibration plots indicated a good agreement between predicted and observed rupture risks, while decision curve analysis highlighted the model's clinical relevance. CONCLUSION: This study identifies and validates critical risk factors associated with small IA rupture and presents a clinically useful, high-accuracy predictive model to aid in individualized patient management.

Human umbilical cord mesenchymal stem cells (hUMSCs) are considered an effective prospect for treating TBI, but they tend to accumulate in the lungs after intravenous injection, hindering further clinical translation. Brahma-related gene 1(BRG1) can be influenced by estrogen to regulate adhesion, and ourprevious studies have found that the expression of BRG1 in lungs increases after TBI. However, the relationship between BRG1, estrogen, TBI, and stem cell lung aggregation is not clear. By regulating the expression levels of BRG1 in vascular endothelial cells and hUMSCs, Western Blot and immunohistochemistry were used to explore its changes in adhesion and possible mechanisms; used in vivo bioluminescenece imaging analysis, real-time tracking the distribution of stem cells after transplantation; and therapeutic drug E2 is introduced to observe the effect of changes in BRG1 expression on the aggregation of hUMSCs in the lungs of model animals, as well as the therapeutic effect of E2-pretreated hUMSCs on inflammation after TBI. After TBI, the retention of hUMSCs in the lungs was higher in the TBI groups than in the Sham groups, and the level of BRG1 in lung was higher in the TBI groups than in the Sham groups; the expression of BRG1 in HUVECs, HPAECs, and hUMSCs treated with TNF-α and LPS were higher than those in the control groups, showing dose- and time-dependent effects. E2 can inhibit the expression of BRG1 and adhesion proteins; after intervention with estrogen receptor inhibitor (ICI 182780) and NF-κ B inhibitor SC75741, BRG1 expression increased and adhesion protein decreased; E2-pretreated MSCs can reduce pulmonary retention, and has no adverse effects on the inflammatory response for TBI. Our study proposes the inflammatory state after TBI leads to enhanced adhesion of blood vessels and transplanted stem cells, which is a contributing factor to the increased aggregation of intravenous hUMSCs in the lungs, E2 can alleviate pulmonary aggregation in stem cell intravenous injection therapy.

Central nervous system (CNS) repair after injury is a challenging process limited by inflammation and neuronal apoptosis. This study identifies Wilms' tumor 1-associating protein (WTAP) as a pivotal regulator of neuronal protection and repair through m6A methylation of STAT3 mRNA. By employing spinal cord injury (SCI) as a representative model of CNS injury, transcriptomic analyses reveal WTAP as a key mediator of pathways related to neuronal autophagy and inflammation regulation. WTAP enhances neuronal autophagy by suppressing STAT3 expression and activity, which inhibits the NLRP3 inflammatory pathway. Functional studies demonstrate that WTAP knockdown exacerbates neuronal apoptosis, whereas overexpression improves cell viability, autophagy, and motor recovery. In vivo, WTAP promotes SCI repair via m6A-mediated suppression of STAT3 and regulation of the NLRP3 signaling pathway, highlighting its therapeutic potential for CNS injury repair.

Glioma is the most common primary brain tumors and has a high recurrence and mortality rate after surgery. Most gliomas are of astrocytic origin. We recently demonstrated that Celsr2 is essential for injury-induced responses and functions of astrocytes, while its role in the development and treatment of gliomas remains unexplored. In this study, an increase of CELSR2 expression was identified in patient glioma samples and glioma cell lines, and higher levels of CELSR2 correlate with poorer patient survival as indicated by TCGA data. In cultured glioma cells, CELSR2 knockdown reduced proliferation and caused cell cycle arrest, which was further supported by proteomic analysis. CELSR2 knockdown inhibited Wnt/β-catenin signaling, and the effect could be reversed by activating β-catenin using GSK-3β inhibitor in glioma cells. WNT3A efficiently enhanced the proliferation of glioma cells and activated the downstream signaling, which were significantly compromised by CELSR2 knockdown. We developed magnetic nanoparticles loaded with CELSR2-siRNA, which suppressed tumor growth in glioma-inoculated nude mice. In conclusion, CELSR2 positively regulates glioma development through WNT3A/β-catenin signaling and inhibiting CESLR2 is a novel therapeutic strategy for gliomas.