Background Diabetic kidney disease (DKD) remains a leading cause of end-stage renal disease worldwide. Despite advances in renin–angiotensin–aldosterone system (RAAS) inhibitors, sodium–glucose cotransporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRAs), substantial residual renal risk persists. Endothelin-1 (ET-1), primarily via endothelin A (ETA) receptor activation, plays a central role in glomerular injury, inflammation, and fibrosis. Methodology This narrative review summarizes current evidence on the mechanistic basis and clinical translation of ETA receptor antagonists (ERAs) in DKD. Relevant preclinical and clinical studies were identified through structured literature searches of PubMed, Embase, and Web of Science, focusing on mechanistic insights, therapeutic efficacy, and safety profiles. Results Preclinical studies across diabetic models (e.g., streptozotocin-induced and db/db mice) demonstrate that ETA antagonism reduces glomerular hypertension, preserves podocyte integrity, and attenuates inflammatory and fibrotic signaling pathways. In clinical settings, the SONAR trial showed that atrasentan significantly reduced the risk of renal events (hazard ratio ~0.65) and achieved approximately 30–40% reduction in urinary albumin-to-creatinine ratio (UACR) in selected responders. However, ERA therapy is associated with fluid retention and increased heart failure risk. Notably, a biomarker-guided enrichment strategy, based on early albuminuria response during a run-in phase, improved patient selection and benefit–risk balance. Conclusion ETA receptor antagonists represent a promising mechanism-based adjunctive therapy for DKD. Their future role is likely to be integrated within combination regimens alongside SGLT2 inhibitors and MRAs, guided by biomarker-driven precision medicine approaches to optimize efficacy while minimizing adverse effects.

Background Circular RNAs (circRNAs), a conserved class of non−coding RNAs, are hypothesized to play functional roles in diabetic retinopathy (DR), yet their expression landscape and molecular involvement in retinal tissue remain poorly defined. Methods A streptozotocin−induced diabetic mouse model (C57BL/6J, male, n=40) was established, with diabetes confirmed by persistent hyperglycemia (fasting blood glucose >300 mg/dL). Retinal function was assessed by electroretinography (ERG) and vascular pathology by fluorescein fundus angiography (FFA) at 12 weeks post−induction. Retinal circRNA profiles were obtained via microarray analysis. Bioinformatic tools were used to predict circRNA-miRNA interactions, and Gene Ontology (GO) analysis was applied to annotate potential target genes. Differential expression of selected circRNAs was validated by quantitative PCR (qPCR). Results Diabetic mice exhibited sustained hyperglycemia, reduced body weight, significant declines in ERG a and b wave amplitudes, and early microangiopathy evident on FFA. Microarray profiling identified 21 dysregulated circRNAs (3 upregulated, 18 downregulated), classified as antisense, exonic, intronic, or intragenic. Bioinformatics reconstruction revealed a circRNA-miRNA network with shared microRNAs (miRNAs), and GO enrichment highlighted processes including transcriptional regulation and cancer−related signaling. qPCR confirmed the expression changes of four circRNAs. Cross−species alignment showed high sequence homology between four murine circRNAs and human orthologs. Conclusion This study identifies 21 conserved circRNAs with altered expression in the diabetic retina, supporting their potential role as competitive endogenous RNAs (ceRNAs) and implicating them in DR pathogenesis.

Background Missing data is common in observational studies, and even more so in type 2 diabetes mellitus with mild cognitive impairment(T2DM-MCI), which limits the completion of assessments. We evaluated the extent, current reporting, and handling of missing data, as well as the prevailing research trends in observational studies related to T2DM-MCI. Methods A systematic search of PubMed, Embase, and Cochrane Library was conducted from January 2020 to April 2025 to identify observational studies related to T2DM-MCI. Bibliometrics was performed using VOSviewer and CiteSpace to evaluate publishing trends, authors, journals, and keywords. The reporting and handling of missing data were assessed according to the guidelines recommended by STROBE and Sterne et al., with a focus on the recording, causes, mechanisms, processing methods, and sensitivity analysis of missing data. Data analysis was conducted using SPSS 26, and visualization was performed using Origin Pro 2024. Results Among the 4,471 screened records, 88 studies (78 in English and 10 in Chinese) were included in this analysis. Among the 78 English articles, the annual publication volume exhibited fluctuations, peaking in 2024. Chinese institutions and authors led in research output. Diabetes, Metabolic Syndrome, and Obesity had the highest publication volume (7, 8.97%). Keyword identified five clusters: 1) resting-state functional magnetic resonance imaging, 2) metabolic disorders, 3) clinical assessment tools, 4) molecular mechanisms, and 5) emerging fields such as the gut microbiome. Missing data Only 22.7% (n = 20) of the studies quantified the missing data, with an average of 9.1%. Among studies with missing data (n = 23), 52.2% (n = 12) provided reasons for missing data, primarily citing poor quality of data collection (41.7%) and loss to follow-up (41.7%). Complete case analysis was the predominant method for addressing missing data (93.3%). No study articulated the hypothesized mechanisms underlying the missing data, and only 4.4% (n = 1) performed a sensitivity analysis. Conclusion In the domain of T2DM-MCI, research outcomes post-COVID-19 pandemic indicate a rebound, with China maintaining a leading position in scientific research output. However, the reporting of missing data remains ambiguous, and the methods employed to handle such data are insufficient, which may potentially introduce bias. Systematic Review Registration https://doi.org/10.17605/OSF.IO/EZDXM .

Endocrine-disrupting chemicals (EDCs) interfere with hormone synthesis, signaling, and metabolism, leading to reproductive, metabolic, and neuroendocrine dysfunction. Non-chemical environmental endocrine stressors, including electromagnetic fields, noise, artificial light at night, and thermal stress, can disrupt endocrine homeostasis, alter neuroendocrine and hormonal function, affect signaling pathways, oxidative stress responses, and circadian rhythms. Unlike classical EDCs, which primarily exert their effects by direct binding to hormone receptors and metabolic enzymes, non-chemical endocrine disruptors predominantly act through central regulation of hypothalamic-pituitary-organ axes. EDCs, especially their biochemically active secondary metabolites, disrupt endocrine homeostasis by directly binding target hormone receptors or enzymes and then interacting with the hypothalamus-pituitary-organ axes. These physical stressors modulate molecular pathways, including MAPK and NF-κB signaling, oxidative stress responses, and circadian rhythm regulation, thereby affecting reproductive and neuroendocrine functions. Their physiological and biochemical effects depend on exposure intensity, duration, and timing; these effects vary according to sex and species. Non-chemical or biochemical endocrine disruptors may exhibit adverse or beneficial effects, depending on exposure conditions, and can modulate major endocrine hormones and inflammatory mediators, supporting their therapeutic applications. Music therapy, cryotherapy, thermotherapy, phototherapy, and pulsed electromagnetic field therapies are used to reduce inflammation, enhance circulation, facilitate musculoskeletal recovery, treat neonatal jaundice, and manage diverse clinical conditions. This review aims to explain non-chemical environmental disruptors, their partially overlapping mechanisms that target the same hormonal, circadian, and cellular signaling pathways, and to discuss their potential therapeutic applications.

Objective To compare the 12-week effectiveness and safety of dydrogesterone monotherapy versus estradiol–dydrogesterone (E2/DYD) combination therapy in women with perimenopausal symptoms in a real-world clinical setting. Methods This retrospective cohort study included 150 women treated at a tertiary gynecological outpatient clinic between July 2022 and January 2025 (dydrogesterone: n=60; E2/DYD: n=90). The primary endpoint was change in the Kupperman Menopause Index (KMI) from baseline to week 12. Repeated measures were analyzed using linear mixed-effects models. Secondary outcomes included clinical response (≥50% KMI reduction), endometrial thickness change, and adverse events. Continuous outcomes were evaluated using adjusted linear regression models, and binary outcomes were analyzed using Firth penalized logistic regression. Results At 12 weeks, KMI decreased by 8.0 ± 6.6 points in the dydrogesterone group and 12.5 ± 7.4 points in the E2/DYD group (adjusted mean difference −4.51, 95% CI −6.90 to −2.12; p<0.001). Clinical response occurred in 31.5% and 51.2% of participants, respectively (adjusted OR 2.08, 95% CI 1.02–4.45; p=0.042). Improvements in vasomotor and mood-related symptoms were more pronounced in the combination group. Endometrial thickness increased modestly in the E2/DYD group (+0.60 mm), with week-12 mean values remaining within physiologic ranges. Any adverse event was reported in 11.1% versus 31.7% of participants (adjusted OR 3.55, 95% CI 1.29–9.77; p=0.014), predominantly mild and self-limited events. Conclusion In this real-world cohort, E2/DYD combination therapy was associated with greater short-term symptom reduction compared with dydrogesterone monotherapy. Although adverse events were more frequent with combination therapy, they were generally mild and clinically manageable, and no concerning endometrial safety signals were observed over 12 weeks. As a retrospective observational study, causal conclusions cannot be drawn, and these findings should be regarded as hypothesis-generating. They provide real-world contextual evidence to inform clinical discussions around hormone therapy selection in perimenopausal care, pending confirmation in prospective randomized trials.

Introduction To determine if endometrial preparation protocols for frozen embryo transfers (FET) impact clinical and neonatal outcomes. Methods A monocentric cohort study including all first autologous FET cycles of a single blastocyst from January 1st, 2020 to September 30th, 2023. The primary endpoint was live birth (LBR). Secondary endpoints included hCG-positive pregnancy (> 100 IU/l), ongoing pregnancy (OPR), miscarriage, birthweight and term. Outcomes were also analyzed by subgroup: Day 5/Day 6 embryos. Among the 2982 FET cycles, 1507 (50.5%) were artificial cycles (AC) and 1475 (49.5%) were cycles with a corpus luteum (CLC). Univariate and multivariate analyses were performed using logistic regression models adjusting on age at transfer, age at oocyte retrieval, body mass index (BMI), indication and duration of infertility, IVF/ICSI, AMH, embryo quality, ovulatory status and year of transfer. Results Age at the time of transfer (35.3 vs. 36.0 years old) and age at oocyte retrieval (34.8 vs. 35.4 years old) were significantly lower in AC compared to CLC. After adjustment, CLC significantly increased LBR (aOR = 1.39 [1.12;1.73], P = 0.003) and OPR (aOR = 1.39 [1.12;1.74], P = 0.003) and significantly decreased miscarriage (aOR=0.63 [0.49;0.79], P = 0.0001) compared to AC. In subgroup analyses, Day 5 embryos had significantly higher LBR, OPR, hCG-positive rates and lower miscarriage rates compared to Day 6 embryos. Term of birth did not differ between the two groups. Conclusion Our study pleads for a preferential use of CLC protocols for endometrial preparation for FET in ovulatory women.

This study aimed to investigate how levels of serum follicle-stimulating hormone (FSH) on Day 7 of ovarian stimulation are related to the number of oocytes retrieved, and identify any cutoff or threshold point in protocols using gonadotropin-releasing hormone (GnRH) antagonists. We examined data from January 2017 to June 2024, covering 9,969 cycles from 7,981 patients using GnRH antagonists as part of in vitro fertilization processes. We found a complex link between serum FSH and oocyte collection. Lower serum FSH on Day 7 was associated with collection of fewer oocytes (β = −0.531, p < 0.0001), and different levels were associated with changes in the number of oocytes collected. The key point was 9.13mIU/mL. If serum FSH exceeded 9.13 mIU/mL on Day 7, each 1mIU/mL increase reduced the number of oocytes collected by 0.07 (effect β = −0.07, 95% confidence interval [CI] −0.10 to −0.05, P < 0.0001). When serum FSH was below 9.13 mIU/mL, each 1 mIU/mL rise increased the number of oocytes collected by 1.18 (effect β = 1.18, 95% CI 0.95 to 1.41, P < 0.0001). This association suggests that it may be possible to improve ovarian reaction by raising the FSH dose if serum FSH is under 9.13 mIU/mL. However, if serum FSH is already over 10 mIU/mL, it seems likely that other steps may be needed to increase ovarian reaction, although these hypotheses will need to be tested in future studies.

Introduction Turner Syndrome (TS) is a chromosomal disorder characterized by partial or complete monosomy of the X chromosome. Approximately 5–10% of patients with TS harbor Y chromosome material, which is associated with an increased risk of gonadoblastoma and other gonadal malignancies. However, the indications and optimal timing of prophylactic gonadectomy remain controversial, particularly in asymptomatic individuals, because a subset of TS patients with Y chromosome material may retain residual gonadal function and fertility potential. This study aimed to determine the prevalence of Y chromosome material in TS patients, evaluate the associated risk of gonadal tumors, and assess fertility potential using molecular genetic techniques, thereby providing evidence to inform individualized clinical decision-making. Methods A total of 224 patients with TS diagnosed between 2016 and 2024 were enrolled. Molecular genetic techniques were utilized to identify Y-sequences. In Y-positive cases, we systematically analyzed gonadal tumor incidence via histopathology, endocrine profiles (FSH, LH, AMH), and pelvic imaging findings. Results Y-chromosome material was identified in 11.6% (26/224) of patients. Among the 16 who underwent surgery, gonadal tumors were pathologically confirmed in 4 cases (25.0%), including a tumor in a patient with cryptic Y-material undetected by karyotyping. Importantly, preoperative pelvic ultrasonography failed to detect any definite masses in these tumor-positive cases. Endocrine profiling revealed an age-dependent decline in gonadal function: while prepubertal patients maintained uncertain endocrine activity, those in or beyond puberty exhibited hypergonadotropic hypogonadism. AMH levels indicated that the window for fertility potential is narrow and typically closes by early adolescence. Conclusion TS patients harboring Y-chromosome material face a significant risk of malignancy that cannot be reliably excluded by imaging alone. Our findings reinforce the necessity of early prophylactic gonadectomy. While individualized management may consider fertility preservation in select prepubertal patients, the rapid depletion of ovarian reserve necessitates proactive clinical decision-making.