Frontiers in Endocrinology最新文献

Objective: To study the impact of luteinizing hormone (LH) in stimulation medication on the mature oocyte yield obtained in in women receiving ovarian stimulation (OS) with a dosage of at least 300 IU gonadotropins.

Design: Retrospective cohort study (01/2016-05/2024).

Setting: Tertiary assisted reproductive technology center.

Patients: Women undergoing OS stimulation of at least 300 IU gonadotropins.

Intervention: OS using r-hFSH+r-hLH or HMG as stimulation medication.

Main outcome measure: Retrieved mature oocyte number.

Results: A total of 1,286 patients (696 in the HMG group and 590 in the r-hFSH+r-hLH group) were included in the unmatched cohort. Before matching, the r-hFSH+r-hLH versus HMG-groups showed significant differences in AMH (0.8 vs 1.2ng/mL,p<0.001), starting doses (85.1% vs 70.1% on 450IU,p<0.001), and categorized BMI distribution (p=0.003). After propensity score matching (age, BMI, AMH, basal FSH, starting dose), 1052 cycles were analyzed with a 1:1 match ratio. In the matched cohort after further adjusting for confounders, r-hFSH+r-hLH use was associated with significantly higher collected oocyte count (IRR 1.10, 95% CI 1.03-1.17, p=0.004) and mature oocyte count (IRR 1.12, 95% CI 1.04-1.21, p=0.003) compared to HMG. The sensitivity analysis looking at the interaction of AMH with gonadotropin type showed the effect is mostly significant for those with normal ovarian reserve (AMH between 1.0-3.5ng/mL, IRR: 1.19, 95% CI: 1.07 to 1.33, P = 0.001) but not for those with low (≤1ng/mL, P = 0.180) or high ovarian reserve (>3.5ng/mL, P = 0.932). Analysis of maturation rates showed no significant effect of medication type (p=0.143). The euploid blastocyst count after stimulation in the matched cohort and HMG use was associated with a 22% lower yield compared to r-hFSH+r-hLH (IRR 0.78, 95% CI 0.66-0.93, p=0.006) after adjusting for AMH, basal FSH, female age, dose, body mass index.

Conclusion: The use of r-hFSH+r-hLH is associated with a significantly higher mature oocyte and euploid blastocyst count compared to HMG and the effect was most pronounced in women with normal ovarian reserve.

Introduction: This study aimed to evaluate the diagnostic performance of [⁶⁸Ga]Ga-DOTATATE PET/CT or PET/MR in comparison to dynamic MR (dMR) in locating ACTH-secreting pituitary adenomas in Cushing's disease (CD). The utility of PET and MR semi-quantitative parameters was additionally explored as non-invasive biomarkers for tumor characterization.

Methods: Aretrospective analysis was conducted in 14 patients with CD and 16 controls with ectopic ACTH syndrome. Surgical pathology and post-operative follow-up served as reference standard. All patients underwent [⁶⁸Ga]Ga-DOTATATE PET/CT or PET/MR, dMR; some also underwent [¹⁸F]F-FDG PET. Imaging interpretation included visual and semi-quantitative (SUVmax and ADCmin) assessment.

Results: [⁶⁸Ga]Ga-DOTATATE PET demonstrated a 100% sensitivity indetecting ACTH-secreting pituitary adenomas, superior to dMR with a sensitivity of 85.7%. [¹⁸F]F-FDG PET showed a sensitivity of 80%. Combining [⁶⁸Ga]Ga-DOTATATE PET with functional tests (high dose dexamethasone-suppression test and/or inferior petrosal sinus sampling) achieved specificity up to 100%, whereas the specificity of PET alone was only 50% due to pituitary structural abnormalities. Semi-quantitative analysis confirmed significantly reduced [⁶⁸Ga]Ga-DOTATATE SUVmax and ADCmin in adenomas. Diagnostic efficacy ranked as follows: G-SUVmax from PET/MR was optimal (AUC1.0), followed by ADCmin (AUC 0.96) and G-SUVmax from PET/CT (AUC 0.87).

Discussion: G-SUVmax and ADCmin can be used as reliable diagnostic predictors. [⁶⁸Ga]Ga-DOTATATE PET/MR may facilitate the preoperative localization of CD.

Background: The Gut Microbiome (GM) is now a novel target for the treatment of Type 2 Diabetes Mellitus (T2DM), and several systematic reviews and Meta-analyses have provided evidence on the efficacy and safety of modulating GM in T2DM, but this evidence has not been consolidated.

Objective: The purpose of this scoping review was to summarize the currently available evidence and to assess the breadth and quality of these systematic reviews and Meta-analyses.

Methods: This study was guided by the PRISMA Extension for Scoping Reviews (PRISMA ScR) and the Arksey and O'Malley methodological framework. Electronic searches were conducted in multiple databases from the time of construction to May 1, 2025. Systematic reviews and Meta-analyses of regulatory GM to improve T2DM were included. 2 researchers independently screened full text, extracted review characteristics, and assessed methodological quality using the AMSTAR2 scale tool.

Result: A total of 23 systematic reviews and Meta-analyses were included, which were published in 2015-2024.Probiotics/synbiotics were the most commonly used interventions; the included studies were generally of low methodological quality (only 1 was of high quality); most of the studies reported an improvement in some glycemic and lipid markers by modulating the microbiota, but there was heterogeneity in the results; and there was insufficient attention to adverse events.

Conclusion: The available evidence suggests that regulating GM may be beneficial, but is limited by the quality of the studies, and future studies with large samples, long-term follow-up, and standardized adverse event reporting are needed to demonstrate its safety and long-term effectiveness conclusively.

Systematic review registration: https://doi.org/10.17605/OSF.IO/PW28U.

Objective: Prior to in vitro fertilization (IVF), physicians can choose either recombinant or urine-derived follicle-stimulating hormone (FSH) for ovarian stimulation. The common polymorphism N680S (rs6166) in the follicle-stimulating hormone receptor (FSHR) has been linked to individual variability in ovarian response to FSH stimulation and IVF outcomes, including live birth rates, highlighting its potential value in optimizing stimulation protocols. However, classical genotyping is laborious, often requiring blood as starting material and specialized laboratories for analysis. The aim of the study was to develop a system for rapid and easy-to-use genotyping of the FHSR N680S variant.

Methods: The assay constituted an allele-specific peptide nucleic acid-mediated loop-mediated isothermal amplification (AS PNA-mediated LAMP) assay with a colorimetric detection system. The analytical performance was analyzed with naked-eye detection and verified with fluorescence amplification. Clinical validation was assessed on 50 patients visiting an IVF-clinic in whom the variant was confirmed with Sanger sequencing.

Results: Ninety-one out of 100 samples were genotyped correctly, demonstrating 91% overall accuracy. Clinical sensitivity reached 86.8 [95% Cl 76.4-93.8%], while specificity was 100% [95% Cl 89.1-100%]. The test was performed by trained laboratory staff in less than one hour.

Conclusion: The LAMP assay provides a rapid and user-friendly genotyping of the FSHR N680S, which makes it a valuable tool in point-of-care settings, where it may help guide treatment options prior to IVF.

ENTPD5 and ENTPD6 are members of the CD39-ectonucleoside triphosphate diphosphohydrolase (CD39-ENTPD) family, which play an important role in modulating the purinergic signaling pathway. Most of the knowledge in this area has been obtained by studying CD39/ENTPD1, the prototype member of this family, and evaluating the translational potential by either treating inflammation directly with recombinant proteins or by using antagonists to elicit immune responses in cancer. ENTPD5 and ENTPD6, "orphan-type" ectonucleotidases, are understudied to date, although both are expressed at high levels in various tissues, where they appear involved in regulating signal transduction, cellular energy, and metabolism. ENTPD5 is abnormally overexpressed in several types of malignancies, including prostate, liver, lung, and ovarian cancers. ENTPD5 appears to promote protein glycosylation and folding in part by regulating UDP and UMP levels, thereby enhancing the survival and proliferation of somatic or cancer cells. As such, ENTPD5 has been considered a potential proto-oncogene and a therapeutic target in cancer treatment. In contrast, despite comparable functionality, the related ENTPD6 shows relatively stable expression across tissues in both normal and pathological conditions, with specific roles in cancer yet unclear. This review provides a comprehensive overview of these two understudied ectoenzymes, detailing their shared molecular structures and control of purinergic signal transduction. In addition, we explore different patterns of tissue and organelle expression of these ecto-enzymes and propose relevance to the modulation of cellular metabolism, as would be important in cancer. We review the sometimes conflicting evidence from experimental animal models and propose potential future clinical applications. This review offers insights into the roles of this distinct duo of ENTPD family members to support future basic and translational research in this field.

Diabetic cognitive impairment (DCI) is a frequent complication of diabetes that significantly reduces the quality of life of elderly patients and substantially increases the societal health-care burden. Recent epidemiological investigations have demonstrated that the severity of diabetic retinopathy (DR) is independently associated with a greater risk of cognitive dysfunction. To clarify the relationship between ocular and cerebral comorbidities in diabetes, this paper proposes the diabetic retina-brain axis hypothesis. By reviewing barrier dysfunction, neuroinflammation, and oxidative stress, we systematically present evidence that supports the involvement of the retina-brain axis in DCI and highlight the shared mechanisms that underlie retinal and cerebral damage in diabetes. Therapeutic strategies that target the retina-brain axis, such as hypoglycemic agents, antioxidants and neuroprotective interventions, provide benefits for retinal health and cognitive function. Investigating the mechanisms underlying this axis offers important insights for early diagnosis, prevention and treatment of DCI. Consequently, this research can guide the development of more effective interventions, for example by informing the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors to protect both retinal microvasculature and neuronal integrity. Future research should prioritize elucidating the pathways of information transmission between the retina and the brain, and clarifying the molecular and cellular basis of these processes. This will provide theoretical support for the development of cross-organ collaborative protection strategies.

Objective: This cross-sectional study aimed to elucidate the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and diabetic cardiovascular autonomic neuropathy (DCAN) in patients with type 2 diabetes mellitus (T2DM).

Methods: The study involved patients with T2DM. DCAN was diagnosed using standardized cardiovascular autonomic reflex tests (CARTs) with a total score≥2. MAFLD was defined by the presence of fatty liver disease and T2DM, excluding other liver diseases. The fibrosis-4 (FIB-4) >1.3 indicated a potential risk of fibrosis based on prior studies.

Results: Overall, 30.52% (76/249) patients had DCAN. Patients with MAFLD had a significantly higher prevalence of DCAN than those without (36.49% vs. 21.78%, P=0.013). Univariable analysis revealed a significant association between MAFLD and DCAN (OR = 2.06, 95% CI: 1.16-3.68, P=0.014). This association remained significant even after multivariable adjustment for demographics, diabetes duration, comorbidities (hypertension, diabetic peripheral neuropathy, diabetic retinopathy, metabolic syndrome), and renal function (adjusted OR = 2.76, 95% CI: 1.44-5.29, P=0.002). Among T2DM patients with MAFLD, a high FIB-4 index (>1.3) was independently associated with a substantially increased DCAN risk (adjusted OR = 2.81, 95% CI: 1.19-6.63, P=0.018).

Conclusion: MAFLD is independently associated with a higher prevalence of DCAN in patients with T2DM. The risk was further amplified when high FIB-4 index (FIB-4 >1.3) was present among those with MAFLD. Hence, screening for MAFLD and its associated high FIB-4 levels may help identify patients with T2DM at a higher risk of DCAN.

Objective: Diabetes mellitus (DM) poses a major global public health challenge. Prediabetes, a critical stage in the progression of DM, represents a pivotal window for intervention and prevention. This study aims to develop and validate a machine learning-based prediction model for glycemic reversal in Chinese individuals with prediabetes, with the goal of facilitating such reversal in this population.

Methods: This study analyzed data of Chinese adults from the Dryad database, with a follow-up period from 2010 to 2016. LASSO regression was used to select variables. The selected variables were then used to construct models using random forest, gradient boosting decision tree, eXtreme gradient boosting, Naive Bayes, adaptive boosting, support vector machine (SVM), and Cox model. To assess the discriminative ability of each model, the area under the curve (AUC) was calculated for each. Predictive performance was evaluated by computing time-dependent AUC (t-AUC), accuracy, precision, recall, F1, and C-index. Shapley additive explanations (SHAP) analysis was applied to interpret the key variables identified by the optimal model, and Kaplan-Meier curves for key variables associated with glycemic improvement were plotted to explore differences between groups.

Results: 1792 adults with prediabetes were enrolled. During 5 years of follow-up, 942 achieved normoglycemia, yielding a reversal rate of 52.6%. After differential analysis and LASSO regression screening, 12 feature variables were finally determined for model construction. The 3-year, 4-year, and 5-year AUC values for the Cox model all exceeded 0.61. Six machine learning algorithms were employed to construct predictive models. The SVM demonstrated superior overall performance: it yielded a t-AUC of 0.711, accuracy of 0.652, precision of 0.620, recall of 0.661, F1 of 0.639, and a C-Index of 0.709, outperforming the other algorithms. SHAP analysis revealed that age, FPG, BMI, SBP, DBP, and triglycerides are key factors influencing normoglycemia reversal in individuals with prediabetes.

Conclusion: We developed an SVM model to predict glycemic reversal in the prediabetic population in China, and identified key factors influencing glycemic improvement. This work provides a scientific basis for both this population and clinicians to implement early targeted interventions, thereby aiding in reducing the incidence of DM and alleviating the healthcare burden.

Lymphatic metastasis is a hallmark feature of papillary thyroid carcinoma (PTC), occurring in 30-80% of patients and significantly influencing clinical management. This review comprehensively examines the biological, anatomical, and clinical characteristics of lymphatic spread in PTC, focusing on its diagnostic and therapeutic implications. We detail the molecular mechanisms driving lymphangiogenesis, including the VEGF-C/VEGFR-3 axis and immune-evasion pathways, and highlight the distinct patterns of regional lymph node involvement-from central compartment (Level VI) to lateral (Levels II-V) and rare skip metastases. High-risk clinicopathological features, such as tumor size >2 cm, extrathyroidal extension, and aggressive histological variants, are discussed alongside molecular markers (BRAF V600E, TERT, RET/PTC) that predict metastatic potential. Management strategies are reviewed, balancing the benefits of prophylactic central neck dissection against its risks and emphasizing risk-adapted radioactive iodine therapy. Despite the frequency of lymphatic metastasis, its prognostic impact varies: microscopic nodal disease has minimal effect on survival, while macroscopic or extranodal extension increases recurrence and mortality risks. This synthesis of current evidence aims to guide clinicians in optimizing detection, treatment, and surveillance for PTC patients with lymphatic metastasis.

[This retracts the article DOI: 10.3389/fendo.2025.1606753.].