Frontiers in Endocrinology最新文献

Objective: This study aimed to analyze the effect of progesterone (P) levels on the human chorionic gonadotropin (hCG) trigger day and the progesterone on hCG day-to-basal progesterone (P_hCG/P_basal) ratio on pregnancy outcomes in patients with a normal ovarian response undergoing fresh embryo transfer in a gonadotropin-releasing hormone antagonist (GnRH-ant) cycle.

Materials and methods: This was a single-center retrospective study including 1,981 GnRH-ant protocol cycles with fresh embryo transfer from January 2017 to December 2023. All enrolled patients with a normal ovarian response were divided into four groups according to P levels on the hCG trigger day and P_hCG/P_basal ratio based on cutoffs determined by receiver operating characteristic (ROC) analysis: Group A (P level<1.06 ng/mL and P_hCG/P_basal ratio<1.2), Group B (P level <1.06 ng/mL and P_hCG/P_basal ratio≥1.2), Group C (P level≥1.06 ng/mL and P_hCG/P_basal ratio<1.2) and Group D (P level≥1.06 ng/mL and P_hCG/P_basal ratio≥1.2). Subsequently, the associations between clinical variables and pregnancy outcomes were analyzed and compared across the groups.

Results: The positive pregnancy rate (53.5%), clinical pregnancy rate (50.0%), live birth rate (LBR) (43.6%) and singleton rate (36.7%) were significantly higher in Group A than in the other three groups (all P<0.001). Furthermore, the LBR (30.2% vs. 22.4%) and singleton rate (23.8% vs. 17.1%) were significantly higher in Group C than in Group D (both P<0.05). The early miscarriage rate in Group A was comparable to Group B, but lower than in Group C and D (10.6% vs. 14.6% vs. 17.4% vs. 20.4%, P = 0.016). After multivariable logistic regression analysis, the LBR was highest in Group A (Group B vs.A: AOR = 0.437, 95% CI = 0.316-0.603, P<0.001; Group C vs.A: AOR = 0.512, 95% CI = 0.391-0.670, P<0.001; Group D vs.A: AOR = 0.325, 95% CI = 0.240-0.441, P<0.001).

Conclusions: For patients with a normal ovarian response undergoing the GnRH-ant protocol, even a slight elevation in P levels on the hCG trigger day affected LBR. Moreover, the impact of the P_hCG/P_basal ratio on pregnancy outcomes also warrants attention. A serum P level < 1.06 ng/mL on the hCG trigger day and P_hCG/P_basal ratio < 1.2 were associated with a significantly higher LBR. When the P_hCG/P_basal ratio ≥ 1.2, the LBR declined regardless of P levels on hCG trigger day. These findings highlight the potential for incorporating P_hCG/P_basal ratio considerations into individualized clinical management strategies to optimize pregnancy outcomes.

Background: Data on the effects of sacubitril/valsartan combined with dapagliflozin in non-diabetic patients with advanced chronic kidney disease (CKD) are limited. In this study, we evaluated the efficacy and safety of sacubitril/valsartan plus dapagliflozin in non-diabetic patients with advanced CKD.

Methods: A single-center, prospective cohort study was conducted in non-diabetic patients with advanced CKD who had not yet initiated renal replacement therapy. Group A included 65 patients who received combined sacubitril/valsartan and dapagliflozin therapy, while Group B consisted of 59 patients treated with sacubitril/valsartan alone. Estimated glomerular filtration rate (eGFR), proteinuria, blood pressure and serum potassium levels were assessed.

Results: Baseline eGFR was 36.35(31.00, 46.47) and 40.01(30.12, 45.86) mL/min/1.73m² in the Group A and Group B, respectively. There was significant difference in eGFR between the two groups at month 6 [30.92(25.38, 35.38) vs. 25.42(21.58, 30.27)mL/min/1.73m², p < 0.001]. The difference in the change in eGFR between the two groups was statistically significant (p < 0.001). Compared with sacubitril/valsartan alone, the combination of sacubitril/valsartan and dapagliflozin provided an additional significant reduction in blood pressure, attenuated the decline in eGFR, reduced proteinuria, and lowered the risk of hyperkalemia (p < 0.05).

Conclusion: In non-diabetic patients suffering from advanced CKD, treatment with sacubitril/valsartan combined with dapagliflozin effectively controlled blood pressure, reduced proteinuria, slowed the progression of renal dysfunction, and did not increase the risk of adverse events, indicating a favorable safety profile.

Insulin resistance (IR) is a core pathological feature of type 2 diabetes mellitus (T2DM) and is closely associated with mitochondrial dysfunction in insulin-sensitive tissues, including skeletal muscle, liver, and adipose tissue. Mitochondrial abnormalities-such as impaired oxidative phosphorylation (OXPHOS), dysregulated tricarboxylic acid (TCA) cycle, excessive reactive oxygen species (ROS) production, and altered mitochondrial dynamics-can contribute to IR by oxidatively modifying insulin-signaling proteins and activating inflammatory pathways (JNK/NF-κB). Recent work also implicates microRNAs (miRNAs) as modulators that link mitochondrial function and redox balance to insulin action; however, their magnitude and tissue specificity in human T2DM remain to be defined. Therapeutic strategies that target mitochondrial bioenergetics and redox homeostasis show promise, while miRNA-directed approaches are emerging. This review provides an explanatory synthesis aimed at distinguishing associations within the mitochondria-ROS-insulin resistance axis supported by solid evidence from findings influenced by specific contexts, and outlines translational opportunities and their associated delivery bottlenecks.

Background: Few studies have reported the association between intrasellar pressure (ISP) and tumor invasiveness, hypopituitarism, or pituitary apoplexy in patients with pituitary adenomas. This study aimed to investigate the relationship between intraoperatively measured ISP and pituitary adenoma invasiveness, as well as to assess whether elevated ISP is associated with hypopituitarism and pituitary apoplexy.

Methods: We retrospectively analyzed 84 patients with newly diagnosed pituitary adenomas who underwent endoscopic transsphenoidal surgery at the First Affiliated Hospital of Bengbu Medical University between January 2024 and March 2025. ISP was measured intraoperatively. Tumor invasiveness was assessed using the Hardy-Wilson and Knosp grading systems on preoperative MRI. Tumor volume was calculated with 3D-Slicer software. Spearman's correlation analysis was used to evaluate associations between ISP, tumor volume, invasiveness, hypopituitarism, and pituitary apoplexy.

Results: The mean intraoperative ISP was 30.91 ± 7.03 mmHg. Patients with Hardy-Wilson grade III-IV or Knosp grade 3-4 tumors had significantly higher ISP than those with lower grades. Tumor volume correlated positively with ISP, with tumor height showing the strongest correlation. Elevated ISP leads to a higher preoperative incidence of adrenal insufficiency, an increased risk of preoperative hypothyroidism, and a greater likelihood of preoperative hyperprolactinemia in patients with pituitary adenomas, but it shows no clear association with pituitary apoplexy. No significant correlation was observed between ISP and pituitary apoplexy or postoperative hypopituitarism at 12 weeks.

Conclusion: ISP is strongly associated with tumor invasiveness and tumor volume in pituitary adenomas. Elevated ISP increases the risk of preoperative adrenal insufficiency, hypothyroidism, and hyperprolactinemia, but does not appear to affect pituitary apoplexy or postoperative hypopituitarism at 12 weeks.

Background: Growing evidence indicates that thyroid function plays a critical pathophysiological role in diabetic microvascular complications. Nevertheless, the specific association between thyroid hormones, particularly free triiodothyronine (fT3), and diabetic retinopathy (DR) remains controversial.

Methods: After applying the inclusion and exclusion criteria, 3703 patients were included in the baseline analysis. Multivariate logistic regression models were employed to assess the cross-sectional association between baseline fT3 levels and both the prevalence of DR. Subsequently, 1476 patients who underwent follow-up fundus photography were eligible for the retrospective cohort study. This secondary analysis examined the relationship between baseline fT3 quartiles and the risk of DR onset or progression. Additionally, two-sample Mendelian randomization (MR) analysis was performed to analyze the causal effect of circulating fT3 on non-proliferative DR (NPDR) and proliferative DR (PDR).

Results: In the cross-sectional analysis, higher fT3 levels were inversely associated with DR after multivariable adjustment, including NPDR (OR = 0.61, 95% CI: 0.50-0.74) and PDR (OR = 0.24, 95% CI: 0.13-0.44). In the longitudinal cohort, patients with moderate fT3 levels (Q2-Q3) had a lower risk of DR onset or progression versus the lowest quartile (Q1). This protective association remained significant in those with suboptimal glycemic control (HbA1c ≥7%) or longer diabetes duration (≥ 10 years), with risk reductions of 43% (Q2) and 37% (Q3) in the former, and 44% (Q2) and 49% (Q3) in the latter. Notably, among older patients (≥ 55 years), the benefit extended across Q2-Q4. Finally, the MR analysis suggested a potential protective effect of higher fT3 levels on NPDR (MR Egger, OR = 0.131, 95% CI: 0.023-0.755, P = 0.044).

Conclusion: In conclusion, our study demonstrated an inverse association between fT3 levels and the risk of both NPDR and PDR. Moderate fT3 levels were associated with a lower risk of DR onset or progression, particularly among patients with suboptimal glycemic control (HbA1c ≥7%) or longer diabetes duration (≥ 10 years). In older patients (≥ 55years), even relatively higher fT3 levels may be protective. MR analysis suggested a potential protective effect of elevated fT3 levels on the risk of NPDR, which was significant only in the MR Egger model.

Polycystic ovary syndrome (PCOS) ranks among the most widespread endocrine and metabolic conditions affecting women of childbearing age, but its specific pathogenesis remains unknown. More and more evidence indicates that PCOS may be a complex polymorphic disease, influenced by epigenetic and environmental factors, including diet and lifestyle. This review focuses on the role of the gut microbiota and its metabolites in PCOS, a topic that has gained significant attention recently due to the established link between the gut microbiome and metabolic disorders.

Postpartum depression (PPD) significantly impacts both mothers and children, so its early detection is crucial to mitigate these effects. The Edinburgh Postnatal Depression Scale (EPDS) is a widely used screening tool for identifying individuals at risk of PPD. However, PPD symptoms often emerge gradually, and subtle changes in maternal well-being within the low-risk EPDS range may be overlooked. Oxytocin (OT), a neuropeptide important for social functioning and maternal behaviors, may offer deeper insights into the progression of PPD. This exploratory cross-sectional study examined the association between EPDS scores and salivary OT responses to infant-related stimuli in postpartum Japanese mothers without PPD diagnosis. We hypothesized that OT responses would differ according to mothers' EPDS scores, with higher scores associated with blunted OT reactivity. OT responses were assessed within one year postpartum under breastfeeding, interaction, or video tests. Mothers with EPDS <5 showed increased OT responses, whereas those with ≥5 showed diminished responses. The difference in OT responses observed below the EPDS screening cutoff may suggest early biological sensitivity associated with PPD vulnerability. Although the factors determining who develops PPD remain unclear, our findings may highlight the potential value of integrating OT response assessments with EPDS screening to improve early detection. Further, these findings suggest that OT dynamics may serve as a biological indicator of subtle emotional changes during the postpartum period.

Objective: To explore the optimal strategy for streptozotocin (STZ)-induced models of diabetes mellitus (DM) and Diabetic kidney disease (DKD) in C57BL/6J mice, and to analyze potential factors influencing model stability.

Methods: Forty-five 6-week-old male C57BL/6J mice were randomly assigned to six groups: normal control (CON), unilateral nephrectomy control (CU), standard diet with STZ (CS), standard diet with unilateral nephrectomy and STZ (CUS), high-fat diet with STZ (HS), and high-fat diet with unilateral nephrectomy and STZ (HUS). Mice in the HS and HUS groups received a high-fat diet (HFD) for 6 weeks, followed by unilateral nephrectomy (UN) or sham surgery, and were then administered STZ (35 or 45 mg/kg/day, intraperitoneally) for five consecutive days to induce DM. DM induction was confirmed when two consecutive random blood glucose (RBG) measurements were ≥ereu mmol/L. Throughout the study, RBG, body weight, and urine albumin-to-creatinine ratio (UACR) were monitored longitudinally. At 19 weeks post-induction, mice were euthanized for kidney weight assessment and histopathological examination.

Result: All STZ-treated mice initially developed diabetes (100%); however, sustained hyperglycemia was not achieved in all cases. Glycemic stability was strongly influenced by the induction strategy (P<0.05). Specifically, 45 mg/kg/day STZ with a normal diet yielded only a 14.3% remission rate (2/14), whereas 35 mg/kg/day STZ with a HFD resulted in a 62.5% remission rate (10/16). Although 45 mg/kg/day STZ combined with a HFD maintained persistent hyperglycemia, it was accompanied by excessive mortality (80%, 8/10). UN was not associated with glycemic stability (P > 0.05); however, it markedly accelerated DKD progression and exhibited a synergistic effect with HFD. Furthermore, compared with mice exhibiting partial glycemic remission, those with stable hyperglycemia demonstrated significantly higher kidney weight, kidney-to-body weight ratio, and UACR (P<0.05).

Conclusion: An appropriate dose of STZ in combination with UN and HFD represents an optimal strategy for establishing an STZ-induced DKD model in C57BL/6J mice, effectively recapitulating the clinical and pathological features of human DKD and providing a robust platform for mechanistic research and therapeutic development.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic condition in reproductive-aged women, linked to infertility and long-term cardiometabolic risk. Early identification remains challenging because current diagnosis relies on hormone testing and imaging. This research sought to develop and evaluate an interpretable machine learning (ML) model and a simplified nomogram for the early detection of PCOS.

Methods: Data from 1,600 women at the First People's Hospital of Jiashan were used for model training, with 283 external cases from Jiaxing Hospital of Traditional Chinese Medicine for validation. Twenty-three routine laboratory indicators were analyzed. After LASSO feature selection, seven ML algorithms were compared. The best-performing XGBoost model was interpreted using Shapley Additive exPlanations (SHAP). A logistic regression-based nomogram was developed from the key predictors.

Results: The XGBoost model showed excellent discrimination (AUC = 0.919 internal; 0.923 external). SHAP identified DHEAS, AMH, TG, and age as key contributors. The nomogram also performed well (AUC = 0.901 train; 0.887 test).

Conclusions: This interpretable "XGBoost + SHAP" and nomogram framework provides an accurate, transparent, and practical tool for early PCOS screening and individualized management.

It is well-established that individuals with type 2 diabetes mellitus (T2DM) have an increased risk of developing cognitive impairment and dementia, suggesting a close relation between hyperglycemia, insulin resistance, and chronic inflammation. This decline is characterized by a large variety of symptoms going from mild to major form of cognitive impairment characterized of loss of memory, attention, processing speed, and executive function. Preserving the physiological level of glycemia improves cognitive performance, but untreated or inadequately diabetes therapy facilitates the risk of dementia. Some experimental studies have disclosed that drug for diabetes can have protective outcomes on cognitive impairment. In this context, incretin hormone glucagon-like peptide-1 (GLP-1) can reduce blood glucose, improve glucose transport through cell membranes, and to improve brain insulin resistance modulating neuroinflammation. In fact, GLP-1 acts as a neurotransmitter and neuromodulator activating central GLP-1 receptors located in the neurons determining its neurotropic and neuroprotective role in central nervous system. Preclinical and clinical studies suggest the potential role of dipeptidyl peptidase-4 inhibitors (DPP4-i) as therapy for the treatment and prevention of cognitive impairment and dementia. Similarly, several evidences demonstrated that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduces the risk of cognitive impairment and dementia in T2DM patients by improving learning, memory, attention and executive functions. In addition, preclinical studies suggest a possible neuroprotective effect of GLP-1/GIP dual receptor agonist in animal models. The current narrative review, including studies published from September 1987 to September 2025, summarized the recent improvements regarding to the incretin-based therapy for cognitive impairment associated to the type 2 diabetes mellitus.