Pakistan journal of pharmaceutical sciencesPeipei Li, Tuo He, Jiajia Pan, Jie Yang, Jiwen Peng
BACKGROUND: Adenomyosis is commonly associated with dysmenorrhea and heavy menstrual bleeding. Although the levonorgestrel-releasing intrauterine system (Mirena, LNG-IUS) is recommended as a first-line conservative treatment, device displacement or expulsion remains a major limitation, especially in patients with enlarged uteri or deep uterine cavities. OBJECTIVES: To evaluate the clinical efficacy and safety of the Indomethacin-GyneFix IUD (GyneFix IUD) combined with LNG-IUS in patients with adenomyosis and to assess whether uterine cavity depth influences device stability. METHODS: In this single-center prospective randomized controlled trial, 270 patients with adenomyosis were randomly assigned in a 1:1:1 ratio to the GyneFix IUD + LNG-IUS group, the ring IUD + LNG-IUS group, or the LNG-IUS-alone group (90 patients each). The primary endpoint was the rate of device displacement/expulsion at 6 months. Secondary endpoints included changes in visual analogue scale (VAS) scores, pictorial blood loss assessment chart (PBAC) scores, uterine volume, hemoglobin (Hb), serum CA125, adverse events and patient acceptance. Subgroup analysis was performed according to uterine cavity depth (≤ 9cm vs. >9 cm). RESULTS: At 6 months, the displacement/expulsion rate was significantly lower in the GyneFix IUD + LNG-IUS group (2.22%) than in the ring IUD + LNG-IUS group (10.00%) and the LNG-IUS-alone group (18.89%) (χ2=13.468, P<0.001). All three groups showed significant improvement in dysmenorrhea, menstrual blood loss, Hb and CA125 compared with baseline, without significant between-group differences (all P>0.05). Adverse event rates were comparable among groups (all P>0.05). Patient willingness to choose the same treatment again (95.12%) and willingness to recommend it (90.24%) were significantly higher in the GyneFix IUD + LNG-IUS group. In patients with uterine cavity depth >9 cm, the stability advantage of this strategy was more pronounced. CONCLUSION: GyneFix IUD combined with LNG-IUS significantly reduces device displacement/expulsion in adenomyosis, particularly in patients with deeper uterine cavities, while maintaining comparable symptom relief and safety. It may represent a more stable and acceptable long-term conservative treatment option.
Pakistan journal of pharmaceutical sciencesJun Gao, Yawen Liu, Guifang Sun
BACKGROUND: SJAMP, a natural polysaccharide compound, has demonstrated significant inhibitory effects on various tumor models. Whether it plays a role in cervical cancer is unclear. OBJECTIVES: To explore the effects of SJAMP on the mTOR/p70S6K signaling pathway and the invasion and migration abilities of cervical cancer HeLa cells. METHODS: The HeLa cells were divided into blank/solvent/polymer control groups and 1.2, 3.2 and 6.4 g/L SJAMP treatment groups. The cell proliferation, migration, invasion abilities, as well as the expression of mTOR/p70S6K protein and mRNA were detected. RESULTS: As the concentration of SJAMP increased, the proliferation, migration and invasion abilities of HeLa cells were significantly reduced (all P < 0.05) and the protein and mRNA expressions of mTOR and p70S6K also decreased in a concentration-dependent manner (all P < 0.05). CONCLUSION: SJAMP can effectively inhibit the proliferation, migration and invasion of cervical cancer HeLa cells and this inhibitory effect is strongly dose-dependent and correlates with the downregulation of the mTOR/p70S6K signaling pathway.
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia GroupJae-Seong Lee, Kye-Hwa Lee
BACKGROUND: Since its introduction in 2010, Ultrasound-guided High-Intensity Focused Ultrasound (USgHIFU) has rapidly expanded in South Korea, despite the absence of widely accepted standardized clinical protocols. This study evaluated the long-term clinical outcomes of USgHIFU and proposed a standardized MRI-integrated treatment framework incorporating MRI-based planning, treatment verification, and structured follow-up. METHODS: In this retrospective analysis, we included 2,992 patients (1,620 with uterine fibroids and 1,372 with adenomyosis) treated with USgHIFU between 2010 and 2025. Therapeutic efficacy was assessed using non-perfused volume (NPV) ratio, volume reduction rates (VRR), and reintervention rates. Long-term durability, defined as freedom from reintervention, was evaluated using Kaplan-Meier analysis in 476 patients with follow-up durations of 3-9.7 years. RESULTS: Immediate post-treatment contrast-enhanced MRI demonstrated a mean NPV ratio of 86.5 ± 7.2%, with 94.2% of patients achieving an NPV ratio ≥ 80%. At 12 months, the mean VRRs were 77.4% and 61.4% for fibroids and adenomyosis, respectively. In the long-term follow-up subset (n = 476), volume reduction was maintained and then increased, reaching 78.8% for fibroids and 66.3% for adenomyosis at 3-9.7 years. Freedom from reintervention was 99.1% at 12 months, 98.4% at 3 years, and 97.6% at 9.7 years. No major complications were observed after implementation of the standardized treatment framework. CONCLUSION: Standardized USgHIFU treatment, achieving an NPV ratio ≥ 80%, is associated with sustained long-term clinical outcomes and a favorable safety profile. These findings support the clinical value of a standardized MRI-integrated treatment framework and may contribute to future clinical standardization of USgHIFU practice.
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and GynaecologyCihan Karadağ, Gökçenur Karakelleoğlu, Levent Çelik, Kazibe Koyuncu
BACKGROUND: T-shaped uterus is associated with impaired reproductive outcomes, and the role of hysteroscopic metroplasty remains unclear. This study aimed to evaluate the impact of hysteroscopic metroplasty on in vitro fertilisation (IVF) outcomes in women with T-shaped uterus and unexplained infertility. METHODS: This retrospective cohort study included 105 women with unexplained infertility and hysteroscopically confirmed T-shaped uterus who underwent IVF between 2021 and 2024. The primary outcome was live birth rate (LBR). Unexplained infertility was defined as failure to conceive despite normal ovulation, tubal patency, and semen parameters. Fifty-six patients underwent hysteroscopic metroplasty prior to IVF, while 49 proceeded directly to IVF without surgical correction. All patients were treated using a standardised antagonist protocol with frozen embryo transfer. Implantation, biochemical pregnancy, clinical pregnancy, miscarriage, and live birth rates were compared between groups. RESULTS: Baseline demographic characteristics, ovarian reserve parameters, and IVF cycle features were comparable between groups. Implantation rates did not differ significantly (46.4% vs. 42.8%, p = 0.122). The biochemical pregnancy rate was lower in the metroplasty group (5% vs. 16%, p = 0.012). However, clinical pregnancy rate (41% vs. 26.5%, p = 0.024) and live birth rate (33.9% vs. 18.3%, p = 0.016) were significantly higher in women who underwent metroplasty. Miscarriage rates were similar between groups. CONCLUSIONS: Hysteroscopic metroplasty was associated with improved clinical pregnancy and live birth rates in women with T-shaped uterus undergoing IVF. Prospective randomised studies are warranted to confirm these findings. However, the observed improvement may reflect a combined effect of anatomical cavity restoration and endometrial injury associated with the surgical procedure.
Human vaccines & immunotherapeuticsBiyun Luo, Zian Lin, Jianan Chen, Yijing Wang, Xinli Peng, Weikang Yang, Wensheng Chen, Lijun Zhang, Jiao Liu, Yan Ding, Fan Hong, Gang Liu, Yuying Zhang
Extensive evidence confirms the high effectiveness of human papillomavirus (HPV) vaccines in young girls; however, real-world data on vaccine effectiveness (VE) among women vaccinated at ages 18-45 remain limited, particularly in China, where HPV status at vaccination is often unknown. We conducted a population-based matched test-negative design study using linked cervical cancer screening and immunization records in Shenzhen, China. Cases positive for vaccine-type high-risk HPV (hrHPV) DNA were matched 1:1 with negative controls by age, screening date, household registration, and screening type. VE for at least one dose was estimated using conditional logistic regression and stratified by time since vaccination, vaccine valency, and age at vaccination. Among 7,060 matched pairs, overall VE increased significantly with time since vaccination: 6.4% (95% CI: -3.9% to 15.7%) at <1y, 17.9% (5.5% to 28.7%) at 1-<2y, and 40.2% (29.6% to 49.2%) at ≥2y. Among women vaccinated ≥2y earlier, VE against HPV16/18 was 48.4% (33.7% to 59.8%) for 2-/4-valent vaccines and 54.4% (26.5% to 71.7%) for the 9-valent vaccine. Significant protection at≥2y was observed across all age-at-vaccination groups: 45.7% (25.0% to 60.7%) for ages 18-26, 39.6% (23.5% to 52.4%) for ages 27-35, and 35.5% (12.6% to 52.4%) for ages 36-45. In conclusion, HPV vaccination confers moderate protection against vaccine-type hrHPV DNA positivity among Chinese women vaccinated at ages 18-45. However, as this outcome reflects a single-time-point surrogate virologic endpoint rather than persistent infection or clinical disease, adult women should continue regular cervical cancer screening.
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and GynaecologyFeng Sun, Mengyao Huan, Huimin Niu, Chuning Lin, Xinyi Zhang, Yuxin Liu, Feng Jiang, Chuyan Wu
BACKGROUND: Polycystic Ovary Syndrome (PCOS) imposes substantial metabolic and reproductive burdens. Exercise has emerged as a crucial lifestyle intervention, and corresponding scientific interest has expanded. This study provides a comprehensive bibliometric analysis of global research on the intersecting PCOS and exercise. METHODS: Relevant publications (2005-2025) were collected from the Web of Science Core Collection (WoSCC). CiteSpace, VOSviewer, and bibliometrix were applied to map publication trends, international collaboration patterns, and evolving research hotspots. RESULTS: A total of 1,146 publications were identified, demonstrating sustained growth. The United States and Australia dominated productivity, collaborating primarily with India, the United Kingdom (UK), and Switzerland. Key research hotspots included metabolic syndrome, endothelial function, cardiovascular disease, and increasing emphasis on exercise-based interventions. Monash University and the University of Adelaide played central roles in institutional networks. Emerging themes, including oxidative stress and anxiety, have emerged in the broader PCOS literature and are closely linked to exercise-related biological pathways. CONCLUSIONS: Exercise is an increasingly prominent research focus in PCOS management. This analysis outlines the field's structural and thematic evolution and identifies opportunities for advancing scientific understanding. Strengthened international and multidisciplinary collaboration remains essential.
Human vaccines & immunotherapeuticsFakher Rahim, Ümit Atasever
Despite widespread HPV vaccination, a comprehensive synthesis across populations and cancer outcomes is lacking. This umbrella review evaluates HPV vaccination's population impact on infection, precancerous lesions, and invasive cancers. We searched five databases for meta-analyses reporting prophylactic HPV vaccine outcomes up to Jan 2026. Two reviewers performed selection, data extraction, AMSTAR-2, and GRADE. From 34 meta-analyses, RCTs in HPV-naïve women showed 99% efficacy (95% CI: 98-99%) against HPV16/18 infection, 96% against CIN2+, and 89% against anogenital warts. Observational studies found relative risks of 0.12-0.36 (HPV16/18) and 0.48-0.68 (CIN2+). In men, effectiveness against warts was 74-90%. Ecological studies reported reductions in cervical cancer of 57-88%. GRADE certainty was high for infection/warts, moderate for precancer, and low for invasive cancer. HPV vaccination is highly effective. Invasive cancer prevention evidence is promising but emerging. Further research in immunocompromised populations is needed.
Journal of enzyme inhibition and medicinal chemistryYinxing Zhu, Hanying Wu, Xiaohao Liu, Rui Li, Min Jiang
EGFR L858R is an activating mutation associated with aberrant EGFR signalling, and molecules capable of recognising this mutant remain of research interest. In this study, a virtual peptide library containing 59 319 heptapeptides was screened against the EGFR L858R crystal structure, leading to the identification of four peptides with favourable predicted binding ability. Among them, Peptide-1 showed the strongest binding affinity in MST assays (Kd = 0.35 ± 0.02 μM), with higher affinity than the reference peptide DTP-1. Integrated structural and dynamic analyses showed that Peptide-1 could form a relatively stable binding conformation with EGFR L858R. Peptide-1 reduced the viability of SKOV3, OVCAR3, and CaOV3 cells, showed weaker effects on IOSE-80 cells, and its activity was markedly attenuated after EGFR-targeting shRNA transduction. In addition, Peptide-1 decreased Cyclin D1 mRNA expression and increased Caspase-3 mRNA expression. These findings indicate that Peptide-1 can be further investigated as an EGFR L858R-targeting peptide.
Global public healthKallin C Hermann, Alejandro Andrés Peralta Chiriboga, Kevin T Fuji, Anne L O'Keefe, María Sol Jurado Vaca, Abubakar Tauseef, Karina Kletscher, Jason Beste
Human papillomavirus (HPV) is estimated to cause 99.7% of all cervical cancers and is the main cause of anal cancer. Despite global progress, Ecuador has one of the highest cervical cancer mortality rates in Latin America, with fluctuating vaccine uptake since its introduction for girls in 2014 and expansion to boys in 2024. Semi-structured interviews were conducted with parents of vaccine-eligible children and healthcare providers (HCPs) in Quito. The interviews explored HPV knowledge, perceptions, and access to vaccination. The transcripts were analysed thematically. Forty-one participants (32 parents, 9 HCPs) were interviewed. Eight themes emerged: (1) parents desire more information about HPV, (2) neither parents nor HCPs associate HPV with cancer in men, (3) mothers have more knowledge than fathers, (4) fear of side effects contributes to vaccine hesitancy, (5) fear of sexual promiscuity does not influence vaccination, (6) HPV vaccine administration is conducted at schools, but parents and providers desire better support from these schools, (7) parents perceive a lack of information as their greatest barrier, while HCPs perceive carelessness among parents, and (8) age guidelines for vaccination can be confusing. HPV vaccine uptake is shaped by individual and system-level barriers. Aligning provider-parent perspectives and strengthening school- and community-based education may improve vaccination.
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and GynaecologyRenée H Visser, Emma E Don, Wouter W J K Hehenkamp, Judith A F Huirne, Anne Timmermans, Robert A De Leeuw
BACKGROUND: Data on reproductive outcomes after myomectomy in women of advanced reproductive age are limited. This study aimed to assess post-myomectomy age-specific ongoing pregnancy rates and associated impact factors for women aged 37 years and older. METHODS: This observational retrospective cohort study was conducted at a tertiary fibroid-expertise centre in Amsterdam, the Netherlands. Women aged 37 years or older with an active wish to conceive who underwent myomectomy between 2004 and 2022 were included. Data were retrieved from patient records and a questionnaire. The primary outcome was age-specific ongoing pregnancy rates. A multivariable logistic regression analysis was performed to identify predictive factors. RESULTS: A total of 100 patients were included in the analysis. Follow up was a median of 24 months. The ongoing pregnancy rate was 36%, with an age-related trend showing rates of 46.4% in women under 40 years of age compared to 22.7% in women 40 years and older. The overall pregnancy rate was 44% resulting in 49 pregnancies of which 63.3% were live births, 28.6% miscarriages, 8.1% currently ongoing pregnancies and no intrauterine foetal deaths. The number of fibroids and age (<40 and ≥40 years) are both variables that significantly decrease the odds of achieving an ongoing pregnancy. CONCLUSION: Ongoing pregnancy rates after myomectomy in this cohort of advanced age was relatively high, with an age-related decline in fertility. Women of advanced reproductive age can still achieve pregnancy after myomectomy, but these changes decrease after 40 as known from previous literature.
Molecular and cellular endocrinologySuijian Wang, Kui Wang
BACKGROUND: Polycystic ovary syndrome (PCOS) frequently co-occurs with obesity, insulin resistance, dyslipidaemia and metabolic syndrome (MetS). However, whether this metabolic burden represents secondary comorbidity or an intrinsic component of PCOS genetic architecture remains unclear. METHODS: We used genomic structural equation modelling to construct female- and male-specific hierarchical MetS latent factors from six sex-stratified cardiometabolic GWAS, including BMI, waist circumference, triglycerides, HDL cholesterol, type 2 diabetes and fasting glucose. Sex-specific MetS genetic architecture was evaluated using latent factor GWAS, sex-difference testing, MiXeR, MAGMA and GSA-MiXeR. To assess the relationship between MetS liability and PCOS, we performed CPASSOC, conjunctional FDR, Bayesian colocalization, GWAS-by-subtraction and GenomicSEM-based mediation analysis. RESULTS: Female and male MetS factors shared a highly overlapping polygenic backbone, but their genetic correlation was significantly below unity. Among comparable lead variants, 9.1% showed sex-dimorphic effects, and MiXeR estimated an approximately fourfold larger female-specific causal component than the male-specific component. Cross-trait analysis identified 45 candidate pleiotropic loci linking PCOS with the female MetS factor, 34 conjFDR-supported shared loci and 10 loci with strong Bayesian colocalization evidence, including FTO, ERBB3, FGFR1, KLF16 and TEX41. GWAS-by-subtraction showed that 16.7% of PCOS genetic variance was shared with female MetS, whereas 83.3% remained MetS-independent and retained stronger reproductive-endocrine features. Variant-level mediation further showed that MetS-mediated effects were locus-specific rather than a global amplifier of PCOS risk. CONCLUSIONS: This study redefines the metabolic comorbidity of PCOS as a separable, female-biased genetic dimension embedded within, but distinct from, the predominant reproductive-endocrine genetic architecture of PCOS. These findings provide a genetic framework for resolving reproductive-metabolic heterogeneity in PCOS and may inform future risk stratification and precision management of metabolic complications in women with PCOS.
Gynecological endocrinology : the official journal of the International Society of Gynecological EndocrinologyCamil Castelo-Branco, Svetlana Vujovic, Alessandro D Genazzani, Mark Brincat, Blazej Meczekalski, Petra Stute, Andrea R Genazzani, Geraldine Brichant, Raoul Or…
BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder whose terminology inadequately reflects its systemic nature. The proposed renaming to polyendocrine metabolic ovary syndrome (PMOS) aims to better represent its pathophysiology. OBJECTIVE: To present the European Society of Gynaecology (ESG) position regarding the proposed terminology change and its implementation. METHODS: Expert consensus and narrative synthesis of current scientific evidence and international recommendations. RESULTS: ESG supports a structured, patient-centered transition strategy. Recommendations include prioritizing patient communication, implementing a gradual transition with prolonged dual terminology use, and integrating the new terminology systematically into scientific and educational frameworks. The importance of interdisciplinary clarity and the central role of gynecological endocrinology are emphasized. CONCLUSION: A phased and clearly communicated transition will enhance conceptual accuracy while preserving patient understanding, continuity of care, and clinical coordination.
Gynecological endocrinology : the official journal of the International Society of Gynecological EndocrinologyElene Asanidze, Alla Vash-Margita, Besik Asanidze, Mariam Kharaishvili, Maia Chiokadze, Ana Jibladze, Jenaro Kristesashvili
Peripheral precocious puberty (PPP) is a rare condition in early childhood, particularly among girls under 3 years of age. One cause of PPP is functional ovarian cysts that secrete estrogen at levels sufficient to trigger the development of premature secondary sexual characteristics. Unilateral ovarian agenesis is an uncommon congenital anomaly. The coexistence of both conditions in a single patient is extremely rare and poses unique diagnostic and management challenges. We report the case of a 2-year and 10-month-old girl presenting with concurrent breast development, pubarche, and recurrent vaginal bleeding. Pelvic imaging revealed a cyst in the left ovary and agenesis of the right ovary. Laparoscopy confirmed absence of the right ovary and ipsilateral fallopian tube. Based on clinical, hormonal, and radiologic findings, a diagnosis of PPP due to a functional ovarian cyst was made. Given the rapid progression of symptoms, increase in cyst size, and concern for torsion, a short observation period of three months was followed by ovarian-preserving laparoscopic cystectomy. Histopathology confirmed a benign follicular cyst. Postoperatively, the patient experienced partial regression of pubertal signs and complete resolution of vaginal bleeding. This case highlights the importance of individualized decision-making in managing PPP,especially in the presence of congenital anomalies.
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and GynaecologyPedro Belchín Fernández, Virginia Calvente, Maria Jose Gómez Roso, Eva González Expósito, Ana Silván Bueno, Maya Aparicio Fluge, Daniel Ordoñez Pérez
BACKGROUND: PCOS is frequently associated with metabolic disturbances, including a high prevalence of insulin resistance and compensatory hyperinsulinemia, which can impair reproductive outcomes. Previous evidence indicates that combining myo-inositol and D-chiro-inositol in a specific 3.6:1 ratio may support ovarian physiology and reproductive performance in women with PCOS. This study aimed to evaluate whether taking a 3.6:1 MYO:DCI inositol-based supplement enriched with antioxidants for at least 1 month prior to controlled ovarian stimulation could improve IVF-ICSI outcomes. METHODS: A retrospective observational cohort study was conducted, including 92 women diagnosed with PCOS according to the Rotterdam criteria. Patients were allocated to 2 groups: those who used the MYO:DCI 3.6:1 antioxidant-containing supplement (Group 1) and those who followed conventional supplementation (Group 2). Outcomes assessed included ovarian response, fertilization rates, blastocyst development and pregnancy results. RESULTS: The number of retrieved oocytes (21.5 in Group 1 vs. 20.7 in Group 2; p = 0.56) and the metaphase II oocyte rate (72.06% in Group 1 vs. 71.23% in Group 2; p = 0.68) were comparable between both groups. Notably, Group 1 achieved higher fertilization rates (77.66% vs. 71.61%; p = 0.0314) and a lower proportion of cycles without at least one good-quality blastocyst to transfer (4.35% vs. 17.39%; p = 0.0450). In addition, both clinical and ongoing pregnancy rates were significantly improved in the supplemented group (54.39% vs. 42.65%; p = 0.0203; 45.61% vs. 36.76%; p = 0.0033). CONCLUSION: This observational pilot study suggests that a pre-treatment with 3.6:1 MYO:DCI ratio and antioxidant-based supplement taken for at least 1 month prior to ovarian stimulation may improve oocyte quality and increase pregnancy rates. These findings, while promising, require confirmation in larger prospective trials.
Human vaccines & immunotherapeuticsSara Cooper, Charles S Wiysonge, Ngcwalisa A Jama, Natalie Leon, Jill Ryan, Edison J Mavundza, Rosemary J Burnett, Asahngwa Constantine Tanywe, Dane Witten, Be…
The human papillomavirus (HPV) vaccine is one of the most powerful tools in cancer prevention and is central to global efforts to eliminate cervical cancer as a public health problem. Yet worldwide uptake remains suboptimal. Our 2025 Cochrane qualitative evidence synthesis - comprising 71 studies from diverse geographic and socioeconomic settings - provides the most comprehensive global understanding to date of caregivers' and adolescents' views and practices regarding HPV vaccination, and the reasons why some are reluctant to receive the vaccine. Our review found HPV vaccine decision-making to be influenced by a complex web of socio-cultural, political and trust-related factors, beyond awareness or a simple evaluation of vaccine benefits and risks. We synthesized these factors into eight overarching themes. Together these provide a novel conceptual framework of the multi-level, interacting influencing factors, distinguishing it from more narrow, individual HPV vaccination acceptance frameworks. In this commentary we describe this conceptual framework and propose how it might be used to inform strategies for improving HPV vaccine uptake in ways that are more person-centered, equitable and ultimately effective. As countries worldwide aim to upscale and optimize HPV vaccination programs, incorporating insights from this review into HPV vaccination policy, program design and service delivery is essential and urgent.
Human vaccines & immunotherapeuticsJing Bai, Xiao-Li Cui, Si-Jia Bo, Li Sun
To identify predictive biomarkers for immunotherapy response in advanced/recurrent cervical cancer by evaluating peripheral blood indicators including T-cell subsets and serum biomarkers. This prospective study (June 2022-July 2024) enrolled 50 patients with stage III-IVa or recurrent cervical cancer receiving first-line immunotherapy combined with chemo/radiotherapy from Qingdao Central Hospital network. We analyzed baseline CD4+/CD8+ T-cell percentages and post-treatment (after one course) levels of CA125, SCCA, T-cell subsets, and PD-1 expression on T-cells using logistic regression (treatment efficacy，comparing 36 responders vs. 14 non-responders) and Cox regression (prognosis, with disease progression or death events occurring in 26 patients). Treatment response was significantly associated with: (1) baseline CD4+ T-cell percentage and (2) post-treatment CA125/SCCA levels, CD8+ T-cell percentage, and PD-1 expression on both CD4+/CD8+ T-cells (all p < .05). Prognostic factors identified by Cox regression included these same markers plus post-treatment CD4+ T-cell percentage. Optimal responders showed: high baseline CD4+ T-cells, low post-treatment CA125/SCCA, elevated CD4+/CD8+ T-cells, and reduced PD-1 expression. Peripheral T-cell subsets and serum biomarkers show significant associations with predicted immunotherapy outcomes. High baseline CD4+ T-cells with post-treatment normalization of immune markers (increased T-cells, decreased PD-1+ cells, and tumor antigens) are associated with a higher likelihood of benefiting from immunotherapy. It should be noted that this study has limitations, including a modest sample size and the assessment of biomarkers at only a single post-treatment time point, which may affect the generalizability of the findings. These peripheral blood biomarkers may represent a minimally invasive approach for exploring treatment dynamics and are considered worthy of further investigation as potential adjuncts in the context of personalized immunotherapy for advanced cervical cancer. However, their predictive performance and clinical utility remain to be validated in larger, independent cohorts before any clinical application can be considered.
Annals of diagnostic pathologyYan Wang, Yeli Yao, Haiyan Shi, Weiguo Lu, Bingjian Lu
HPV-associated adenocarcinoma in situ (AIS) is the main precursor to endocervical adenocarcinoma. The differential immunoprofiles remain poorly characterized among HPV-associated AIS variants (such as usual-type and stratified mucin-producing intraepithelial lesion [SMILE]). This study aimed to investigate the expression of stem cell markers (SOX2 and SOX17) in 159 HPV-associated AIS (124 usual-type, 11 with intestinal differentiation, 24 SMILE) by immunohistochemistry. Compared to normal endocervical glands, AIS exhibited significantly increased expression of SOX2 (69.2% vs. 0, p < 0.001), but decreased SOX17 (40.9% vs. 98.1%, p < 0.001). Positive SOX2 and negative SOX17 had a specificity of 100% and 98.1% in the differential diagnosis of AIS from normal glands, respectively. SOX2 expression was significantly higher in SMILE (22/24, 91.7%) than in usual-type AIS (80/124, 64.5%, p = 0.030). In contrast, SOX17 expression was absent in all SMILE (0/24) and most AIS with intestinal differentiation (1/11, 9.1%), but was significantly higher in usual-type AIS (64/124, 51.6%, p < 0.001). The SOX2/SOX17 composite profile may aid in the diagnosis of AIS and its variants. The SOX2-positive (overexpression) /SOX17-negative profile suggest a divergent pathway with squamous differentiation potential in SMILE. These findings provide novel insights into the cellular histogenesis of AIS variants.
Gynecological endocrinology : the official journal of the International Society of Gynecological EndocrinologyFrancesco La Torre, Eleonora Nardi, Francesca Bonechi, Silvia Vannuccini, Flavia Sorbi, Massimiliano Fambrini, Francesca Castiglione, Gian Franco Zannoni, Andr…
BACKGROUND: Adenomyosis is a benign uterine disease that has been associated with endometrial proliferative disorders. Adenomyosis and endometrial cancer (EC) are sex-steroid-dependent conditions that may coexist, but their estrogen receptor (ER) and progesterone receptor (PR) signaling landscape is poorly defined. OBJECTIVE: The present multicenter study aimed to characterize the expression of estrogen (ESR1/ESR2 plus the coregulators NCOA1, CCND1, BRCA1) and progesterone (PGR plus FOXO1, and CYP26A1) receptor pathway-related genes in hysterectomy specimens of patients with adenomyosis and coexisting EC. METHODS: Specimens from three groups of patients (n = 10 per group) referred to two tertiary hospitals were studied: adenomyosis plus EC (Group 1), only adenomyosis (Group 2), and only EC (Group 3). Gene expression was assessed by droplet digital PCR using a compartment-matched design. Analysis was compartment-specific, and no cross-compartment comparisons were performed. RESULTS: Compared with isolated adenomyosis, adenomyotic lesions from uteri with coexisting EC showed higher ESR2 (p = 0.0082) and BRCA1 (p = 0.0007) expression, with no differences in ESR1, NCOA1, or CCND1. PR-related gene expression (PGR, FOXO1, and CYP26A1) did not differ between adenomyosis groups. CONCLUSION: Although preliminary, the present findings indicate that adenomyosis coexisting with EC is characterized by elevated expression of ESR2 and BRCA1, suggesting an enriched ER-related microenvironment that may be relevant to local estrogen responsiveness.
Annals of medicineLiaoyao Wang, Yuejie Lu, Hejing Pan, Xuanlin Li, Le Luo
OBJECTIVES: This meta-analysis aimed to evaluate the association between endometriosis (EM) and cardiovascular disease (CVD) risk by synthesizing evidence from large-scale cohort studies, with emphasis on subtype-specific risks and geographic disparities. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for cohort studies published until December 2024. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses stratified CVD subtypes (e.g. ischemic heart disease, atrial fibrillation), continents, and country development levels. Heterogeneity and publication bias were assessed via I2 statistics, sensitivity analyses, and Egger's test. RESULTS: Eleven cohort studies (n = 3,100,610 participants) were included. EM was associated with a 22% increased risk of all-cause CVD (HR = 1.22; 95% CI: 1.08-1.38; I2 = 94.6%). Subgroup analyses revealed elevated risks for myocardial infarction (HR = 1.29; 95% CI: 1.10-1.50), coronary artery disease (HR = 1.47; 95% CI: 1.29-1.67), and cerebrovascular events (HR = 1.18; 95% CI: 1.12-1.25), but not heart failure. Geographic disparities were significant, with higher CVD risks in Asian (HR = 1.36; 95% CI: 1.25-1.48) and North American cohorts (HR = 1.37; 95% CI: 1.16-1.61) compared to European populations (HR = 0.93; 95% CI: 0.64-1.34). CONCLUSIONS: EM is independently associated with an elevated risk of CVD, particularly for coronary artery disease and myocardial infarction. These findings underscore the need for targeted cardiovascular monitoring in EM patients, particularly in high-risk populations.
Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicineShuai Zhang, Dingli Ye, Yuting Xiu, Haifeng Liu, Fanxu Meng, Xinmin Zhang, Zhicheng Wang, Hong Yu, Yufei Han, Xi Chen, Baosheng Sun
PURPOSE: Radiation proctitis (RP) is a common complication following radiotherapy for cervical cancer, for which accurate pre-treatment prediction remains challenging. This study aimed to develop and validate a multimodal machine learning model that incorporates habitat heterogeneity analysis from planning CT images to predict RP risk at the individual level. METHODS: In this retrospective study, 100 patients with cervical cancer treated with radiotherapy were enrolled (53 RP-positive, 47 RP-negative). A comprehensive dataset of 2783 multimodal features was collected, encompassing sociodemographics, clinical parameters, dosimetry, conventional radiomics, and novel habitat heterogeneity features derived from planning CT images. Key predictors were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Four machine learning models (Logistic Regression, Random Forest, XGBoost, LightGBM) were optimised and compared via 10-fold cross-validation. The best-performing model was validated on an independent test set (n = 30). Model interpretability was analysed using Shapley Additive exPlanations (SHAP), and a clinical nomogram was constructed for individualised risk assessment. RESULTS: Logistic regression demonstrated the best predictive performance, achieving an area under the curve (AUC) of 0.929 on the training set (n = 70) and 0.869 on the independent test set. SHAP analysis identified Rectum-V50 as the most important predictor of RP, followed by habitat heterogeneity features such as Habitat2_Flatness. The model showed good calibration and provided significant clinical net benefit across a wide range of threshold probabilities (0.01-0.99) in decision curve analysis. The final nomogram, based on the 15 selected features, effectively stratified patients into low-, intermediate-, and high-risk groups. In the test set, all 15 patients (100%) stratified as high-risk developed RP. SHAP analysis confirmed intuitive, non-linear relationships between feature values and predicted risk. CONCLUSION: A multimodal machine learning model integrating features of habitat heterogeneity accurately predicts RP risk in patients with cervical cancer undergoing radiotherapy. The developed nomogram provides a clinically practical tool for individualised risk stratification, potentially facilitating early intervention.