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Accurate staging at diagnosis is essential for optimizing treatment strategies and prognosis in early breast cancer (EBC). [ 18 F]FDG positron emission tomography/magnetic resonance imaging (PET/MRI) is a hybrid imaging modality that enables simultaneous evaluation of locoregional disease and metastatic spread. This study assessed the impact of [ 18 F]FDG PET/MRI on treatment planning in patients with EBC. This unplanned sub-study derives from a prospective, interventional, single-arm clinical trial (SNB vs PET/MRI 2) conducted at San Raffaele University Hospital (Milan) between July 2020 and April 2024 (NCT04829643). Patients with EBC scheduled for primary surgery underwent additional preoperative [ 18 F]FDG PET/MRI. The primary objective was the proportion of patients whose treatment strategy was modified following [ 18 F]FDG PET/MRI findings and multidisciplinary discussion. The secondary objective was the performance of [ 18 F]FDG PET/MRI in detecting multifocal breast cancer compared with standard imaging. A total of 264 patients were analyzed. [ 18 F]FDG PET/MRI led to treatment plan modifications 30.7% (81/264, 95% CI: 25.4%-36.5%) of patients. Surgical approach was altered in 23.9% (63/264), while 4.9% (13/264) received primary systemic therapy and 1.9% (5/264) were referred for systemic therapy alone. [ 18 F]FDG PET/MRI showed a sensitivity of 61.7%, specificity of 84.9%, positive predictive value (PPV) of 49.2%, and negative predictive value (NPV) of 90.4% for multifocal disease detection. When combined with standard imaging, PPV increased to 63.6%; sensitivity was 29.8%. [ 18 F]FDG PET/MRI substantially influences treatment decisions in EBC, modifying management in nearly one-third of patients. MRI was highly informative for detecting multifocal disease, whereas the potential added value of [ 18 F]FDG PET/MRI may primarily relate to integrated axillary and distant staging. However, its moderate diagnostic accuracy warrants caution to prevent overtreatment.

To evaluate agreement of proposed CT-based variants with the Vizzielli laparoscopic risk-adjusted score in suspected advanced ovarian cancer and assess inter-reader agreement of CT-derived components. This retrospective single-center study included consecutive adults evaluated between January 2021 and November 2025 for suspected advanced ovarian cancer who underwent contrast-enhanced abdominopelvic CT and staging laparoscopy. Proposed CT-based modifications were operationalized as six score variants combining CT-derived peritoneal tumor burden, CT-estimated ascites, cancer antigen 125 (CA-125), and either Eastern Cooperative Oncology Group performance status (ECOG-PS) or CT-derived body composition parameters. Agreement with the laparoscopic risk-adjusted score was assessed using the intraclass correlation coefficient (ICC), Spearman correlation coefficient, and weighted Cohen's kappa. The final cohort included 80 patients. All CT-based variants showed agreement with the laparoscopic risk-adjusted score. For the variant combining CT-derived PCI, CT-estimated ascites, ECOG-PS, and CA-125, the consistency ICC was 0.76, Spearman's ρ was 0.806, and weighted Cohen's kappa was 0.76. This variant showed 70.0% agreement across the three risk categories and 83.8% agreement for high-risk versus non-high-risk classification, classifying 20 of 22 laparoscopic high-risk patients as high risk. The PCI-based skeletal muscle index (SMI) variant maintained substantial agreement: ICC, 0.73; Spearman correlation coefficient, 0.742; weighted Cohen's kappa, 0.74. Inter-reader agreement was high for CT-derived PCI, with an ICC of 0.91. Proposed CT-based variants showed agreement with the Vizzielli laparoscopic risk-adjusted score. The PCI-based ECOG-PS variant showed the highest agreement metrics, suggesting that structured CT assessment may help approximate laparoscopic risk categories before invasive evaluation.

Recent evidence redefines the Epithelial-Mesenchymal Transition (EMT) from a rigid binary switch into a fluid, multidimensional spectrum. In aggressive breast cancer subtypes, particularly Triple-Negative Breast Cancer (TNBC), this plasticity gives rise to hybrid phenotypes that paradoxically co-express epithelial and mesenchymal traits. These intermediate states fuel collective cell migration and therapeutic evasion by maintaining a balance between cellular adhesion and motility. This review synthesizes current molecular insights into EMT plasticity, focusing on the interconnected regulatory networks involving core transcription factors such as SNAIL, ZEB1/2, and TWIST, alongside upstream signaling pathways like TGF-β and Wnt/β-catenin. Beyond summarizing EMT plasticity and hybrid states, this review specifically bridges the molecular EMT spectrum with the interpretation of common functional migration and invasion assays. We critically evaluate how these molecular states may manifest in functional migration readouts and highlight why migration or invasion outcomes should not be interpreted as standalone evidence of a discrete EMT state. We highlight that migration patterns observed in scratch (wound healing) or transwell assays do not always reflect complete EMT activation, as hybrid cells may exhibit enhanced migratory capacity, including collective migration, compared with fully mesenchymal phenotypes. This necessitates a more integrated approach that combines molecular profiling with functional outcomes to avoid over interpretation of laboratory data. By refining the understanding of metastatic mechanisms, this work aligns with the United Nations' Sustainable Development Goal (SDG) 3 (Good Health and Well-being), specifically contributing to the reduction of premature mortality from non-communicable diseases through improved oncological insights. Such precision in interpreting EMT states is crucial for identifying targetable vulnerabilities and advancing personalized therapeutic strategies in aggressive breast cancer.

Breast cancer represents one of the most frequent causes of morbidity and mortality in Sudan, and late diagnosis, lack of access to specialist care, and socioeconomic factors limit the results of its treatment. Endocrine therapy, which includes the use of tamoxifen, letrozole, and anastrozole, is of vital importance for treating hormone-receptor-positive breast cancer. However, their proper use depends on pharmacists' activities, which should include counselling, ensuring adherence, monitoring adverse effects and interactions, and identifying treatment problems. In the current cross-sectional study, the knowledge, attitude, practice, and barriers of Sudanese pharmacists toward breast cancer pharmacotherapy were studied using a questionnaire survey method. The structured, self-administered online questionnaire was distributed across Sudan. Descriptive and inferential statistical methods were used, including the binary logistic regression, which helped to reveal the independent predictors of good knowledge, favorable attitudes, and practice. The significance level was established to be p < 0.05. A total of 405 Sudanese pharmacists filled out the questionnaire. Most respondents were females (65.9%), aged from 26 to 30 years old (44.0%), had a bachelor's degree in pharmacy (70.9%), and worked in community pharmacies (75.3%). Overall, 52.6% showed good knowledge, 50.1% had a positive attitude, and 50.1% reported good practice concerning tamoxifen, letrozole, and anastrozole. Knowledge was significantly associated with job type (p = 0.002), and practice depended on job type (p = 0.001) and participation in educational programs and workshops (p < 0.001). Also, knowledge was significantly associated with practice (p < 0.001). Multivariable analysis revealed that pharmacists with more than 10 years of work experience had higher odds of good knowledge than those with less than 5 years of experience (OR = 3.095, 95% CI: 1.188-8.064; p = 0.021), while clinical pharmacists had higher odds of good knowledge than those who did not report clinical pharmacy work (OR = 2.827, 95% CI: 1.006-7.942; p = 0.049). No examined factors were significantly associated with positive attitude. Attendance at an educational program was associated with higher odds of good practice (OR = 3.546, 95% CI: 2.240-5.612; p < 0.001). Moderate knowledge and practice in combination with a favorable attitude toward breast cancer endocrine therapy were revealed among Sudanese pharmacists. Job type and education in oncology represent the main predictors of pharmacists' practice, highlighting the need for structured continuing education and stronger pharmacist integration into multidisciplinary cancer care.

To investigate the association between placental morphological abnormalities and adverse pregnancy outcomes in patients with hypertensive disorders of pregnancy (HDP). This retrospective cohort study included patients with HDP who delivered at Wuhan Union Hospital, Wuhan, China, between May 2020 and June 2025. Based on prenatal ultrasound, patients were classified as having abnormal placental morphology (thickened or small placenta) or normal morphology. A two-stage propensity score matching procedure was used to balance baseline characteristics at a 1:2 ratio. Conditional logistic regression stratified by matched pairs evaluated maternal and neonatal outcomes. Model 1 included placental morphology alone, whereas Model 2 additionally adjusted for abnormal umbilical artery or middle cerebral artery Doppler findings and ultrasound-estimated fetal growth lag. Among 1928 patients, 111 (5.8%) had abnormal placental morphology. After matching, abnormal morphology was associated with higher odds of preterm birth, early preterm birth, low birth weight, very low birth weight, 1-minute Apgar score <7, and NICU admission in Model 1. After additional adjustment in Model 2, these associations were attenuated and no longer statistically significant. In subtype analyses, small-placenta subgroups showed more frequent abnormal Doppler findings and suspected fetal growth restriction and generally less favorable neonatal outcomes than the isolated thickening group. Landmark analyses showed that associations detected at 28 weeks included early preterm birth and very low birth weight, with the latter remaining significant after additional adjustment, whereas associations observed at 34 weeks were attenuated after adjustment. Placental morphological abnormalities were associated with adverse pregnancy outcomes in HDP, but these associations were attenuated after accounting for concurrent Doppler and fetal growth abnormalities. Placental morphology may provide complementary structural information as part of integrated assessment of placental and perinatal risk in HDP.

Rheumatic autoimmune diseases induce sustained systemic inflammatory imbalance and substantially elevate the incidence of adverse pregnancy complications, such as recurrent spontaneous abortion, preeclampsia, preterm delivery, and fetal growth restriction. Decidual natural killer (dNK) cells constitute the major lymphocyte subset at the maternal-fetal interface and maintain the homeostasis of immune tolerance, trophoblast invasion and spiral artery remodeling; peripheral NK (pNK) cells differ greatly from dNK cells in phenotype, cytotoxicity and secretory function under the regulation of local uterine microenvironment. Emerging evidence indicates that dysregulated NK‑cell number, subset distribution, receptor signalling and cytokine release may perturb the decidual immune‑vascular microenvironment and contribute to inflammatory placental‑associated pathology, with considerably more robust mechanistic support in antiphospholipid syndrome than in systemic lupus erythematosus, primary Sjögren's syndrome, rheumatoid arthritis, and systemic sclerosis. Solid preclinical and clinical evidence confirms that excessive NK cell activation participates in placental injury in antiphospholipid syndrome, whereas the direct inflammatory pathogenic cascades underlying gestational complications remain insufficiently clarified for other rheumatic disorders. This work elucidates the physiological heterogeneity of pNK and dNK cells, delineates six core inflammatory axes driving NK-mediated placental injury, characterizes disease-specific aberrant inflammatory phenotypes of NK cells, summarizes translational advances in NK-targeted anti-inflammatory strategies, and identifies existing research bottlenecks. We also put forward prospective research schemes based on single-cell multi-omics and large-scale clinical cohorts to reveal NK-centered inflammatory pathology, which offers theoretical support for immune inflammation regulation in childbearing-age women with rheumatic autoimmune diseases.

Accurate assessment of the human epidermal growth factor receptor 2 (HER2) biomarker plays a pivotal role in diagnosing breast malignancies and guiding therapeutic selection, yet routine immunohistochemistry (IHC) testing involves high expenses, requires extensive manual effort, and is subject to diagnostic inconsistencies among pathologists. To overcome these limitations, we propose a cascaded two-stage framework for virtual HER2 IHC synthesis and patch-level classification of HER2 IHC expression from routine hematoxylin and eosin (H&E)-stained images. The prediction target comprises the four conventional HER2 IHC expression categories: 0, 1+, 2+, and 3+. The proposed pipeline operates in two distinct phases. First, a progressive domain knowledge-constrained generative model is developed to synthesize virtual HER2 IHC images from H&E inputs by incorporating structural and staining-aware priors. Second, the generated virtual HER2 images are paired with the corresponding H&E patches and jointly processed by a bimodal fusion network with guided purification and feature recalibration for patch-level classification of HER2 IHC expression. Experiments were conducted on a retrospective breast cancer pathology dataset comprising 48 patients with paired H&E and HER2 IHC whole-slide images (WSIs) digitized at 20x magnification, sourced from patients identified at Xuzhou Central Hospital between January 2018 and December 2023, yielding a total of 9,287 paired patches for model training and testing. The introduced generative framework attains the lowest Fréchet inception distance (FID) of 22.67 among competing methods, indicating superior pathological realism in the synthesized images. In addition, in the four-class patch-level HER2 classification task, the proposed bimodal framework outperforms unimodal H&E-based baselines, yielding an accuracy of 67.12%, an F1-score of 63.63%, and an area under the curve (AUC) of 84.99%. These results demonstrate that the virtual HER2 modality provides complementary HER2-oriented cues beyond native morphology alone and that the proposed framework shows potential as a computational tool for low-cost HER2 assessment from routine H&E images.

Infertility imposes substantial medical, psychological, and financial burdens. Despite recent expansion of insurance coverage for infertility services in Iran, evidence on public willingness to contribute to pooled insurance arrangements remains limited. This study estimated willingness to pay (WTP) for infertility insurance among adults in Kermanshah, western Iran, and identified associated determinants. A cross-sectional contingent valuation study was conducted among 630 adults recruited via convenience sampling in Kermanshah. WTP for a hypothetical package covering 70% of infertility treatment costs (up to two cycles/year) was elicited using a double-bounded dichotomous choice (DBDC) format (bids: 4,000-16,000 thousand IRR). Mean WTP was estimated via maximum-likelihood interval-data regression. Sensitivity analyses evaluated gender composition and response certainty. Of 626 valid respondents, 85.5% expressed positive WTP. Acceptance declined monotonically with increasing bids, supporting construct validity. Mean monthly WTP was 11,107 thousand IRR (95% CI: 10,212-12,003; base) and 11,266 thousand IRR (95% CI: 10,317-12,216; n=451, adjusted). Higher education (β=3,145.56, P=0.011) and socioeconomic status (β=5,254.04, P<0.001) predicted greater WTP; government-funding expectations (β=-5,046.92, P=0.004) and basic insurance (β=-3,697.27, P=0.050) predicted lower WTP. Certainty-calibrated and gender-balanced analyses confirmed robustness. Adults in Kermanshah expressed substantial support for infertility insurance. Given the single-city convenience sample, generalization requires caution. Findings suggest that affordability, socioeconomic gradients, and public expectations regarding government responsibility should be considered in benefit-package and financing design.

The temporal pattern and maternal-offspring burden of pregnancy-associated intracerebral haemorrhage (P-ICH), an uncommon but devastating pregnancy-postpartum complication, have not been comprehensively elucidated. This cohort-crossover study linked four nationwide databases to include pregnancies from 2012 to 2020 in Taiwan. Incidence rate ratios (IRRs) for P-ICH were estimated across six intervals from pregnancy through the full 1-year postpartum, with the corresponding period 730 days prior serving as the control. Cohort-time-control and cohort-cohort-time-control sensitivity analyses were performed to adjust for the 730-day age gap. Maternal-offspring outcomes were compared between pregnancies with and without P-ICH. 406 P-ICH events were identified (crude incidence 19·22 per 100,000 pregnancies). The overall IRR was 1·79 (95% CI 1·52-2·10). The P-ICH risk showed no meaningful difference across pregnancy but peaked during 0-42 days postpartum (IRR 7·44; 95% CI 4·55-12·18), remaining elevated through 43-180 days (IRR 1·58; 95% CI 1·13-2·20) and 181-365 days (IRR 1·38; 95% CI 1·04-1·83) postpartum. Postpartum elevations were sustained meaningfully in sensitivity analyses, except the 181-365-day cohort-time-control estimate. Women with HDP other than chronic hypertension showed a greater P-ICH risk than those without (p interaction = 0·0024). Two-year maternal (12·1% vs 0·1%) and offspring (2·2% vs 0·4%) mortality were substantially higher following P-ICH, with 38·8% of maternal deaths in women developing P-ICH 43-365 days postpartum. P-ICH imposes a substantial and extended postpartum burden, supporting at least 6-month postpartum surveillance and prevention. National Cheng Kung University Hospital.

Bipolar disorder (BD) is associated with risky sexual behavior, however the impact of heredity in this association has not been clarified. We aimed to investigate the association between parental BD and risk of teenage pregnancy and sexually transmitted infection (STI) among their offspring. Data from the Taiwan National Health Insurance Research Database was used for this study. The offspring of parents with BD and matched controls were included. Cox regression analysis was performed to estimate the hazard ratios (HRs) with 95% confidence intervals (CIs) of any STI and teenage pregnancy between the two groups. After adjusting for demographic characteristics and psychiatric comorbidities, the offspring of parents with BD had a significantly higher risk of teenage pregnancy (HR: 1.33; 95% CI, 1.16-1.53) than the matched controls, and a non-significant difference in risk of STI (HR 1.11; 95% CI, 0.93-1.34). The sensitivity analysis showed remained robust HRs after excluding offspring with psychiatric disorders (HR: 1.34; 95% CI: 1.15 to 1.56). We found an association between parental BD and teenage pregnancy among their offspring. Clinicians should be aware of this risk factor in clinical practice.

Endometriosis is a common gynecological disorder characterized by extra-uterine growth of endometrial-like tissues, which causes chronic inflammation, pelvic pain and infertility and greatly impairs patients' quality of life. Despite its high prevalence, the exact pathogenesis of endometriosis remains incompletely understood and clinical therapeutic options are still limited. This paper is a combined narrative-bibliometric review. It systematically summarizes the roles and molecular mechanisms of multiple cellular phenotypic alterations including hypoxic microenvironment, aberrant cell proliferation, dysregulated autophagy, pyroptosis, ferroptosis and epithelial-mesenchymal transition (EMT) in the pathogenesis of endometriosis. Bibliometric analyses were performed based on the Web of Science Core Collection for each sub-theme, with dozens to hundreds of English-language publications included to assist in identifying research hotspots. By integrating evidence from in-vitro cellular experiments, animal models and human tissue studies, this review illustrates the interconnections among these cellular phenotypes, provides theoretical references for understanding the pathophysiology of endometriosis, and discusses corresponding translational and therapeutic implications.

Hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer is driven by an interconnected signaling network centered on estrogen receptor (ER)-dependent transcription. ER signaling interacts bidirectionally with the PI3K-AKT-mTOR pathway and converges with it on the cyclin D-CDK4/6-RB-E2F machinery governing G1-S progression, a circuitry that cyclin E-CDK2 can reinforce or bypass during resistance. This network is now actionable at multiple levels, and recent years have produced an exceptional density of practice-changing innovations. Rather than cataloging individual agents, we interpret these advances as successive efforts to target one interdependent system, organized around three insights. First, ER pharmacology has diversified into mechanistically distinct classes -oral SERDs, PROTAC degraders, complete antagonists (CERANs), covalent antagonists (SERCAs) and modulators (SERMs), joined by KAT6 inhibition- yet the most consistent signal concentrates in the ESR1-mutant setting, a lesson in biomarker-gated development. Second, the principal constraint has been the tolerability ceiling of chronic multi-node blockade; mutant-selective PI3Kα inhibitors and CDK4- and CDK2-selective agents are defined less by new targets than by the selectivity that lifts that ceiling. Third, patient selection is shifting from clinicopathological categories to genomically defined subgroups assessed on tissue and/or circulating tumor DNA (ctDNA), with ctDNA additionally enabling dynamic monitoring and pre-emptive switching in selected scenarios. Synthesizing this landscape, we propose that the contemporary resistance taxonomy can serve as a therapeutic decision roadmap for durable, tolerable, biomarker-guided vertical blockade of the luminal axis.

Women with atrial fibrillation have a higher risk of ischaemic stroke and worse functional outcomes than men but may be less likely to receive adequate anticoagulation. Preliminary single-centre findings in patients treated with endovascular thrombectomy for large vessel occlusion suggest that women may be under-anticoagulated prior to stroke onset. This Stage 1 Registered Report outlines a prespecified analysis plan to test sex-based differences in anticoagulation, stroke characteristics, treatment and outcomes in a prespecified confirmatory population and to explore whether similar patterns are observed at the national level. Using a retrospective cohort design, we will analyse local data from Stavanger University Hospital (2009-22) and national data from the Norwegian Stroke Registry. Confirmatory analyses will include patients with atrial fibrillation and large vessel occlusion treated with endovascular thrombectomy. Sex differences in anticoagulation, stroke severity, treatments and outcomes will be examined using chi-square tests and prespecified regression models; equivalence testing will be applied where appropriate. Exploratory analyses will assess age, comorbidity and healthcare delivery as potential mediators and moderators. No confirmatory analyses have been conducted.

Hypertensive disorders of pregnancy (HDPs) are more common among women with uterine fibroids (UFs), although the role of micronutrients in this association is unclear. We examined associations of nutritional biomarkers with UFs and HDPs in a diverse cohort, and whether these biomarkers modified the association between UFs and HDPs. This cross-sectional secondary analysis of the Boston Birth Cohort included patients with complete UF, HDP, maternal plasma folate and vitamin B12, and cord blood vitamin D data. Biomarkers were analyzed continuously and by quartiles. Logistic regression models evaluated interaction terms and joint exposures. Of 722 participants, 87 (12%) had UFs, and 72 (10%) had HDP(s). Biomarkers did not differ by UF status. Compared with the highest quartile, the lowest folate quartile had higher HDP odds (OR 2.35; 95% CI 1.13-5.12; p for trend = 0.022), as did the highest homocysteine quartile compared with the lowest (OR 2.36, 95% CI 1.07-5.53, p for trend = 0.014). No biomarker × UF interactions were statistically significant. In joint-effects analyses, women with UFs and low folate had higher odds of HDPs than those without UFs and with adequate folate (OR 1.84, 95% CI 1.07-3.17). Co-occurring UFs and low folate were associated with higher HDP odds, without evidence of effect modification. Because maternal blood samples were collected postpartum, we could not determine whether changes in folate levels preceded HDP onset. Prospective studies are needed to determine whether UF and folate status in early pregnancy could inform HDP risk assessment.

Endocrine therapy (ETx) for hormone receptor-positive breast cancer frequently induces menopausal symptoms that may compromise treatment adherence. However, longitudinal symptom trajectories compared with natural menopause remain unclear. This longitudinal study included 5734 women from two prospective cohorts: 2583 women with breast cancer from the Breast Cancer Information Grand Round for Survivorship cohort and 3151 women without breast cancer from the Kangbuk Samsung Health Study. Menopausal symptoms were assessed using the Menopause Rating Scale (MRS). Linear mixed-effects models evaluated longitudinal changes by breast cancer status, menopausal status, and ETx use. Difference-in-differences (DiD) analyses designated premenopausal women without breast cancer as the reference group. Among premenopausal women, ETx was associated with greater increases in total MRS scores than in women without breast cancer (DiD, 3.30; 95% CI, 2.04-4.58 at 1 year). Within the breast cancer cohort, premenopausal women receiving ETx experienced sustained increases in menopausal symptoms over 3 years, with the largest increases observed among those receiving regimens including gonadotropin-releasing hormone agonists. Among postmenopausal women, ETx was associated with modest changes in total MRS scores but a significant increase in urogenital symptoms (DiD 0.71; 95% CI, 0.26-1.16). Compared with women without breast cancer, women receiving ETx experienced greater increases in menopausal symptoms during the first year of follow-up. Within the breast cancer cohort, elevated symptom burden persisted over 3 years, particularly among premenopausal women receiving ovarian function suppression. These findings highlight the importance of proactive symptom monitoring and supportive care during long-term endocrine therapy.

Urosepsis in pregnancy is a life-threatening condition requiring early recognition, rapid multidisciplinary escalation and timely source control. Physiological hydronephrosis is common during pregnancy and may obscure clinically significant urinary tract obstruction. We report a 26-year-old gravida 5 para 3 woman at 30 weeks' gestation who presented with severe right-sided loin pain. Initial ultrasound demonstrated moderate right hydronephrosis without a visible calculus. Within hours, she deteriorated with pyrexia, acute kidney injury, lactic acidosis and septic shock. Computed tomography demonstrated high-grade obstruction of the right renal collecting system secondary to a ureteropelvic junction calculus with associated inflammatory change. Following maternal deterioration and evidence of foetal compromise, an urgent multidisciplinary decision was made to proceed with category 1 caesarean delivery followed by cystoscopy and right ureteric stent insertion. Cultures grew Klebsiella pneumoniae . The patient subsequently required intensive care support including invasive ventilation, vasopressors, renal replacement therapy and treatment for disseminated intravascular coagulation. Both maternal and neonatal outcomes were favourable. This case highlights the diagnostic challenge of distinguishing physiological hydronephrosis from pathological obstruction in pregnancy and emphasises the importance of source control in infected obstructive uropathy.

Postpartum hemorrhage (PPH) is a leading cause of maternal mortality, and women with repeat cesarean sections are at high risk. This study aimed to evaluate the efficacy of prophylactic tranexamic acid (TXA) in preventing PPH among women undergoing repeat cesarean sections. A retrospective cohort study was conducted including women with repeated cesarean sections at a tertiary obstetrical center in South China between July 2016 and December 2023. Patients were divided into the TXA group and the control group according to intraoperative prophylactic TXA administration. Given the imbalance in baseline characteristics, 1:2 propensity score matching (PSM) with a caliper of 0.01 was performed to balance confounding variables. The primary outcome was PPH incidence. Secondary outcomes included estimated blood loss, hemoglobin decline, additional uterotonic use, and blood transfusion rate. After 1:2 PSM, 2,777 women in the TXA group were matched with 5,554 women in the control group, with baseline characteristics well balanced. The incidence of PPH was significantly lower in the TXA group than in the control group (11.09% vs. 17.03%, P < 0.001). The TXA group also demonstrated less calculated estimated blood loss, smaller hemoglobin reduction (12.06% vs. 18.44%, P < 0.001), and lower requirements for additional uterotonic agents (26.90% vs. 29.80%, P = 0.006). Multivariate logistic regression confirmed that prophylactic TXA was an independent protective factor against PPH (OR 0.620, 95% CI 0.540-0.712, P < 0.001). No significant difference was observed in blood transfusion rates (1.55% vs. 2.09%, P = 0.089). Prophylactic TXA use was associated with a lower incidence of PPH and the need for additional uterotonics in women undergoing repeat cesarean sections. Randomized trials in this specific population are needed.

Neutrophil reprogramming toward interferon-activated anti-tumor states represents an emerging mechanism of checkpoint sensitization; however, effective strategies to selectively induce this response in the tumor microenvironment remain elusive. We evaluated Asha Therapy, an investigational non-invasive, low-intensity (50 kHz, 2 mT) alternating magnetic field, in triple-negative breast cancer (TNBC) cells, integrating temporal transcriptomics, global proteomics, and cytokine profiling. CITE-seq profiling of tumor tissue was used to characterize the response of neutrophils and other cell populations in the tumor microenvironment. Therapeutic efficacy of Asha Therapy alone and in combination with anti-PD1 blockade was assessed in a murine TNBC model. A 19-gene neutrophil activation signature was derived from Asha-treated tumors and projected onto three independent human TNBC cohorts (METABRIC, n=348; SCAN-B, n=874; TCGA-BRCA, n=191), with multivariable Cox models adjusted for age, tumor stage, nodal status, and TNBC subtype. Asha Therapy elicited a controlled endoplasmic reticulum (ER) stress response and adaptive unfolded-protein response in TNBC cells. This tumor-intrinsic stress matured from an acute signaling state into an immune-recruiting secretory program characterized by release of CXCL10, CCL2, and CCL20. These signals were associated with selective expansion and activation of neutrophils toward an interferon-responsive state, with additional transcriptional signatures observed within macrophage, T cell, and cancer-associated fibroblast populations. In the murine TNBC model, Asha monotherapy showed directional anti-metastatic effects, while combination with anti-PD1 blockade achieved significant therapeutic benefit, reducing lung metastasis and mortality by 88% (HR=0.12, p<0.05) without overt cytotoxicity. Projection of the 19-gene neutrophil activation signature onto the three human TNBC cohorts revealed significant association with improved overall survival (pooled HR=0.71, 95% CI: 0.60-0.83, p=0.01). These findings indicate neutrophil reprogramming as a key feature of the low-intensity EMF therapeutic response. These preclinical findings support further investigation of Asha Therapy as a candidate non-pharmacologic strategy to activate innate immunity and improve responsiveness to checkpoint blockade in poorly immunogenic tumors.

Breast cancer is the most widespread cancer amongst women worldwide and a major cause of cancer-related death, with the incidence and mortality rates on the rise in sub-Saharan African countries. Another therapeutic axis that has been described but not fully explored in breast cancer treatment is redox homeostasis, which refers to the balance between oxidative load (production of ROS) and antioxidant defences (thioredoxin reductase, glutathione peroxidase and superoxide dismutase); the disruption of this balance can push the cell towards death or sensitise the cell to therapeutic agents. This review mainly covers in silico and experimental findings that explore and focus on metal-based benzimidazole and quinoline complexes as redox-modulating anticancer agents. The functional mechanism of most redox-active complexes (copper, iron and ruthenium) involves direct generation of ROS through Fenton and Haber-Weiss chemistry, and the functional mechanism of most non-redox-active complexes (zinc and platinum) involves coordinative and ligand-substitution mechanisms that disrupt DNA and protein targets, while gold and silver complexes potently inhibit thioredoxin reductase and trigger apoptosis through mitochondrial and Bcl-2-mediated pathways. Molecular docking studies reported for these complexes give favourable calculated docking scores against p53, BAX, BCL-2, PARP, topoisomerase I and DNA, which, in several cases, are more favourable than those for the corresponding free ligands and, in a few cases, cisplatin; these results represent computational predictions and not experimentally determined binding affinities. The drug-likeness, low predicted toxicity and generally good PK profiles agreed with the ADMET and Lipinski assessments, which provide a basis for advancing lead candidates. In summary, the redox properties of metal-benzimidazole and metal-quinoline scaffolds are tunable using ligands, providing a rational multi-target approach to selectively disrupt redox homeostasis in breast cancer, but further in vitro and in vivo validations and clinical translations are required.

Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer accounts for the majority of breast cancers and remains highly dependent on endocrine therapy across both early and advanced disease settings. Although the incorporation of CDK4/6 inhibitors has substantially improved clinical outcomes, endocrine resistance, whether primary or secondary, ultimately limits durable disease control. Resistance arises through heterogeneous and evolving mechanisms, including ESR1 mutations and fusions, ER transcriptional reprogramming, activation of PI3K/AKT/mTOR and other bypass pathways, cell-cycle escape, epigenetic remodeling, and metabolic adaptation. These molecular insights are increasingly being translated into biomarker-guided therapeutic strategies, including next-generation oral selective estrogen receptor degraders, PROTAC ER degraders, and PI3K/AKT/mTOR inhibitors; antibody-drug conjugates are considered separately as antigen-directed options after endocrine resistance. Importantly, circulating tumor DNA monitoring of emerging ESR1 mutations provides an opportunity to identify molecular progression before radiographic progression and to support earlier treatment adaptation. This narrative review integrates recent mechanistic and clinical evidence on endocrine resistance in HR+/HER2- breast cancer, with emphasis on how resistance mechanisms and biomarkers can inform drug selection, treatment sequencing, and dynamic disease monitoring. A mechanism-guided approach may therefore help move clinical management from empiric treatment switching toward more individualized, biomarker-driven, whole-course care.

Migration and forced displacement pose major challenges for sexual and reproductive health (SRH) systems in Latin America. Colombia hosts more than 2.8 million Venezuelan migrants and a large population of internally displaced persons, offering a unique context to examine inequities in maternal health service access and perinatal outcomes. We aim to assess differences in maternal and perinatal outcomes among migrant, forcibly displaced, and non-migrant women in Colombia; explore barriers and facilitators to SRH access from the perspectives of women, healthcare providers, and stakeholders; and analyze how the Colombian healthcare system has adapted to meet the SRH needs of mobile and vulnerable populations. A mixed-methods study with a parallel convergent design was conducted between November 2023 and May 2024 in Bogotá and Cali. Quantitative data from 929 women (250 migrants (26.9%), 134 forcibly displaced women (14.4%), and 545 non-migrants (58.7%) hospitalized for obstetric events were analyzed to compare SRH access and outcomes across migrant, forcibly displaced, and non-migrant groups. Multivariate logistic regressions adjusted for sociodemographic confounders. Qualitative data from 44 semi-structured interviews with women, healthcare providers, and policy stakeholders were analyzed using a multi-framework approach integrating the Tanahashi Coverage Model, Social Determinants of Health, and Complex Systems Theory. Antenatal care utilization and testing rates were similar across groups (mean 5.8 visits, p=0.15). However, maternal mortality occurred exclusively among migrants (400 per 100,000 live births), and perinatal mortality was highest among migrants (37.3/1,000 vs. 18.7/1,000 in non-migrants). Qualitative findings revealed barriers including legal precarity, fragmented insurance, stigma, and limited cultural competence, reducing effective coverage despite nominal access. Although formal service availability appears equitable, structural and sociocultural barriers produce inequitable outcomes for mobile populations. Strengthening SRH equity in Colombia requires adaptive, culturally responsive health policies that integrate social protection, insurance reform, and intercultural training.

Breast cancer cells encounter heterogeneous oxygen conditions arising from abnormal vasculature, impaired perfusion, rapid proliferation, and fluctuating blood flow. Adaptation to oxygen stress is increasingly recognized as a major driver of tumor progression and therapeutic resistance. This review integrates current evidence on the mechanisms through which breast cancer cells adapt to oxygen stress and identifies opportunities for precision therapeutic intervention. Oxygen stress activates hypoxia-inducible factors and interconnected signaling networks that coordinate metabolic reprogramming, mitochondrial adaptation, reactive oxygen species generation, and redox homeostasis. These responses are reinforced by autophagy, unfolded protein response, epithelial-mesenchymal plasticity, cancer stemness, extracellular-matrix remodeling, angiogenesis, and immune suppression. Together, these mechanisms sustain cellular survival, facilitate invasion and metastasis, and promote resistance to chemotherapy, radiotherapy, endocrine therapy, HER2-directed treatment, and other targeted approaches. Oxygen-stress responses vary across breast cancer subtypes, emphasizing the need for biologically informed therapeutic strategies. Potential precision approaches include targeting hypoxia signaling, glycolytic and mitochondrial dependencies, lactate metabolism, antioxidant systems, autophagy, proteostasis, hypoxia-activated pathways, and hypoxia-associated immune suppression. Integrating molecular biomarkers, metabolic profiling, spatial technologies, and functional imaging may improve identification of tumors with actionable oxygen-stress dependencies. Oxygen-stress adaptation represents an interconnected survival network rather than a single hypoxia pathway. Therapeutically exploiting tumor-specific adaptive dependencies, while accounting for subtype and spatial heterogeneity, may provide new opportunities to overcome treatment resistance and improve precision management of breast cancer.

Repeated exposure to heat stress may adversely affect reproductive health, yet the population-level relationship between heat stress and infertility has not been well characterized. We conducted a global ecological analysis across 174 countries and regions from 1990 to 2021. Heat exposure was quantified as the annual number of days falling into four Universal Thermal Climate Index categories: moderate, strong, very strong, and extreme heat stress. We additionally constructed a weighted score combining very strong and extreme heat stress. Associations with male and female infertility prevalence were estimated using linear mixed-effects models. Each additional day of very strong and extreme heat stress was associated with increases in male infertility ASPR of 1.292 (95% confidence interval [CI]: 0.675-1.908) and 1.654 (95% CI: 0.214-3.096) per 100,000 population, respectively. The corresponding increases in female infertility ASPR were 2.126 (95% CI: 0.785-3.467) and 7.133 (95% CI: 3.940-10.323) per 100,000 population, respectively. Higher weighted heat-stress scores were also consistently associated with greater infertility prevalence. These findings suggest that recurrent heat-stress exposure may be associated with a higher population burden of infertility and support consideration of reproductive health in climate-change adaptation and heat-protection strategies.

This infographic summarises the key messages of Frydenberg's et al. (2026) article on the prevalence and impact of pelvic floor symptoms in performing artists and artistic athletes. J Orthop Sports Phys Ther 2026;56(11):750. doi:10.2519/jospt.2026.9004 .

To systematically synthesise and quantify the effects of aerobic exercise on reproductive hormone profiles in women with polyendocrine metabolic ovarian syndrome (PMOS; formerly polycystic ovary syndrome, PCOS), to explore potential moderators, and to provide high-level evidence for precision exercise prescription. This study was prospectively registered in PROSPERO, the international prospective register of systematic reviews (registration number: CRD420251138313). In accordance with the PRISMA guidelines, PubMed, Web of Science, Cochrane Library, Embase, and Scopus were searched from inception to 25 September 2025 to identify randomised controlled trials. Risk of bias was assessed with the Cochrane RoB 2 tool, and the certainty of evidence was evaluated using the GRADE framework. Statistical analyses were performed in R 4.4.3 with the meta and metafor packages for main-effect pooling (Hedges' g ), subgroup and meta-regression analyses, sensitivity analyses, and publication bias assessment. Twenty-five randomized control trials involving 1286 participants were included. Compared with control groups, aerobic exercise reduced testosterone [Hedges' g = -0.45, 95% confidence interval (CI): -0.62 to -0.30; 95% prediction interval (PI): -1.11 to 0.20, P < 0.05], free testosterone (Hedges' g = -0.59, 95% CI: -0.90 to -0.28, 95% PI: -0.99 to -0.19, P < 0.05), the free androgen index (Hedges' g = -0.17, 95% CI: -0.32 to -0.02, 95% PI: -0.32 to -0.02, P = 0.02), dehydroepiandrosterone sulphate (Hedges' g = -0.20, 95% CI: -0.40 to -0.01, 95% PI: -0.43 to 0.02, P = 0.04), and luteinising hormone (Hedges' g = -0.29, 95% CI: -0.53 to -0.05, 95% PI: -1.10 to 0.52, P = 0.02) in women with PMOS, while increasing sex hormone-binding globulin (Hedges' g = 0.17, 95% CI: 0.04 to 0.31, 95% PI: 0.03 to 0.31, P = 0.01) and follicle-stimulating hormone (Hedges' g = 0.26, 95% CI: 0.06 to 0.45, 95% PI: -0.36 to 0.87, P = 0.01). No significant effects were observed on the follicle-stimulating hormone/luteinising hormone ratio (Hedges' g = -0.22, 95% CI: -0.48 to 0.05, 95% PI: -0.56 to 0.13, P = 0.11) or anti-Müllerian hormone (Hedges' g = -0.17, 95% CI: -0.52 to 0.19, 95% PI: -1.12 to 0.78, P = 0.35). Subgroup and meta-regression analyses indicated that younger age was associated with greater improvements in SHBG ( β < 0, P < 0.05); effects on testosterone and the free androgen index were more pronounced in trials with passive control groups than in those with active control groups; intervention duration was negatively associated with changes in FSH ( P = 0.05); and session duration showed a trend towards a positive association with the magnitude of luteinising hormone reduction ( P = 0.06). Aerobic exercise reduces androgen-related markers and luteinising hormone levels and increases sex hormone-binding globulin and follicle-stimulating hormone in women with PMOS, with no significant effects on the follicle-stimulating hormone/luteinising hormone ratio or anti-Müllerian hormone. Age, control type, and exercise modality may moderate intervention effects, and cycling showed potential advantages. However, the number of relevant studies and the sample sizes were limited, and further high-quality randomised controlled trials are needed to confirm these findings. 目的 : 系统整合并量化有氧运动对多内分泌代谢卵巢综合征（PMOS）女性生殖激素谱的效应，探究潜在调节因素，为精准运动处方提供高等级循证依据。 方法 : 基于PRISMA指南，检索 PubMed、Web of Science、Cochrane Library、Embase及Scopus，时间范围为建库起至 2025年9月25日，纳入随机对照试验。采用Cochrane的RoB 2量表评估偏倚风险，并依据GRADE框架判定证据确定性。统计分析在 R 4.4.3 中完成，使用 “ meta ”与“ metafor ” 进行主效应合并（Hedges’ g ）、亚组和元回归分析、敏感性分析及发表偏倚检验。 结果 : 纳入 25 项RCT，共 1286 例。与对照组相比，有氧运动可降低PMOS患者睾酮（Hedges’ g =-0.45，95%CI:-0.62~-0.30，PI:-1.11~0.20， P <0.05）、游离睾酮（Hedges’ g = -0.59，95%CI:-0.90~-0.28，PI:-0.99~-0.19， P <0.05）、FAI（Hedges’ g =-0.17，95%CI:-0.32~-0.02，PI:-0.32~-0.02， P =0.02）、硫酸脱氢表雄酮（Hedges’ g =-0.20，95%CI:-0.40~-0.01，PI:-0.43~0.02， P =0.04）和黄体生成素（Hedges’g=-0.29，95%CI:-0.53~-0.05，PI:-1.10~0.52， P =0.02），同时升高性激素结合球蛋白（Hedges’ g =0.17，95%CI:0.04~0.31，PI:0.03~0.31， P =0.01）和卵泡刺激素（Hedges’g=0.26，95%CI:0.06~0.45，PI:-0.36~0.87， P =0.01）。对卵泡刺激素/黄体生成素比值（Hedges’g=-0.22，95%CI:-0.48~0.05，PI:-0.56~0.13， P =0.11）和抗米勒管激素（Hedges’g=-0.17，95%CI:-0.52~0.19，PI:-1.12~0.78， P =0.35）影响不显著。亚组和元回归分析结果显示:年龄越小与SHBG改善相关（ β < 0， P < 0.05）;被动对照组相较主动对照组效应更明显;训练周期与FSH改变呈负相关（ P = 0.05）;单次训练时长与黄体生成素降低呈正相关趋势（ P = 0.06）。 结论 : 有氧运动可降低PMOS女性雄激素相关指标及黄体生成素水平，升高性激素结合球蛋白和卵泡刺激素，对卵泡刺激素/黄体生成素比值及抗米勒管激素的影响不显著。年龄、对照类型及运动方式可能调节干预效果，骑行显示潜在优势，但相关研究数量和样本量有限，仍需更多高质量随机对照试验验证。本研究已在PROSPERO国际系统综述注册平台完成预注册（注册号:CRD420251138313）。.

Objective: To investigate the clinicopathological features, immunophenotype, and molecular genetic alterations of uterine tumor resembling ovarian sex cord tumor (UTROSCT), and to evaluate its prognostic factors. Methods: Clinical data of 10 UTROSCT cases diagnosed at the Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from January 2019 to November 2025 were reviewed. Hematoxylin and eosin-stained sections were examined. Immunohistochemical staining, fluorescence in situ hybridization (FISH), and RNA sequencing were performed. Follow-up data were obtained and analyzed. Results: The patients' age was 47.50 (33.75, 56.75) years. The predominant clinical manifestation was abnormal uterine bleeding (6/10). Tumors were located in the myometrium (3 cases), endometrial cavity (6 cases), and abdominal cavity (1 case). Histologically, the tumor cells showed mild to moderate atypia, with trabecular, glandular, or solid architectural patterns. Hyaline degeneration was observed in the stroma. All tumors expressed at least 2 sex cord markers (calretinin, α-inhibin, SF-1, and CD56), with various expression of myogenic markers (Desmin and SMA). The Ki-67 proliferation index ranged from 3% to 40% and was≥20% in 2 cases. FISH analyses demonstrated ESR1 rearrangement in 4 cases and GREB1 rearrangement in 6 cases. RNA sequencing identified the gene fusion of GREB1::NCOA1 in 2 cases, GREB1::NCOA2 in 1 case, GREB1::NCOA3 in 1 case, ESR1::NCOA2 in 2 cases, and ESR1::NCOA3 in 2 cases. Two cases showed no detectable fusions due to RNA degradation and insufficient data. Total hysterectomy with bilateral salpingo-oophorectomy was performed in 8 cases, and local excision in 2 cases. Three of the 10 patients received postoperative chemotherapy. The follow-up duration was 2-76 months. Two patients experienced local recurrence at 12 and 16 months after operation, respectively. No distant metastasis was observed in any patient. Conclusions: UTROSCT is a rare low-grade malignant tumor that commonly presents with abnormal uterine bleeding. The immunophenotype is characterized by expression of multiple sex cord and myogenic markers. Its molecular signature is defined by GREB1 or ESR1 fusions with NCOA1/2/3 genes. Patients with the tumor generally follows an indolent clinical course. However, cases with GREB1 rearrangements carry an increased risk of local recurrence. Complete surgical resection is associated with favorable prognosis. 目的： 探讨类似卵巢性索肿瘤的子宫肿瘤（UTROSCT）临床病理特征、免疫表型及分子遗传学改变，并评估其预后相关因素。 方法： 收集郑州大学第一附属医院病理科2019年1月至2025年11月诊断的10例UTROSCT的临床资料，复阅HE染色切片，行免疫组织化学染色、荧光原位杂交（FISH）及RNA测序检测，并随访。 结果： 患者年龄47.50（33.75，56.75）岁；主要症状为异常子宫出血（6/10）。肿瘤位于肌壁间（3例）、宫腔内（6例）、腹腔内（1例）。组织学形态显示肿瘤细胞呈轻至中度异型性，排列方式为梁索状、腺样或实性，间质可见玻璃样变性。免疫组织化学染色显示所有病例均表达至少2种性索标志物（Calretinin、α-抑制素、SF-1、CD56），并不同程度表达肌源性标志物（结蛋白、SMA）。Ki-67阳性指数3%~40%，其中2例≥20%。FISH检测显示4例ESR1断裂、6例GREB1断裂；RNA测序结果显示2例GREB1：：NCOA1融合、1例GREB1：：NCOA2融合、1例GREB1：：NCOA3融合、2例ESR1：：NCOA2融合、2例ESR1：：NCOA3融合，其中2例因RNA降解且数据量不足，未检测出阳性融合。8例行全子宫及双附件切除术，2例行局部切除术；3例患者术后接受化疗。随访2~76个月，2例分别于术后12个月和16个月局部复发，所有病例均未发生远处转移。 结论： UTROSCT是一种罕见的低度恶性肿瘤，常表现为异常子宫出血，免疫表型表达多种性索及肌源性标志物，其分子特征为GREB1或ESR1分别与NCOA1/2/3基因融合。肿瘤整体呈惰性临床经过，但GREB1重排者局部复发风险增加，完整手术切除后预后良好。.

Objective: To evaluate the safety and therapeutic efficacy local flap reconstruction for skin defects following surgery for Stage ⅢB breast cancer. Methods: A retrospective analysis was conducted on 42 patients with Stage ⅢB cancer admitted between January 2018 and December 2023. Among them, 24 patients underwent Auchincloss procedure combined with Stage local flap reconstruction, while 18 patients received neoadjuvant therapy without surgical intervention. Data recorded included operative time, intraoperative blood loss, hospital stay duration, defect reconstruction methods, and flap survival rates. 3-year overall survival rate and local recurrence-free survival rate were observed in both groups. Results: The neoad therapy efficacy rate for both groups was 80.95%(34/42), consisting of a complete response rate of 7.14%(3/42) and a partial response rate of 73.81%(31/42). The follow-up time [ M ( Q 1 , Q 3 )] was 39 (24, 61) months, with a of 5 deaths. Average operative time was 3.1 h (range: 2.5-5.1 h), the mean intraoperative blood loss was 310.0 ml (range: 243.3-392.0 ml), and the mean hospital stay was 11.2 d (range 9.5-17.1 d). The average soft tissue defect area was 13.5 cm×24.2 cm (range 12.0 cm×15.0 cm to 18.0 cm×26.0 cm). Reconstruction methods included direct suturing a modified ZipLine adhesive skin stretcher in 2 cases (8.3%), rectangular flap reconstruction in 6 cases (25.0%), rotation flap reconstruction in 9 cases (37.5%), and latissimus dorsi KISS flap reconstruction in 7 cases (29.2%). Flaps healed in Stage Ⅰ in 23 patients (95.8%); 1 patient (4.2%) experienced flap ischemia, which subsequently healed following intravenous vasodilator therapy. The 3-year overall survival rates for patients in the surgical group and the conservative treatment group were 91.67%(22/24) and 83.33%(15/24), respectively, with no statistically significant difference (log-rank P =0.321); the 3-year local recurrence-free survival for the surgical group and the conservative treatment group were 95.83%(23/24) and 66.67%(12/18), respectively (log-rank P =0.012). Conclusion: The Auchincloss procedure combined with Ⅰ local flap transfer for the repair of massive skin defects following neoadjuvant therapy for Stage ⅢB breast cancer is feasible. 目的： 探讨局部皮瓣修复ⅢB期乳腺癌患者术后皮肤缺损的应用价值。 方法： 回顾性分析2018年1月至2023年12月收治的42例ⅢB期乳腺癌患者的资料，其中24例患者行Auchincloss术联合Ⅰ期局部皮瓣修复术（手术组）；18例患者新辅助治疗后未行手术治疗（保守治疗组）。记录患者手术时间、术中出血量、住院时间、皮肤缺损修复方式和皮瓣成活情况；观察两组患者3年总体生存率和无局部复发生存率。 结果： 患者新辅助治疗有效率为80.95%（34/42），其中完全缓解率为7.14%（3/42），部分缓解率为73.81%（31/42）；随访时间［ M （ Q 1 ， Q 3 ）］为39（24，61）个月，共死亡5例。手术组患者平均手术时间3.1 h（范围2.5~5.1 h），术中平均出血量310.0 ml（范围243.3~392.0 ml），平均住院时间11.2 d（范围9.5~17.1 d）。平均软组织缺损面积为13.5 cm×24.2 cm（范围12.0 cm×15.0 cm~18.0 cm×26.0 cm）。改良式ZipLine粘贴式皮肤牵张器直接缝合2例（8.3%），矩形皮瓣修复6例（25.0%），旋转皮瓣修复9例（37.5%），背阔肌KISS皮瓣修复7例（29.2%）。23例（95.8%）患者皮瓣Ⅰ期愈合；1例（4.2%）患者出现皮瓣缺血，静脉滴注扩血管药物治疗后愈合。手术组与保守治疗组患者3年总生存率分别为91.67%（22/24）和83.33%（15/24），差异无统计学意义（log-rank P =0.321），手术组和保守治疗组3年无局部复发生存率分别为95.83%（23/24）和66.67%（12/18）（log-rank P =0.012）。 结论： ⅢB期乳腺癌新辅助治疗后行Auchincloss术联合Ⅰ期局部皮瓣转移修复巨大皮肤缺损是可行的。.

Epithelial ovarian cancer (EOC) remains the gynecological malignancy with the highest mortality rate. Despite numerous challenges, breakthroughs in its treatment are being achieved at an unprecedented pace. This article focuses on EOC and provides reviews and discussions centered around four current clinical decision-making hot-spots: optimization of initial treatment strategies, breakthroughs in the dilemma of first-line maintenance therapy, re-evaluation of the secondary cytoreductive surgery, and the latest evidence on strategies for platinum-resistant recurrence. By discussing these key issues, we aim to provide a theoretical reference for optimizing clinical strategies and promising avenues for future study, thereby contributing to the continuous advancement of precision and individualized care in the management of epithelial ovarian cancer. Thereby continuously improving the overall precision and individualization of epithelial ovarian cancer management. 上皮性卵巢癌仍是致死率最高的妇科恶性肿瘤，尽管面临诸多挑战，但其诊疗发展正以前所未有的速度不断突破。本文聚焦上皮性卵巢癌，紧扣当前临床决策的四大热点展开系统性述评：初始策略优化选择、一线维持治疗困境突破、二次减瘤手术的价值再评估、铂耐药复发治疗策略的最新证据。通过对上述热点问题的梳理与探讨，该文旨在为临床诊疗路径优化与未来研究方向的确立提供理论参考，从而助力上皮性卵巢癌整体诊疗水平向精准化、个体化的方向持续提升。.

Multimodal general anesthesia (MGA) combines hypnotic adjuvants and regional analgesia, but their individual contributions to postoperative patient-controlled analgesia (PCA) remain unclear. This study evaluated the effects of dexmedetomidine and transversus abdominis plane (TAP) block on PCA-derived analgesic outcomes after uterine surgery. This single-center retrospective propensity-score-matched study included adult women undergoing elective hysterectomy or myomectomy with morphine-based intravenous PCA between 2021 and 2024. Patients were matched 1:1:1 into three groups: MGA with dexmedetomidine plus TAP block, TAP block without dexmedetomidine, and conventional balanced general anesthesia alone. The primary outcome was the 48-h PCA demand/delivery ratio. Secondary outcomes included morphine consumption, pain scores, PCA-related adverse events, and prescription re-adjustment. After matching, 192 patients were analyzed, with 64 patients in each group. The MGA group had the lowest 48-h demand/delivery ratio compared with the TAP-block and control groups (1.00 [1.00-1.13] vs. 1.06 [1.00-1.35] and 1.09 [1.00-1.40], respectively; p = 0.013). Both TAP-containing groups consumed less morphine than controls, whereas morphine consumption did not differ between MGA and TAP block alone. The MGA group had lower intraoperative fentanyl requirement and postoperative-day-1 dynamic pain than controls; neither differed significantly between MGA and TAP-block groups. PCA-related adverse events and re-adjustment rates were comparable among groups. In women receiving morphine PCA after uterine surgery, TAP block was the component most consistently associated with postoperative morphine sparing, whereas dexmedetomidine-containing MGA was associated with a lower PCA demand/delivery ratio without increased adverse events.

Cervical cancer (CC) remains a global health burden. N 6 -methyladenosine (m 6 A) modification regulated by ZC3H13 is critical in carcinogenesis. Collagen triple helix repeat containing 1 (CTHRC1) is dysregulated in multiple malignancies, but the role of the ZC3H13/CTHRC1 axis in the malignant progression of CC stemness and cisplatin sensitivity remains unclear. Bioinformatic analyses, including differential gene screening, weighted gene co-expression network analysis, random forest, least absolute shrinkage and selection operator, and support vector machine recursive feature elimination, were performed on the GSE63514 dataset to identify core genes. SRAMP was used to predict m 6 A sites on CTHRC1 mRNA. Gene expression was detected by quantitative real-time PCR and western blot. Cell proliferation, stemness, apoptosis, and cisplatin sensitivity were assessed by EdU, tumorsphere formation, CD44 flow cytometry, Annexin V-PI staining, and CCK-8 assay, respectively. Regulatory mechanisms were explored by RNA immunoprecipitation (RIP), methylated RIP, and mRNA stability assays, and verified by rescue experiments. Bioinformatic analysis identified CTHRC1 as a core upregulated gene in CC (P = 8.4e-10). CTHRC1 depletion inhibited proliferation, stemness, and promoted cisplatin sensitivity and apoptosis. ZC3H13 was overexpressed in CC (P < 0.001) and positively correlated with CTHRC1 (r = 0.578, P < 0.001). ZC3H13 knockdown decreased CTHRC1 expression and m 6 A enrichment on CTHRC1 mRNA, accompanied by reduced mRNA stability. CTHRC1 overexpression rescued the phenotypes induced by ZC3H13 knockdown. The ZC3H13/CTHRC1 axis modulates CC stemness and cisplatin sensitivity through an m 6 A-dependent mRNA stabilization mechanism, laying a solid molecular foundation for developing novel anti-cervical cancer strategies.