Original research publications

To develop and evaluate machine learning (ML) models to predict clinical pregnancy (CP) outcomes in couples with unexplained infertility (UI) undergoing in vitro fertilization (IVF), thereby enhancing early treatment decision-making and patient counseling. A retrospective analysis was conducted on 145 couples diagnosed with UI and treated at a single-center IVF clinic. Live birth data were not available; therefore, CP was used as the primary outcome. Demographic, clinical, and laboratory parameters were collected, and five ML algorithms-light gradient boosting machine (LGBM), random forest, logistic regression, extra trees classifier, and eXtreme gradient boosting-were applied to predict CP outcomes. Model performance was assessed using the area under the receiver operating characteristic curve (ROC-AUC), accuracy, sensitivity, and specificity. Permutation-based feature importance analysis was performed to identify key predictive variables. Among the evaluated models, the LGBM model achieved the highest test-set ROC-AUC (0.712) and an accuracy of 65.2%. Given the small test sample and the lack of external validation, these findings should be interpreted as exploratory. Variables receiving the highest permutation feature-importance scores included total gonadotropin dose, initial gonadotropin dose, total sperm count, progressive motile sperm count, and infertility duration. These findings should be interpreted as exploratory and do not establish that these variables are independent predictors of CP. This study presents the first ML-based approach tailored to predicting CP outcomes in couples with UI undergoing IVF. The results highlight the potential of artificial intelligence to inform personalized reproductive care. These exploratory findings demonstrate the feasibility of applying ML methods in UI. Larger prospective multicenter studies are required to determine whether clinically useful prediction models can be developed. Açıklanamayan infertilitesi (UI) olan ve in vitro fertilizasyon (IVF) uygulanan çiftlerde klinik gebelik (KG) sonuçlarını öngörmek amacıyla makine öğrenmesi (ML) modelleri geliştirmek ve değerlendirmek; erken tedavi karar verme ve hasta danışmanlığını iyileştirmek. Tek merkezli bir IVF kliniğinde tedavi gören ve UI tanısı alan 145 çift üzerinde retrospektif analiz yapılmıştır. Canlı doğum verileri mevcut olmadığından, birincil sonuç olarak KG kullanılmıştır. Demografik, klinik ve laboratuvar parametreleri toplanmış; KG sonuçlarını tahmin etmek için beş ML algoritması— light gradient boosting machine (LGBM), random forest, lojistik regresyon, extra trees classifier ve eXtreme gradient boosting —uygulanmıştır. Model performansı, alıcı işletim karakteristiği eğrisi altında kalan alan (ROC-AUC), doğruluk, duyarlılık ve özgüllük ile değerlendirilmiştir. Önemli öngörücü değişkenleri belirlemek için permütasyon temelli özellik önem analizi yapılmıştır. Değerlendirilen modeller arasında LGBM, test kümesinde en yüksek gözlemlenen ROC-AUC değerine (0,712) ve %65,2 doğruluğa ulaştı. Küçük test örneklemi ve dış doğrulama bulunmaması nedeniyle bu bulgular keşifsel olarak yorumlanmalıdır. En yüksek permütasyon özellik önem puanlarını alan değişkenler arasında toplam gonadotropin dozu, başlangıç gonadotropin dozu, toplam sperm sayısı, ilerleyici hareketli sperm sayısı ve kısırlık süresi yer almaktadır. Bu bulgular keşifsel olarak yorumlanmalı ve bu değişkenleri klinik gebeliğin bağımsız öngörücüleri olarak belirlememektedir. Bu çalışma, UI’sı olan ve IVF uygulanan çiftlerde KG sonuçlarını tahmin etmeye yönelik ilk ML temelli yaklaşımı sunmaktadır. Bulgular, yapay zekanın kişiselleştirilmiş üreme sağlığı bakımına katkı potansiyelini göstermektedir. Bu ön bulgular, açıklanamayan kısırlıkta makine öğrenme yöntemlerinin uygulanabilirliğini göstermektedir. Klinik olarak faydalı tahmin modellerinin geliştirilip geliştirilemeyeceğini belirlemek için daha büyük, prospektif, çok merkezli çalışmalara ihtiyaç duyulmaktadır.

BackgroundManaging tuberculosis treatment during pregnancy, especially in women with multidrug-resistant tuberculosis (MDR-TB). The World Health Organization recommends a 9-month oral regimen that includes bedaquiline and linezolid, but the effects on pregnancy are not well understood.ObjectiveThis study aimed to assess the impact of a bedaquiline- and linezolid-containing regimen on maternal and fetal health in pregnant women with MDR-TB.MethodsA systematic review was conducted in accordance with the PRISMA guidelines, searching multiple databases for relevant studies published between 2004 and 2025. Study quality was assessed using the Joanna Briggs Institute (JBI) tool.ResultsFour studies were included. The regimen showed favorable treatment outcomes for mothers, with treatment success rates ranging from 60.7% to 98%. However, a high incidence of adverse pregnancy outcomes was reported, including preterm birth (28%-55%), low birth weight (32%-35%), and miscarriage or stillbirth. One study reported a 35% pregnancy termination rate.ConclusionWhile the bedaquiline and linezolid regimen appears highly effective against MDR-TB in mothers, it is associated with significant adverse fetal outcomes. Close monitoring and further research are essential to determine whether the drugs or the underlying MDR-TB disease causes these outcomes.

Golgiphagy contributes to Golgi quality control, yet its regulatory mechanisms and physiological functions remain poorly understood. We identify the deubiquitinase USP28 as an upstream regulator of TM9SF3-dependent Golgiphagy. Nutrient deprivation and Golgi stress induce CRM1-dependent nuclear export of USP28, enabling its translocation to the Golgi, where it removes K48-linked ubiquitin chains from TM9SF3 to prevent its proteasomal degradation and promote Golgiphagy. TM9SF3-dependent Golgiphagy regulates glycosyltransferase abundance through selective degradation of cargo such as MGAT5, thereby maintaining glycosylation homeostasis. Genetic or pharmacological inhibition of the USP28-TM9SF3-Golgiphagy pathway disrupts glycosylation homeostasis and suppresses breast tumor growth. Together, these findings establish the USP28-TM9SF3 axis as a regulatory mechanism linking Golgiphagy to glycosylation homeostasis and breast cancer progression.

Perimenopause is increasingly recognized as a critical period for cardiometabolic health. During the years surrounding the final menstrual period, adverse changes in lipid profiles, insulin sensitivity, body composition and vascular function accelerate beyond those expected from aging alone, concurrent with the emergence and peak severity of menopause symptoms. Accumulating evidence suggests that vasomotor symptoms and sleep disturbance are associated with adverse cardiometabolic profiles and increased cardiovascular disease risk. Mechanistic data indicate that autonomic dysregulation, inflammation and neuroendocrine systems may represent shared pathways linking symptom burden and cardiometabolic dysfunction. Complementing these findings, prospective studies demonstrate that poor cardiovascular health and metabolic dysfunction may predict subsequent symptom development, suggesting that cardiometabolic health influences the menopause transition experience itself. Together, these findings support a model in which perimenopause represents a physiologic convergence point where symptom burden and cardiometabolic risk intersect, with implications for symptom management and primary prevention. However, major evidence gaps remain, including the absence of interventional studies during perimenopause and uncertainty regarding whether these relationships are causal or therapeutically modifiable. Future research should determine whether targeting cardiometabolic health during this window can improve both cardiovascular outcomes and the symptom experience of the menopause transition. Perimenopause is often recognized for symptoms such as hot flashes, night sweats and sleep disturbance, but it is also a time of important changes in cardiovascular and metabolic health. During the years surrounding the final menstrual period, cholesterol levels, insulin resistance, body fat distribution and vascular function can worsen more rapidly than expected from aging alone.Increasing evidence suggests that these changes may be closely connected to menopausal symptoms. Women with more frequent hot flashes and persistent sleep disturbances are more likely to have adverse cardiometabolic profiles and increased cardiovascular risk. At the same time, women with poorer cardiovascular health, higher cholesterol levels, insulin resistance and metabolic dysfunction appear more likely to develop severe vasomotor symptoms. These findings suggest that symptom burden and cardiometabolic health may influence one another through shared biologic pathways involving the nervous system, inflammation and stress-response systems.This review examines how cardiometabolic health changes during perimenopause and explores its relationship with vasomotor symptoms and sleep disturbance. We propose that perimenopause may represent a physiologic convergence point where symptom burden and cardiovascular risk intersect. Importantly, this perspective suggests that improving cardiovascular and metabolic health before and during the menopause transition may have benefits extending beyond long-term disease prevention to potentially improve the menopause experience itself. Understanding these relationships may help identify new opportunities for cardiovascular prevention and symptom management during midlife.

Phosphoglucomutase-1 deficiency (PGM1-CDG) is an ultra-rare, treatable congenital disorder of glycosylation characterized by multisystem involvement. Although galactose supplementation improves biochemical and clinical manifestations, data on pregnancy management and metabolic follow-up in affected women remain extremely limited. We report a woman with genetically confirmed PGM1-CDG who achieved a successful pregnancy with detailed longitudinal metabolic monitoring and maintenance of galactose intake through a lactose-supported diet. The patient was diagnosed during adolescence with a multisystem phenotype including short stature, craniofacial dysmorphism, hepatic involvement, elevated creatine kinase, reduced antithrombin III and left ventricular hypertrophy. She harbored a homozygous PGM1 c.1508G>A (p.Arg503Gln) variant. Long-term pharmaceutical D-galactose supplementation was associated with biochemical improvement, while cardiac involvement remained clinically stable. At 25 years of age, pregnancy was achieved through assisted reproductive technology with her spouse, who was heterozygous for a different PGM1 variant classified as a variant of uncertain significance (VUS). Given the limited safety data on pharmaceutical D-galactose use during pregnancy and uncertainty regarding potential fetal effects, galactose intake was maintained through a lactose-supported diet (estimated galactose intake of approximately 0.5 g/kg/day). Liver enzymes, coagulation parameters and cardiac status remained stable and creatine kinase levels did not worsen. Gestational diabetes was successfully managed with dietary modification alone. No thrombotic, hepatic or cardiac complications occurred. A healthy female infant was delivered by elective cesarean section at 38 weeks. The newborn had a normal metabolic evaluation and was a heterozygous carrier of the maternal PGM1 variant. This case provides detailed longitudinal data on pregnancy in PGM1-CDG and describes the maintenance of dietary galactose intake derived from lactose during a pregnancy with favorable maternal and neonatal outcomes.

Recent observational studies have identified an association between the anxious/worrier trait and endometriosis. However, the causal nature of this relationship remains unclear. Summary statistics from genome-wide association studies were used to identify independent genetic variants associated with the anxious/worrier trait, which served as instrumental variables in a two-sample Mendelian randomization (MR) study. Causal estimates for the effect of emotional factors on endometriosis risk were obtained using inverse variance weighting, MR-Egger regression, and weighted median methods. Reverse MR analysis was then used to assess the impact of endometriosis on emotional indicators. Sensitivity analyses included the MR-Egger intercept test, leave-one-out analysis, and Cochran's Q test, which were used to detect potential pleiotropy and heterogeneity. The inverse variance weighted analysis indicated that the anxious/worrier trait significantly elevated the risk of developing endometriosis (odds ratio 3.84; 95% confidence interval 1.42-10.41, P = 0.008). The results of the reverse MR analysis did not indicate a significant causal effect of endometriosis on emotional indicators (P > 0.05). This study provides genetic evidence for a causal relationship between emotional factors (anxious/worrier trait) and endometriosis. However, the specific biological pathways involved warrant further investigation.

Our objective was to investigate the association between elevated urine protein-to-creatinine ratio (UPCR) and resistant hypertension during postpartum hospitalization in patients with severe preeclampsia at a tertiary care center in Colombia. This retrospective cohort study was conducted in Medellín, Colombia. Patients aged >18 years diagnosed with severe preeclampsia who underwent UPCR assessment were included. Associations between elevated UPCR (≥0.3) and resistant hypertension during postpartum hospitalization were evaluated using robust Poisson regression models. A total of 261 patients were included in the study. Bivariate analysis showed that resistant hypertension in the postpartum period was more frequent in the UPCR ≥0.3 group than in the UPCR <0.3 group (43.2% vs. 12.7%; risk ratio 3.69; 95% confidence interval 1.92-7.07). After adjustment for maternal age, body mass index, and gestational age at diagnosis, elevated UPCR remained independently associated with resistant hypertension (adjusted risk ratio 4.87; 95% confidence interval 1.86-12.76). Earlier gestational age at diagnosis was also independently associated with resistant hypertension. The UPCR is independently associated with the development of resistant hypertension during postpartum hospitalization in patients with severe preeclampsia.

Recent advances in multi-modality treatments (including systemic chemotherapy, endocrine therapy, and radiotherapy) have led to a paradigm shift in the surgical management of breast cancer toward less aggressive approaches. This evolution has established breast-conserving (or breast-reconstructive) surgery as the new standard of care, placing a greater emphasis on aesthetic outcomes. Nipple-sparing mastectomy (NSM) has emerged as an oncologically safe option that is increasingly paired with immediate or delayed breast reconstruction. The NSM approach is also used prophylactically for high-risk individuals with BRCA gene mutations. Compared with traditional total mastectomy, an NSM with breast reconstruction preserves the nipple-areolar complex (NAC), offering significant psychosocial and aesthetic advantages that improve patients' cosmetic appearance and body image. However, some breast cancer patients hesitate to undergo the second stage of breast reconstruction after completing the initial NSM. We conducted a retrospective cohort study using the BREAST-Q questionnaire to assess the postoperative satisfaction and quality of life (QOL) among patients with breast cancer who underwent an NSM with or without subsequent breast reconstruction. We analyzed the cases of 73 patients who underwent breast cancer surgery between December 2016 and December 2022 at a single institution. The cohort was divided into two groups: the breast reconstruction (BR) group (n = 45), that is, the patients who underwent tissue expander or silicone breast implant reconstruction after an NSM, and the non-breast reconstruction (NBR) group (n = 28), comprising patients who underwent an NSM with no intent to pursue subsequent reconstruction. We evaluated and compared the post-NSM overall BREAST-Q scores between the BR and NBR groups. The results revealed no significant difference in overall postoperative satisfaction or QOL between the BR and NBR groups. However, the BR group demonstrated significantly higher scores in the specific domains of psychosocial and sexual well-being, a trend that was particularly pronounced among the patients with small-to-intermediate breast volumes.

Postoperative pain after endometriosis surgery has not been widely investigated, although these patients often present complex pain mechanisms. This study aimed to characterize postoperative pain and analgesic management in patients undergoing intra-abdominal endometriosis surgery at Skåne University Hospital Malmö (Sweden). Background, surgical, anesthetic and intra- and postoperative data were collected from records of patients who underwent intra-abdominal endometriosis surgery between 2021 and 2025. The primary endpoint was the Numeric Rating Scale (NRS) for pain at admission to the Post-Anesthesia Care Unit (PACU). Secondary endpoints included NRS at PACU discharge, opioid use intraoperatively and in the PACU, and the need for pain therapy three weeks postoperatively. Descriptive statistics and regression models were used. Subgroup analyses compared pain in hysterectomy vs. other procedures and the analgesic effect of preemptive spinal analgesia in hysterectomy patients. A total of 155 patient's records were examined. More than half of patients reported an NRS>3 at PACU admission, median value 5 (IQ1-IQ3: 0-7). Median opioid consumption in the PACU was 9 (0-21) mg oral morphine equivalents (OME), while median intraoperative administration was 57 (14-90) OME mg. Fifty percent of the patients still required pain therapy three weeks after surgery and 14 % sought emergency care for abdominal pain not related to surgical complication within a month from discharge. Persistent pain at three weeks was associated with preoperative pain and the need for in-hospital pain service, but not with PACU NRS or opioid use. Hysterectomy patients required more opioids and longer PACU time, and preemptive spinal analgesia was associated with less need for pain therapy at three weeks after hysterectomy. Persistent postoperative pain is common after endometriosis surgery. Preoperative pain history and the involvement of a pain specialist during admission predicted persistent pain at three weeks after surgery better than PACU pain intensity alone.

Preeclampsia (PE) is a leading cause of maternal morbidity, linked to systemic inflammation and nutritional imbalance. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score, an immune-nutritional index, was assessed in PE. A retrospective case-control study included non-pregnant healthy women (NonP), healthy pregnant women (HP), and women with PE. HALP was calculated and compared across groups. Correlations, principal component analysis (PCA), regression, and ROC analysis were performed. HALP was significantly lower in PE than HP and NonP (p < 0.001), with the steepest decline in women >36 years. HALP correlated positively with lymphocytes, albumin, and hemoglobin, but negatively with neutrophils and WBCs. PCA highlighted albumin and lymphocytes, while regression identified WBCs as an independent predictor. ROC analysis showed good discrimination for NonP vs PE (AUC = 0.764). HALP is reduced in PE and may serve as a simple, accessible biomarker for risk stratification. La prééclampsie (PE) est une cause majeure de morbidité maternelle, associée à une inflammation systémique et à un déséquilibre nutritionnel. Le score HALP (hémoglobine, albumine, lymphocytes et plaquettes) — un indice immuno-nutritionnel — a été évalué dans le contexte de la PE. Une étude cas-témoins rétrospective a inclus des femmes non enceintes en bonne santé (groupe NonP), des femmes enceintes en bonne santé (groupe HP) et des femmes atteintes de PE. Le score HALP a été calculé et comparé entre les groupes. Des analyses de corrélation, une analyse en composantes principales (ACP), des analyses de régression et une analyse par courbe ROC ont été réalisées. Le score HALP était significativement plus faible chez les femmes atteintes de PE que chez celles des groupes HP et NonP (p < 0,001), la baisse la plus marquée étant observée chez les femmes de plus de 36 ans. Le score HALP présentait une corrélation positive avec les lymphocytes, l'albumine et l'hémoglobine, mais une corrélation négative avec les neutrophiles et les globules blancs. L'ACP a mis en évidence le rôle de l'albumine et des lymphocytes, tandis que l'analyse de régression a identifié les globules blancs comme un facteur prédictif indépendant. L'analyse par courbe ROC a montré une bonne capacité de discrimination entre les groupes NonP et PE (AUC = 0,764). Le score HALP est diminué en cas de PE et pourrait constituer un biomarqueur simple et accessible pour la stratification du risque.

Cervical cancer remains a major public health concern in sub-Saharan Africa, particularly in Namibia, where high rates of HIV and HPV infections and early sexual activity increase its prevalence. Limited awareness of cervical cancer among Namibian women contributes significantly to delayed screening and treatment, reducing the likelihood of successful outcomes. This qualitative study explored the perceptions and experiences of 73 professional nurses purposively selected from public primary healthcare facilities across Namibia's fourteen regions. Data were collected through focus group discussions and analysed thematically, with an independent coder to ensure rigor. Findings revealed a substantial lack of awareness among women, highlighting the need for nurses to lead educational initiatives. The study advocates empowering nurses to strengthen patient-nurse relationships and implement community-based awareness programs, including media outreach to isolated populations. It contributes to public health knowledge by emphasizing strategies to promote prevention, early diagnosis, and improved cervical cancer outcomes in Namibia. Le cancer du col de l'utérus demeure un problème majeur de santé publique en Afrique subsaharienne, notamment en Namibie, où les taux élevés d'infections par le VIH et le VPH ainsi que la précocité des rapports sexuels contribuent à son ampleur. Le manque de connaissances sur le cancer du col de l'utérus chez les Namibiennes retarde considérablement le dépistage et le traitement, réduisant ainsi les chances de guérison. Cette étude qualitative a exploré les perceptions et les expériences de 73 infirmières professionnelles sélectionnées de manière ciblée dans des établissements de soins de santé primaires publics répartis dans les quatorze régions de Namibie. Les données ont été recueillies par le biais de discussions de groupe et analysées thématiquement, avec un codeur indépendant afin d'en garantir la rigueur. Les résultats ont révélé un manque important de connaissances chez les femmes, soulignant la nécessité pour les infirmières de mener des initiatives éducatives. L'étude préconise de donner aux infirmières les moyens de renforcer la relation soignant-patient et de mettre en œuvre des programmes de sensibilisation communautaires, notamment par le biais de campagnes médiatiques auprès des populations isolées. Elle contribue à l'avancement des connaissances en santé publique en mettant l'accent sur les stratégies visant à promouvoir la prévention, le diagnostic précoce et l'amélioration des résultats en matière de cancer du col de l'utérus en Namibie.

The integration of anthracyclines with HER2-targeted agents in neoadjuvant therapy for HER2-positive breast cancer has been limited by cardiotoxicity concerns. This randomized phase II METIS trial (NCT04172259) assessed whether concurrent pegylated liposomal doxorubicin (PLD)-containing chemotherapy plus dual HER2 blockade (trastuzumab/pertuzumab) could improve efficacy without increasing cardiac risk. A total of 156 patients with stage II-III HER2-positive breast cancer were randomized to a PLD-based concurrent regimen or an epirubicin and cyclophosphamide (EC)-based sequential regimen. The PLD-based concurrent group achieved a higher pathological complete response (pCR) rate (67.5% vs. 48.7%; difference, 18.8%; 95% confidence interval [CI], 3.6-34.0; P = 0.033) compared with the EC-based sequential group, with greater benefit in hormone receptor-positive disease (58.7% vs. 36.7%) and stage II tumors (82.1% vs. 48.0%). After a median follow-up of 37.5 months, fewer event-free survival (EFS) events occurred in the PLD-based concurrent group (3 vs. 8), yielding a hazard ratio (HR) of 0.35 (95% CI, 0.09-1.32; P = 0.105). The estimated 3-year EFS rates were 96.0% (95% CI, 88.1-98.7) versus 90.7% (95% CI, 81.5-95.6). Achieving pCR was significantly associated with improved EFS (HR = 0.15; 95% CI, 0.03-0.71; P = 0.006). Cardiac safety was comparable, with no symptomatic cardiac dysfunction and only one grade ≥3 cardiotoxicity in the EC-based sequential group. These findings support PLD-based concurrent therapy with trastuzumab and pertuzumab as an effective and safe neoadjuvant option for high-risk HER2-positive breast cancer, warranting further evaluation in phase III trials.

Fertility-sparing surgery for early-stage cervical cancer aims to preserve reproductive potential without compromising oncologic outcomes. Post-operative surveillance must balance 3 priorities: early detection of treatable recurrence, detection, and management of premalignant disease in the residual cervix or upper vagina, and avoidance of low-yield tests that trigger additional procedures, cancer-related distress, and potentially detrimental effects on fertility. This narrative review summarizes the best available evidence on follow-up after fertility-sparing surgery for human papillomavirus-related cervical cancer, with specific attention to the comparative value of human papillomavirus testing versus symptom review, pelvic examination, colposcopy, and cervical cytology. Key findings include: (1) Many clinically relevant central recurrences occur early, although extra-cervical relapse remains important in higher-risk cohorts, supporting careful clinical follow-up in the first post-operative years; (2) Cervical cytology after trachelectomy frequently yields abnormalities that rarely change management, highlighting the importance of confirmatory colposcopy; and (3) Combining human papillomavirus status and cytology results stratifies risk for subsequent recurrent cervical intra-epithelial neoplasia grade 2 or worse, suggesting a role for risk-adapted surveillance intervals. Currently, evidence does not support indiscriminate routine human papillomavirus testing for all patients after fertility-sparing surgery as a standalone strategy to detect invasive recurrence. However, selective use in combination with cytology and colposcopy, particularly to tailor visit frequency in patients with reassuring results after the first year, is supported by emerging evidence and is consistent with contemporary guidance. Any implementation should define management pathways for positive tests and account for the low pre-test probability of recurrence in many patients, so that harms from false positives do not outweigh benefits.

ObjectiveTo investigate whether early-pregnancy insulin resistance in women with polycystic ovary syndrome (PCOS) is associated with adverse maternal pregnancy complications and neonatal/perinatal outcomes after adjustment for common metabolic confounders.MethodsThis retrospective cohort study included 168 pregnant women diagnosed with PCOS who were consecutively enrolled at Tongren Hospital from July 2023 to December 2024. Of these, 52 patients with insulin resistance (homeostasis model assessment of insulin resistance ≥ 2.77) were assigned to the PCOS with insulin resistance group, whereas 116 patients without insulin resistance were assigned to the PCOS without insulin resistance group. Multivariable binary logistic regression was performed to estimate adjusted associations between insulin resistance and gestational diabetes mellitus, adjusting for age, body mass index, family history of diabetes, and conception mode.ResultsBody mass index was significantly higher in the PCOS with insulin resistance group ( p = 0.02). No significant differences were found in thyroid function indices or blood lipid levels across trimesters, neonatal birth weight, or perinatal outcomes (all p > 0.05). The incidence of gestational diabetes mellitus was higher in the PCOS with insulin resistance group than in the PCOS without insulin resistance group (30.77% vs. 17.24%, p = 0.04). After adjustment for potential confounders, insulin resistance (adjusted odds ratio = 2.09, 95% confidence interval: 1.02-4.28, p = 0.044) and higher body mass index (odds ratio = 1.19 per kg/m 2 , p = 0.038) remained independently associated with increased odds of gestational diabetes mellitus. No significant differences were observed in gestational hypertension, polyhydramnios, or premature rupture of membranes.ConclusionsIn this observational cohort, early-pregnancy insulin resistance was associated with a higher incidence of gestational diabetes mellitus after adjustment for body mass index and other confounders. These findings do not establish a causal relationship. Early standardized screening and targeted metabolic management of insulin resistance may help reduce gestational diabetes mellitus incidence; however, prospective studies are warranted to confirm this association.

The transition into the postpartum period brings deep physical, emotional, and relational shifts, placing individuals at a significant risk for both pelvic floor dysfunction (PFD) and perinatal mood and anxiety disorders (PMADs). Despite their prevalence, symptoms of both PFD and PMADs are frequently overlooked during routine postpartum follow-up visits, ultimately compromising maternal role performance, daily functioning, and family well-being. Home-based health practitioners (HHPs) can address these gaps during home visits by applying trauma-informed assessment strategies, using brief validated screening tools, and establishing a safe environment for open discussion. This article defines the intersection of PFD and PMADs, describes a methodology for evidence-based home intervention, and provides practical strategies to enhance functional postpartum recovery in the home setting.

Wernicke's encephalopathy (WE) is a rare, acute neurological condition that develops due to thiamine deficiency in pregnant women with severe hyperemesis gravidarum (HG). This is a case report of a 28-year-old woman at 17 weeks of gestation with a prior spontaneous abortion and a history of laparotomy surgery to treat infertility. The patient had three out of four diagnostic requirements as put by the European Federation of Neurological Societies. Brain magnetic resonance imaging (MRI) showed symmetrical medial thalamic hyperintensities consistent with WE. Notably, thyroid function tests revealed gestational thyrotoxicosis, which contributed to HG severity but did not explain the cerebellar dysfunction or characteristic MRI changes, indicating superimposed thiamine deficiency and coexistence of HG-related thyrotoxicosis and WE. WE is significantly underdiagnosed in the nonalcoholic population, especially in pregnant women who generally have a high demand for thiamine. This case highlights the need to consider WE in pregnant women presenting with prolonged HG and to initiate parenteral thiamine promptly to prevent irreversible neurological injury.

The rising prevalence of reproductive disorders, including male infertility, necessitates innovative therapeutic strategies. Plant-based extracts, particularly those from Chrysopogon zizanioides (vetiver plant), have emerged as promising candidates. This study employs in silico methodologies to evaluate the therapeutic potential of vetiver-derived compounds against male infertility. This research aims to investigate the pharmacokinetic profiles, bioactivity, toxicity, and molecular interactions of vetiver compounds with proteins implicated in male reproductive health. The study integrates Absorption, Distribution, Metabolism, and Excretion (ADME) predictions, protein-protein interaction (PPI) analysis, bioactivity and toxicity evaluations, and molecular docking and simulation studies to assess therapeutic viability. ADME tools analyzed the pharmacokinetic profiles of vetiver compounds. Network pharmacology approaches and PPI analysis mapped interactions with target proteins. Bioactivity and toxicity assessments ensured compound safety and efficacy. Molecular docking and simulations examined the binding affinities and dynamic interactions of selected compounds with target proteins. Out of 120 screened compounds, phenolic derivatives were prioritized. Channaine (Ligand-4) exhibited strong therapeutic potential, with 91.2% intestinal absorption, favorable tissue distribution (Vdss: 1.214 log L/kg), and low toxicity (lethal dose 50%: 2.953 mol/kg). Docking revealed strong binding affinities with Nuclear Factor Erythroid 2-Related Factor 2 (NFE2 L2) (-7.4 kcal/mol), Krüppel-like factor (KLF5) (-4.4 kcal/mol), and Nuclear Factor Kappa B Subunit 1 (NFKB 1) (-7.0 kcal/mol). Simulations confirmed stable protein-ligand interactions, supporting its therapeutic promise. Vetiver extracts show significant potential for treating male infertility, offering favorable pharmacokinetics, low toxicity, and effective target interactions. These findings warrant further experimental and clinical validation.

Pregnancy-associated venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality. Pregnancies achieved by in vitro fertilization carry an increased risk of VTE, particularly during early gestation. A 33-year-old woman developed deep vein thrombosis during late pregnancy in her first spontaneous conception despite no identifiable thrombophilia. During a subsequent pregnancy achieved by natural cycle frozen embryo transfer, which was selected to avoid exogenous estrogen exposure and potentially reduce the thrombotic risk compared with hormone replacement cycles, she developed recurrent VTE at 8 weeks of gestation. Anticoagulation therapy was initiated, and an inferior vena cava (IVC) filter was placed in late pregnancy because of persistent thrombus and delivery-related risk. A cesarean section was successfully performed, and the IVC filter was removed postpartum after regression of the thrombus. Although natural cycle frozen embryo transfer may reduce the thrombotic risk compared with hormone replacement cycles, it does not eliminate the risk of recurrent VTE in women with a history of pregnancy-associated thrombosis. Early initiation of anticoagulation and careful peripartum management, including selective use of IVC filters, are essential in high-risk patients.

Ovarian cancer (OC) remains the most lethal gynaecological malignancy, and acquired resistance to PARP inhibitors such as olaparib represents a major clinical challenge. Although dysregulation of iron metabolism has been implicated in tumorigenesis, the specific role of the iron exporter SLC40A1 (ferroportin, FPN) in mediating olaparib resistance remains poorly understood. The study aimed to elucidate the clinical significance of FPN deficiency and to explore therapeutic strategies for reversing olaparib resistance. FPN expression was evaluated in OC samples from a clinical cohort of 19 patients, stratified by olaparib responsiveness, to determine its prognostic value. Functional mechanisms were investigated using multiple OC cell lines, patient-derived organoids (PDOs), and mouse xenograft models. We integrated analyses of iron homeostasis, ROS dynamics, DNA repair capacity, and innate immune signaling, with a focus on the cGAS-STING-STAT3 signaling cascade. The therapeutic potential of combining olaparib with the ferroptosis inducer erastin or the STING inhibitor C-176 was assessed as a strategy to overcome FPN deficiency-driven resistance. Clinically, FPN expression was significantly downregulated in olaparib-resistant tissues compared with sensitive controls (p < 0.05), and low FPN levels were strongly associated with poor therapeutic outcomes. Mechanistically, FPN deficiency promoted intracellular iron accumulation and ROS generation, which led to increased ferroptosis vulnerability, impaired homologous recombination repair (HRR) and concomitant activation of the cGAS-STING-STAT3 inflammatory axis, thereby driving olaparib resistance. Notably, in vivo studies demonstrated that combining olaparib with either erastin or C-176 significantly suppressed tumour growth and restored drug sensitivity compared with monotherapy (p < 0.01), supporting the translational potential of targeting this axis. Our study establishes a clinically relevant mechanistic connection between ferroportin deficiency and cGAS-STING-STAT3-mediated olaparib resistance in OC. We identify the FPN-ROS-cGAS-STING-STAT3 axis as an actionable vulnerability in resistant OC, indicating that this pathway is a promising therapeutic target to overcome olaparib resistance. FPN loss drives olaparib resistance and predicts poor outcomes in ovarian cancer. FPN loss causes iron and ROS accumulation, impairing HRR and activating the cGAS-STING-STAT3 axis. The cGAS-STING-STAT3 pro-survival program drives olaparib resistance. STING inhibition restores olaparib sensitivity in resistant ovarian cancer.

Cervical cancer (CC) remains a major global health challenge characterized by high incidence and mortality. The histone methyltransferase suppressor of variegation 3-9 homolog 1 (SUV39H1) has emerged as a key epigenetic regulator in tumor progression, but its role in modulating pyroptosis and remodeling of the immune microenvironment in CC remains unclear. In this study, we demonstrate that SUV39H1 promotes CC progression through dual epigenetic regulation, specifically repression of gasdermin E (GSDME) and activation of chemokine (C-X-C motif) ligand 10 (CXCL10). Overexpression of SUV39H1 in HeLa and SiHa cells enhanced histone 3 lysine 9 tri methylation (H3K9me3) deposition at the DFNA5 (GSDME) promoter, resulting in reduced transcription and suppressed GSDME-dependent pyroptosis-like cell death. Interestingly, it also upregulated CXCL10 expression. Functional assays confirmed that SUV39H1 attenuated GSDME-mediated pyroptosis-like cell death and enhanced cell migration via induction of epithelial-mesenchymal transition (EMT). Moreover, SUV39H1 drives CXCL10 secretion, which activates the chemokine (C-X-C motif) receptor 3 (CXCR3) signaling axis in macrophages and upregulates immunosuppressive molecules including programmed death ligand 1 (PD-L1), T cell immunoglobulin and mucin-domain containing-3 (Tim-3), and secreted phosphoprotein 1 (SPP1), thereby fostering an immunosuppressive tumor microenvironment (TME), and these effects appear parallel to GSDME suppression. Collectively, these findings reveal a multifaceted oncogenic role of SUV39H1 in CC, highlighting its potential as a therapeutic target for epigenetic and immunomodulatory intervention.

To characterize medication-related Knowledge-Attitude-Practice (KAP) risk profiles, pregnancy- and lactation-specific medication familiarity, and demographic correlates among pregnant and postpartum women in Taiyuan, China. We conducted a hospital-based cross-sectional survey at Taiyuan Taihang Hospital from July to October 2024 using convenience sampling and an adapted medication-related KAP questionnaire. Higher knowledge-, attitude-, and behavior-risk scores indicated less favorable profiles, whereas higher familiarity scores indicated greater self-rated familiarity. Internal consistency was assessed using Cronbach's α. Associations were examined using Pearson correlations, Welch's analysis of variance with Games-Howell post hoc tests, and multivariable ordinary least-squares regression with HC3 robust standard errors. Of 500 returned questionnaires, 497 were analyzed. Cronbach's α ranged from 0.808 to 0.957. Mean knowledge-risk and behavior-risk scores were 59.78 ± 18.99 and 57.22 ± 11.29, respectively, both within the prespecified good category; the mean attitude-risk score was 37.34 ± 7.94, within the pass category. For attitude risk, 59.0% were classified as pass, 16.1% as fail, and 24.9% as good or excellent. Knowledge risk was inversely correlated with attitude risk ( r = -0.258) and positively correlated with behavior risk ( r = 0.275), while attitude risk was weakly positively correlated with behavior risk ( r = 0.118; all p ≤ 0.009). In the adjusted behavior-risk model, higher scores were observed among participants aged 35-49 years and those with other insurance or self-payment. The overall adjusted association between monthly income and behavior risk was not statistically significant (Wald p = 0.098); an isolated contrast between the 4,000-6,000-yuan and below-2,000-yuan groups reached nominal statistical significance and was treated as exploratory. Familiarity scores across five pregnancy- and lactation-specific topics ranged from 2.46 to 2.60 on a five-point scale. Favorable knowledge- and behavior-risk profiles coexisted with less favorable attitude-risk classifications and limited topic-specific familiarity. Broad medication-safety counseling should be integrated into antenatal and postpartum care, with proactive medication review considered for women aged 35-49 years, those with other insurance or self-payment, and those with complex medication needs. The income finding should be regarded as exploratory. Multicenter prospective studies are needed to assess generalizability and evaluate this service approach.

Fusobacterium nucleatum , an oral-associated bacterium implicated in several extraoral diseases, has recently been proposed as a potential contributor to endometriosis through microbial translocation, inflammation, and fibrosis. However, the consistency and clinical significance of this association remain uncertain. This systematic review evaluated the human and experimental evidence linking F. nucleatum with endometriosis and assessed the plausibility of a proposed oral microbe-host axis. PubMed/MEDLINE, Embase, Web of Science, and Google Scholar were searched from inception through August 31, 2026, following PRISMA 2020 guidelines. Human and animal studies reporting F. nucleatum or historically related F. nucleatum -complex taxa in relation to endometriosis were included. Risk of bias was assessed using a prespecified adapted ROBINS-I framework for human observational studies and SYRCLE for animal studies. Owing to substantial heterogeneity in anatomical compartments, detection methods, and outcomes, meta-analysis was not appropriate and findings were synthesized qualitatively. Four human studies encompassing 384 participants at the study level were included, although analysis-specific denominators varied. Direct tissue evidence came from two studies and was conflicting: Muraoka et al. reported Fusobacterium positivity in 64.3% of endometrial samples from women with endometriosis versus 7.1% of controls in a 42-versus-42 tissue subset, whereas Graciano-España et al. found no significant case-control difference in F. nucleatum abundance among 55 cases and 37 controls. Indirect microbiome studies reported oral Fusobacterium enrichment in moderate/severe endometriosis and vaginal F. animalis depletion in chronic pelvic pain with endometriosis. All human studies were judged at serious overall risk of bias, and certainty of evidence was very low. Experimental evidence suggesting TGF-β-mediated lesion growth and fibrosis derived principally from one translational study and lacked independent replication. Current evidence supports biological plausibility but not a consistent or causal association between F. nucleatum and endometriosis. Direct tissue evidence is limited to two conflicting studies, while non-tissue microbiome findings are indirect. Standardized contamination-controlled sampling, paired anatomical-site sampling, strain-level analyses, and longitudinal studies are required before microbial translocation, temporality, causality, or antimicrobial treatment can be established. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261337885.

Vaginal laxity (VL) is a prevalent condition affecting women's quality of life, characterized by reduced vaginal tightness, sexual function impairment, and psychological distress. While surgical vaginoplasty and energy-based devices (radiofrequency and laser) are commonly used, these approaches have important limitations, including surgical risks, variable durability, and limited evidence quality. Collagen dysregulation is increasingly recognized as a key pathophysiological feature of VL, and collagen-based biomaterials have emerged as potential regenerative interventions. However, the evidence specifically linking collagen fiber biology to VL remains scattered, and a systematic synthesis of recombinant humanized type III collagen (rhCol III) for this indication is lacking. This narrative review systematically summarizes current evidence on the pathophysiological role of collagen in VL, the material properties and mechanisms of action of rhCol III freeze-dried fibers, and the available preclinical and clinical data for this intervention, with consideration of its potential relevance to the broader spectrum of pelvic floor dysfunction. Recombinant humanized type III collagen freeze-dried fibers exhibit good biocompatibility and biodegradability due to their structural homology with native human collagen. Their proposed mechanism of action involves three complementary pathways-physical support and structural filling, biochemical regeneration via upregulation of endogenous collagen synthesis, and microenvironment modulation including angiogenesis and anti-inflammatory effects-although several specific molecular pathways have been characterized primarily in non-vaginal tissue models and require direct validation in vaginal tissue. Available clinical evidence from a single small two-center randomized controlled trial ( n = 84) demonstrates significant short-term improvements in VL symptoms and sexual function at 4 weeks, with a favorable short-term safety profile. However, the evidence base remains early-stage, with no large-scale multicenter trials, no long-term follow-up data, and no head-to-head comparisons with established treatments. rhCol III freeze-dried fibers represent an emerging, biologically plausible intervention for VL that warrants further investigation. Key knowledge gaps include the need for large-scale randomized trials with long-term efficacy and safety data, standardized treatment protocols, comparative effectiveness studies, and direct mechanistic validation in vaginal tissue. The potential applicability to other pelvic floor disorders remains speculative at this stage.

Platinum-based chemotherapy plus cytoreductive surgery represents the standard first-line therapy for ovarian cancer (OC), which yields robust early therapeutic responses in most patients. However, platinum resistance is a formidable clinical hurdle, and how macrophages mediate drug resistance within the OC tumor microenvironment remains poorly understood. We cultured SKOV3 OC cells and THP-1 monocytes, induced THP-1 differentiation into M2d tumor-associated macrophages. Stable apolipoprotein E (ApoE) -overexpressing SKOV3 cell lines were constructed via lentiviral transfection and puromycin screening. We established nude mouse subcutaneous xenograft models with mixed tumor cells and M2d macrophages, administered cisplatin treatment and collected tumor tissues after sacrifice by cervical dislocation. RNA was extracted from tumor samples to conduct RT-qPCR for gene expression detection. Tumor tissue sections were prepared for HE staining, TUNEL apoptosis staining, and Western blot analysis to detect ApoE and phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway protein expression. Using nude mouse subcutaneous xenograft models, we demonstrated that M2d-type tumor-associated macrophages (M2d TAMs) promote platinum resistance and elevate tumoral ApoE levels. In OC xenografts with stable ApoE overexpression, cisplatin-induced apoptosis was profoundly repressed, resulting in reduced cisplatin sensitivity, while this inhibitory effect was not observed in the empty vector control group. Mechanistically, ApoE activates the PI3K/AKT/mTOR signaling cascade to counteract cisplatin cytotoxicity by suppressing cell death and sustaining pro-survival signals. Overall, this study reveals that M2d TAMs induce platinum resistance in OC cells via exosomes carrying ApoE.

This Viewpoint discusses how the One Big Beautiful Bill Act (HR 1) will undermine maternal health by disrupting preconception coverage and care, reducing access to family planning services, and introducing administrative complexity that exposes pregnant women to erroneous disenrollment.

Treatment-resistant breast cancer remains a major clinical challenge because conventional clinicopathological and molecular biomarkers incompletely capture the dynamic interactions between tumour cells, immunity, inflammation, and the systemic host response. Next-generation inflammatory signatures offer an opportunity to expand the diagnostic-prognostic landscape by integrating cellular, molecular, immune, and thromboinflammatory indicators with established tumour characteristics. This narrative review critically examines emerging evidence for neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index, C-reactive protein, cytokines, tumour-associated macrophages, myeloid-derived suppressor cells, neutrophil extracellular traps, coagulation biomarkers, and liquid-biopsy-derived measures in treatment-resistant breast cancer. Particular attention is given to sources of heterogeneity, including population characteristics, tumour subtype, treatment exposure, comorbid inflammation, sampling time, specimen processing, analytical platforms, and inconsistent biomarker thresholds. The review further evaluates the transition from biomarker discovery to clinical decision support, highlighting the need for prospective multicentre validation, standardised analytical procedures, external validation of computational models, and integration with molecular subtyping, circulating tumour DNA, imaging, and immune profiling. Rather than interpreting inflammation as a static prognostic variable, longitudinal inflammatory trajectories may provide earlier signals of biological treatment resistance and complement conventional measures of disease progression. Future research should establish clinically actionable inflammatory combinations and evaluate biomarker-guided anti-inflammatory strategies alongside standard therapies. Ultimately, integrating inflammatory phenotypes with tumour molecular characteristics may facilitate earlier recognition of resistance and more precise, dynamic, and equitable breast cancer management.

To evaluate maternal, fetal, and neonatal outcomes after preconception or gestational exposure to glucagon-like peptide-1 receptor agonists and dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonists, and to assess the reproducibility of reported safety signals. Six databases plus a drug-level safety search were searched through 16 July 2026. Exposure was classified into four clinically defined time windows. Independent studies or data sources were the analytic unit; one primary comparator was selected per study, and odds ratios and risk ratios were synthesized separately. Random-effects meta-analysis, timing-stratified and dominant-study sensitivity analyses, Newcastle-Ottawa Scale assessment, and GRADE certainty assessment were used. Fourteen comparative data sources were included; 13 were quantitatively eligible and eight contributed to at least one pooled estimate. In the timing-specific analysis of major congenital malformations, four studies with verified periconceptional/first-trimester exposure yielded an odds ratio of 0.99 (95% confidence interval 0.77-1.27). A secondary pregnancy-period analysis that added one unadjusted, trimester-unspecified cohort yielded 1.00 (0.94-1.06); that cohort contributed 93.5% of the weight. Pooled preterm birth, small-for-gestational-age birth, and stillbirth analyses showed no statistically significant differences. Preeclampsia and other sparse outcomes were not pooled. Certainty was very low for all key outcomes. Current evidence does not demonstrate a clear or consistent increase in major congenital malformation risk, but very low certainty, imprecision, residual confounding, heterogeneous comparators, sparse agent-specific data, and uncertain exposure timing preclude conclusions of safety. Reported preeclampsia and renal or urinary signals have not been independently replicated.

To evaluate serum progesterone combined with transvaginal ultrasound for distinguishing ectopic pregnancy (EP) in patients with pregnancy of unknown location (PUL), and to assess diagnostic efficacy across risk stratifications. Internally unvalidated analysis included 148 PUL patients (January 2022-December 2025). Final diagnosis by surgical pathology or follow-up divided patients into EP (49) and non-EP (99; intrauterine pregnancy or natural regression). All underwent initial transvaginal ultrasound to confirm PUL. The prediction point was the 48-hour reassessment. Predictors were abnormal adnexal findings on follow-up ultrasound at 48 h, serum progesterone, and 48-hour β -hCG results available at that visit. The intended application is risk re-stratification and follow-up planning at 48-hour reassessment, not replacement of surgical/histopathological diagnosis or immediate treatment. Progesterone and β -hCG were measured; groups were compared. Logistic regression screened independent predictors. ROC curves evaluated single and combined indicators. We assessed if progesterone improved the ultrasound + M6NP model, with M6NP defined as M6 excluding initial progesterone. The EP group had lower serum progesterone, initial β -hCG, 48-hour β -hCG change rate, and endometrial thickness, and higher abnormal adnexal ultrasound detection ( P < 0.05). Multivariate analysis showed log progesterone, abnormal adnexal ultrasound, previous EP, and M6NP high-risk classification (≥5%) were independent predictors ( P < 0.05). All AUC values are apparent/in-sample estimates. Ultrasound + M6NP had an apparent AUC of 0.913; adding progesterone increased it to 0.947. In the M6NP high-risk subgroup, progesterone plus ultrasound had an apparent AUC of 0.945 and specificity of 91.67%. Because the model was developed and evaluated in the same dataset without bootstrap or internal validation, estimates are preliminary and require external validation. Internally unvalidated analysis, serum progesterone combined with transvaginal ultrasound was associated with improved apparent diagnostic accuracy for EP in PUL, especially within M6NP risk stratification. These estimates are apparent/in-sample, preliminary, and hypothesis-generating.

Sickle cell disease (SCD) has long been associated with high childhood mortality and reduced life expectancy; however, advances in newborn screening, disease-modifying therapies, and comprehensive care have substantially improved survival. As increasing numbers of women with SCD reach midlife, new challenges are emerging that extend beyond the traditional focus on fertility and pregnancy. Despite growing recognition of reproductive health issues in SCD, menopause remains an underexplored and underrecognized phase of the disease trajectory. In this Perspective, we propose a lifespan framework for women's health in SCD that extends from menarche through menopause and healthy aging. We discuss how the underlying pathophysiology of SCD-including chronic hemolysis, inflammation, endothelial dysfunction, and progressive organ injury-intersects with reproductive transitions across the female life course. We highlight emerging evidence suggesting earlier menopause in women with SCD and examine the potential implications for pain burden, cognitive health, bone health, cardiovascular risk, iron overload, and quality of life. We further explore how symptom overlap between menopause and SCD may contribute to underdiagnosis and undertreatment during midlife. At the same time, we highlight the role of protective factors-including comprehensive multidisciplinary care, the development and evaluation of menopause-specific interventions through dedicated clinical trials in individuals with SCD, reproductive health services, and coordinated lifespan care models-in supporting healthy aging and improving long-term outcomes. Finally, we argue that menopause should be recognized as a critical component of comprehensive SCD care and research. Integrating reproductive aging into clinical practice, research agendas, and health policy represents an important opportunity to improve lifelong health outcomes, strengthen women-centered care, and advance health equity for women living with SCD worldwide.

Ovarian cancer ascites creates an immunosuppressive microenvironment that compromises NK cell function, yet the underlying mechanisms remain incompletely understood. We used ascites-conditioned NK cells and assessed their mechanophenotypes, including F-actin, cortical tension, and traction force, along with CDC42 activity. Transcriptomic analysis and bidirectional pharmacological manipulation of CDC42 were performed. Ascites-conditioned NK cells exhibited a paradoxical cytoskeletal state-elevated F-actin yet reduced cortical tension and traction force-indicating a failure to translate actin polymerization into productive mechanical output. Mechanistically, ascites triggered de novo expression of the CDC42 negative regulators, CDC42EP1 and CDC42EP5, leading to suppressed CDC42 activity. Bidirectional pharmacological manipulation of CDC42 reciprocally regulated traction force and cytotoxicity, establishing a causal link between CDC42-dependent mechanics and NK cell killing. The near-perfect correlation between traction force and killing capacity positions traction force as a robust mechanobiomarker of NK cell competence. These findings uncover a previously unrecognized role for CDC42 in governing NK cell mechanics and identify CDC42 as a therapeutically actionable node for restoring anti-tumor immunity in immunosuppressive microenvironments.