Artificial intelligence (AI) has advanced rapidly across medicine, and IVF—with its image-rich laboratory workflows, structured cycle data, and measurable endpoints—is among the most amenable fields for integration. Three applications—outcome prediction (T1), stimulation dosing (T2), and radio-frequency identification (RFID) quality tracking (T3)—require no new capital hardware and are immediately deployment-ready, and as professional adoption rose from 24.8% (2022) to 53.2% (2025), the field reached a stratified state of readiness. AI in IVF presents three implementation-relevant findings: the highest-profile technology (embryo selection) is not the most deployment-ready; the lowest-profile (outcome prediction) has the greatest near-term impact; and patients ≥40 years show the largest AI discriminatory advantage. Nine AI technologies (T1–T9) were evaluated across the IVF clinical workflow using four implementation frameworks (TRL/MLTRL, IDEAL, Rogers’ Diffusion of Innovation, NASSS) with OCEBM evidence grading, organized by deployment readiness to derive a deployable toolkit for the 2026 clinic and a synthesis for advanced reproductive age (ARA) patients. Three deployment waves emerged. Wave 1 (≤5 years) comprises outcome prediction (T1), stimulation dosing (T2), and RFID quality tracking (T3), immediately deployable as decision-support adjuncts (12–18 months) pending prospective RCT validation. Wave 2 (5–10 years) comprises AI ultrasound monitoring (T4), sperm analysis and selection (T5), embryo assessment (T6), and endometrial receptivity (T7), positioned for pilot-stage deployment with FDA-cleared FOLLISCAN (T4) leading. Wave 3 (beyond 2031)—miscarriage prediction (T8) and robotic ICSI (T9)—comprises horizon technologies contingent on ethical and engineering resolution. Embryo-selection AUC rises with maternal age from 0.596 (<35 years) to 0.768 (≥43 years; 29% relative increase), positioning ARA patients as candidates for greater AI value pending prospective multicenter validation, while platform-specific findings from the two largest embryo-selection RCTs (LOTUS met endpoint, n=442; iDAScore failed non-inferiority, n=1,066) indicate embryo assessment must be evaluated by platform, not as a uniform category. The three-wave framework lets clinic directors sequence AI investment by readiness; for Wave 1, procurement—not validation—is rate-limiting, and four prerequisite clusters (multicenter RCT completion, regulatory harmonization, ethical frameworks for AI-informed transfer, and workforce/IT infrastructure) must advance in parallel. ARA patients constitute the primary stress test, and ultimately success depends not on algorithmic sophistication but on rigorous validation, governance, and equitable deployment.
Myosteatosis, defined as pathological lipid accumulation within and between skeletal muscle fibers, is increasingly recognized as a determinant of impaired muscle quality, metabolic inflexibility, and adverse clinical outcomes. Although well described in ageing, obesity, and cancer, its relevance to type 1 diabetes (T1D) remains underexplored. T1D is characterized by lifelong insulin deficiency, persistent autoimmune activation, and glycemic variability, conditions that profoundly disrupt cellular energy metabolism and substrate utilization in skeletal muscle, even in the absence of obesity or overt sarcopenia. This review integrates evidence from human imaging, metabolic phenotyping, immunological profiling, and multi-omics analyses to define myosteatosis as an immunometabolic phenotype in T1D. Central to this framework is dysregulation of the AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor (PPAR)-mitochondrial axis, which normally coordinates fatty-acid oxidation, mitochondrial biogenesis, and energy efficiency in skeletal muscle. In T1D, chronic immune activation and metabolic stress suppress AMPK and PPARδ signaling, impair PGC-1α–dependent mitochondrial function, and reduce oxidative capacity, promoting intramyocellular lipid accumulation despite preserved muscle mass. These defects are reinforced by persistent inflammatory signaling (IL-6, TNF-α, IL-1β; NF-κB, JNK, and NLRP3 pathways), accumulation of lipotoxic intermediates (ceramides and diacylglycerols), dysregulated myokine secretion (increased myostatin with reduced IL-15 and irisin), and infiltration of pro-inflammatory macrophages and CD8+ T cells. Mitochondrial stress, reflected by impaired phosphocreatine recovery, altered acylcarnitine profiles, increased oxidative damage, and reduced NAD+–SIRT1/3 activity, further consolidates immunometabolic dysfunction and lipid deposition. Collectively, this review positions myosteatosis as a clinically relevant and potentially modifiable consequence of immune-driven failure of cellular energy utilization in T1D. Because direct mechanistic data from T1D skeletal muscle remain scarce, the framework presented here is deliberately hypothesis-generating: it is assembled substantially by inference from type 2 diabetes (T2D), obesity and ageing models, and we map the resulting evidence gaps explicitly in order to define a research agenda rather than to assert a validated T1D-specific mechanism. Targeting the AMPK-PPAR-mitochondrial axis and its inflammatory and lipotoxic modifiers may enable earlier detection and mechanism-based interventions to preserve muscle metabolic resilience and functional capacity in autoimmune diabetes.
Obesity is a long-term, complex disorder characterised by excessive adiposity that increases the risk of metabolic and cardiovascular diseases. Obesity is a significant health problem, with its prevalence increasing steadily over the last several decades. This rising trend has contributed substantially to the burden of metabolic, cardiovascular and other chronic diseases. Lifestyle modification remains the primary approach to obesity treatment; long-term weight reduction is difficult to achieve and sustain due to complex neurohormonal mechanisms that regulate appetite and energy homeostasis. Consequently, pharmacotherapy has become an essential component of comprehensive obesity management in appropriately selected patients. Recent advances in obesity pharmacology have revolutionised treatment strategies, particularly with the introduction of incretin-based therapies such as glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, which have demonstrated unprecedented efficacy in achieving clinically meaningful and sustained weight loss. Furthermore, several novel agents, including triple agonists, oral peptide formulations, and combination therapies, are currently undergoing clinical evaluation and are expected to further transform obesity treatment. This review provides the current understanding of obesity pharmacotherapy, discusses approved anti-obesity medications, highlights emerging therapeutic agents and drugs under clinical development, and explores future perspectives in obesity management. Additionally, the review addresses current challenges, safety concerns, and public health strategies required to combat the growing obesity epidemic.
ObjectiveThis study aimed to evaluate the safety and efficacy of Ultrasound-guided radiofrequency ablation (US-guided RFA) compared to laparoscopic adrenalectomy (LA) for the treatment of aldosterone-producing adenoma (APA).MethodsThis retrospective, two-center study evaluated 100 patients with APA treated with either US-guided RFA or LA between January 2020 and June 2024. Patients were categorized based on treatment modality (US-guided RFA: n=36; LA: n=64). To minimize confounding, a 1:1 matching was performed based on sex, age, medical history, and disease characteristics. Post-treatment outcomes, including biochemical remission and blood pressure control, were compared using independent-samples t-tests or chi-square tests.ResultsA total of 36 patients (median age: 49.5 years [IQR: 33.25–57.00]; 23 women) underwent US-guided RFA, and 36 matched patients (median age: 52.00 years [IQR: 37.50–59.75]; 20 women) underwent LA. The technical success rate was 100% in both groups. During the follow-up period (median: 14 months [IQR: 6–22 months]), both groups achieved complete biochemical remission (36/36, P = 1.000), similar hypertension control rates (66.7% vs. 77.8%, P = 0.430), and no disease progression (0/36 in both groups). US-guided RFA was associated with significantly lower intraoperative blood loss (median: 3.0 mL vs. 30 mL) and shorter procedure time (77.5 min vs. 115 min; both P < 0.001).ConclusionIn patients with unilateral isolated APA, no significant differences were observed between US-guided RFA and LA in terms of disease progression, biochemical remission, or hypertension control in the short term.
BackgroundPrevious studies have demonstrated that a spongy cement distribution pattern is associated with superior clinical and radiological outcomes in patients with osteoporotic vertebral compression fractures (OVCFs). However, the relationship between MRI-based vertebral bone quality (VBQ) score and spongy cement distribution pattern remains unclear. This study aimed to evaluate the predictive value of the VBQ score for achieving a spongy cement distribution following percutaneous vertebral augmentation (PVA) and to identify independent influencing factors.MethodsWe retrospectively reviewed patients with single-level OVCFs who underwent percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) from January 2020 to December 2024. Patients were divided into spongy distribution group (Spongy group, n=94) and non-spongy distribution group (Non-spongy group, n=142) based on postoperative anteroposterior and lateral X-rays. Potential factors, including age, sex, body mass index (BMI), bone mineral density (BMD), hypertension, diabetes, serum uric acid levels, smoking history, glucocorticoid use, fractured vertebral level, injected cement volume, surgical technique (PVP or PKP), VBQ score, intravertebral vacuum cleft (IVC), vertebral compression ratio (VCR), local cobb angle (LCA), and bone cement leakage, were collected and analyzed. Clinical outcomes, including visual analog scale (VAS) and Oswestry Disability Index (ODI) scores, were recorded and compared between groups at multiple postoperative time points. Complications such as adjacent vertebral fracture (AVF) and bone cement displacement (BCD) were recorded. Logistic regression analysis was performed to identify independent factors associated with the spongy cement distribution pattern. The predictive performance of VBQ score was evaluated by receiver operating characteristic (ROC) curve analysis.ResultsA total of 236 patients were included. Univariate analysis revealed significant differences between the two groups in age, serum uric acid level, VBQ score, BMD T-score, cement volume, presence of IVC, VCR, LCA, and surgical technique (all P < 0.05). Binary logistic regression demonstrated that VBQ score (OR = 0.179, 95% CI 0.053–0.602, P = 0.005), VCR (OR = 0.770, 95% CI 0.677–0.875, P = 0.001), LCA (OR = 0.750, 95% CI 0.667–0.884, P = 0.001), IVC (OR = 0.171, 95% CI 0.045–0.648, P = 0.009), and cement volume (OR = 0.247, 95% CI 0.142–0.430, P = 0.001) were associated with a lower likelihood of achieving a spongy pattern, whereas higher BMD T-score (OR = 6.101, 95% CI 2.097-17.750, P = 0.001) and the PVP (OR = 4.914, 95% CI 1.374-17.574, P = 0.014) surgical technique were associated with a higher likelihood. The VBQ score demonstrated good predictive ability, with an area under the ROC curve (AUC) of 0.759 (95% CI: 0.697-0.821) and an optimal cut-off value of 3.155 (sensitivity: 72.3%, specificity: 73.2%). Patients with spongy cement distribution showed significantly better pain relief and functional improvement, as well as a lower incidence of complications (all P < 0.05).ConclusionThe preoperative VBQ score is a simple, non-invasive, and reliable predictor of spongy cement distribution pattern following PVA in patients with OVCFs. The VBQ score, LCA, VCR, IVC, and higher cement volume were associated with a lower likelihood of achieving a spongy pattern, whereas higher BMD T-score and the PVP technique were associated with a higher likelihood. These findings may assist surgeons in preoperative risk stratification and surgical planning.
Osteosarcoma (OS) is an aggressive primary bone malignancy that predominantly affects children and adolescents. Although surgery and chemotherapy have improved survival, therapeutic progress has remained limited over recent decades. Aberrant fatty acid metabolism has been increasingly implicated in OS progression, yet its distribution across different cellular compartments of the tumor microenvironment remains unclear. In this study, we integrated single-cell RNA-sequencing data from 140,562 cells across 17 OS patients and characterized the metabolic heterogeneity of tumor microenvironment. Two fatty acid metabolism-associated populations were identified: IBSP+ malignant osteosarcoma cells and SPARC+ macrophages. IBSP+ malignant cells showed preferential activation of fatty acid degradation and occupied an intermediate state along the pseudo-time trajectory. Lipid uptake and cholesterol efflux programs reached their highest activity near this state, indicating substantial lipid metabolic remodeling along the inferred transition among malignant-cell states. By contrast, SPARC+ macrophages exhibited a lipid-adapted, immunosuppressive phenotype accompanied by elevated fatty acid degradation activity. Cell–cell communication analysis further identified IBSP+ malignant cells as a major source of APOE- and SPP1-related signals directed toward SPARC+ macrophages, suggesting coordinated metabolic communication between these populations. To evaluate its clinical relevance, we applied transcriptomic deconvolution to independent OS cohorts. Concurrent enrichment of IBSP+ malignant cells and SPARC+ macrophages was associated with significantly shorter overall survival. Comparison of the double-high and double-low groups subsequently identified DKK1 as a candidate effector linked to this adverse metabolic niche. Consistent with this observation, DKK1 silencing in MG-63 cells reduced proliferation, colony formation, migration, and invasion. Collectively, these findings characterize fatty acid metabolism-associated cellular heterogeneity and a clinically relevant association between IBSP+ malignant cells and SPARC+ macrophages in OS, while identifying DKK1 as a candidate prognostic and therapeutic factor associated with the double-high phenotype.
BackgroundTherapeutic adherence is a key component of chronic disease management, particularly in high-risk patients. Type 2 diabetes (T2DM) is common in this population; however, real-world evidence on therapeutic adherence and the factors associated with it among high-risk patients with T2DM remains limited in Spain and other regions.ObjectiveTo evaluate therapeutic adherence and identify factors associated with nonadherence among high-risk patients with T2DM using real-world primary care data.Materials and methodsA cross-sectional study was conducted among adults with T2DM classified as high-risk chronic patients using primary healthcare electronic health records from the Madrid Region as of 30 April 2021. Sociodemographic, functional, clinical, lifestyle, pharmacological, and primary healthcare utilization variables were analyzed according to therapeutic adherence status. Multivariable logistic regression was performed to identify factors independently associated with therapeutic nonadherence.ResultsAmong 67,746 high-risk patients with T2DM, adherence information was available for 65,856 patients, of whom 45,669 (69.3%) were classified as nonadherent. Nonadherent patients had a higher prevalence of polypharmacy (62.1% vs. 58.7%) and greater healthcare utilization, with a higher mean number of primary care contacts during the first year (25.3 vs. 24.4). In the multivariable analysis, the independent factors associated with higher odds of nonadherence were older age (odds ratio (OR = 1.008), male sex (OR = 1.073), foreign status (OR = 1.157), Individual Health Card category 3 (annual income up to €18,000) (OR = 1.245), ischaemic heart disease (OR = 1.137), heart failure (OR = 1.072), COPD (OR = 1.571), asthma (OR = 1.622), depression (OR = 1.054), palliative care (OR = 1.352), smoking status (OR = 1.102), polypharmacy (OR = 1.345), and ≥20 primary care contacts (OR = 1.066).ConclusionsTherapeutic nonadherence is highly prevalent among high-risk patients with T2DM managed in routine primary care. Nonadherence was independently associated with treatment burden, specific patterns of clinical complexity, behavioral factors, and healthcare needs, with some associations showing modest effect sizes, highlighting the multifactorial nature of therapeutic adherence in this population. These findings support the integration of routine adherence assessment and individualized medication management strategies into primary care for patients with complex chronic conditions.
BackgroundNon-obstructive azoospermia (NOA) with meiotic maturation arrest is a severe form of male infertility for which genetic diagnosis may inform counseling and sperm-retrieval expectations.MethodsWhole-exome sequencing was performed in a consanguineous family with NOA, followed by SPDYA variant screening in 31 unrelated NOA patients and 469 men with documented reproductive outcomes. The proband underwent clinical evaluation and microdissection testicular sperm extraction (micro-TESE). Testicular histology, immunofluorescence staining, and meiotic chromosome-spread analysis were used to assess spermatogenic progression. Structural modeling, immunoblotting, co-immunoprecipitation, and exploratory bulk RNA sequencing were performed using testicular material from the proband and a pooled obstructive azoospermia control reference. The three libraries per condition were technical library replicates, not independent biological replicates.ResultsA homozygous SPDYA missense variant (NM_182756.4:c.596G>A; p.R199H) was identified in the proband, and both parents were heterozygous carriers. No additional biallelic deleterious SPDYA variants were detected in the screening cohort. The patient showed NOA, reduced testicular volume, spermatocyte-stage maturation arrest, and failed micro-TESE. Cytological analyses showed absence of post-meiotic germ cells, persistent nuclear γH2AX, failed XY body formation, and no pachytene or diplotene spermatocytes. Structural modeling and co-immunoprecipitation were compatible with weakened SPDYA-CDK2 association, and immunoblotting showed lower apparent abundance of SPDYA, CDK2, and SUN1 in the patient sample. Exploratory transcriptomic profiling showed fold-change-based tissue-level trends consistent with early meiotic arrest and loss of post-meiotic germ-cell programs, rather than direct transcriptional effects of the variant.ConclusionThis single case suggests that biallelic SPDYA variants may be associated with poor sperm retrieval outcomes in severe meiotic arrest, but larger multicenter cohorts are strictly required before SPDYA can be used for clinical prediction or surgical decision-making.
Non-coding RNAs (ncRNAs) are central regulators of epigenomic states, orchestrating chromatin modifications, gene silencing, and nuclear architecture through recruitment of chromatin-modifying complexes. Long noncoding RNAs (lncRNAs) such as XIST, HOTAIR, and MALAT1 exemplify these regulatory roles. Despite their importance, quantitative computational frameworks for linking ncRNA sequence composition to temporal regulatory behaviour remain limited. We introduce a frequency-domain control theory framework modelling RNA sequences as cascaded feedback systems, extending a previously established second-order negative feedback model developed for hormonal endocrine axis dynamics (1,2). This paper constitutes the molecular layer beneath that endocrine framework: where the companion paper characterises the cortisol–HPA axis at the hormonal timescale (τ ≈ 130 min, ultradian period ∼ 90 min), the present work resolves the finer-grained tier of lncRNA-mediated chromatin responses (8–24 min) that constitutes the molecular machinery through which hormonal signals are transduced into epigenetic change. Together, the two frameworks delineate a two-tier frequency hierarchy: the hormonal cascade sets the input signal timescale, and ncRNA sequence composition determines whether the downstream chromatin response is bandwidth-matched to follow it. As a proof-of-concept demonstration using one representative miRNA and one lncRNA sequence, analysis reveals that RNA length and topology encode low-pass temporal filtering properties, with ncRNAs exhibiting slower cutoff frequencies and stronger noise attenuation than short miRNAs. The parameter mapping from sequence composition to control-theoretic parameters is treated as an abstract mathematical heuristic rather than a literal physical law, and the framework is intended to generate experimentally testable hypotheses rather than quantitative physiological predictions. Mixed miRNA–ncRNA cascades show extreme phase accumulation at the stability boundary, a necessary but not sufficient condition for bistable or oscillatory epigenetic regulation. ncRNA sequence composition systematically encodes temporal response characteristics relevant to epigenetic regulation, providing a theoretical basis for predictive modelling of chromatin dynamics and RNA-mediated control systems.
BackgroundThe Leukocyte Glucose Index (LGI) reflects systemic inflammation and glycemic burden and has shown promising predictive value in cardiovascular and metabolic diseases. However, its association with prevalent diabetic retinopathy (DR) remains unclear. We investigated the association and dose–response relationship between LGI and prevalent DR in patients with T2DM and its incremental value beyond traditional clinical factors.Methods1, 727 hospitalized patients with T2DM, including 661 with DR and 1, 066 without DR. Multivariable logistic regression, subgroup, trend, and restricted cubic spline analyses were performed to assess the association between LGI and prevalent DR. Variables selected by LASSO regression and multivariable logistic regression were used to develop a nomogram. Model performance was evaluated by discrimination, calibration, bootstrap internal validation, reclassification metrics, and decision curve analysis (DCA).ResultsHigher LGI was independently associated with prevalent DR (adjusted OR = 1.340, 95% CI: 1.056–1.701, P = 0.016). Similar results were observed per standard deviation increase (adjusted OR = 1.166, 95% CI: 1.029–1.320) and in the highest versus lowest tertile (adjusted OR = 1.378, 95% CI: 1.028–1.848). A positive linear association was identified without evidence of nonlinearity. The nomogram achieved an AUC of 0.727 (95% CI: 0.703–0.752), with an optimism-corrected AUC of 0.719. Although the improvement in AUC after adding LGI was not statistically significant (0.727 vs. 0.725, P = 0.198), NRI and IDI indicated improved discrimination, and DCA showed greater net clinical benefit across a range of threshold probabilities.ConclusionsElevated LGI was independently associated with prevalent DR and showed a positive linear dose–response relationship. LGI may provide incremental discriminative value beyond traditional clinical factors and serve as a simple laboratory marker for identifying prevalent DR. Further external validation and prospective studies are warranted.
ObjectiveTo establish age- and body surface area (BSA)-specific ultrasound percentile charts for thyroid volume (Tvol) in Polish school-aged children born after the introduction of mandatory iodine prophylaxis, and to compare these values with previous national, WHO, and recent European reference data.DesignNationwide cross-sectional analysis of iodine-monitoring data. Methods: The source database contained 10,456 screening records from the National Program for the Elimination of Iodine Deficiency in Poland. After hierarchical exclusions, 3,170 children aged 6–13 years with valid thyroid-volume data were included in the age-specific analysis; 2,843 children with complete anthropometric data were included in analyses requiring BSA. Age- and BSA-specific percentile curves (P3-P97) were generated, and multivariable linear regression was performed to identify independent predictors of Tvol.ResultsMedian urinary iodine concentration (UIC) exceeded 100 µg/L across all age groups, confirming iodine sufficiency at the population level. Median Tvol increased with age from 2.7 to 7.4 mL in girls and from 2.8 to 6.8 mL in boys. The 97th percentile increased from 4.5 to 12.9 mL in girls and from 4.3 to 13.6 mL in boys. BSA was the strongest independent predictor of Tvol, followed by age. Compared with WHO 2004 reference values, the proposed percentiles were consistently higher and closely aligned with recent European data.ConclusionsThis study provides population-specific ultrasound percentile charts for thyroid volume in iodine-sufficient Polish children. These charts complement existing WHO and European references and may improve the interpretation of pediatric thyroid ultrasound in Poland and comparable Central European populations.
With changes in lifestyle and dietary patterns, paediatric hyperuricaemia has become an increasingly recognised metabolic condition worldwide. Its potential implications for skeletal health have attracted growing attention at the intersection of paediatric endocrinology, metabolism, and bone biology. This narrative review synthesises current evidence regarding the potential relationship between hyperuricaemia and skeletal health in children and adolescents. We discuss the epidemiology and clinical characteristics of paediatric hyperuricaemia, potential mechanisms linking urate dysregulation to bone metabolism, and available evidence concerning bone mineral density, bone microstructure, linear growth, and fracture risk. Because direct paediatric evidence remains limited, findings from adult populations, experimental models, and rare inherited metabolic disorders are considered primarily as indirect or hypothesis-generating evidence rather than as definitive proof of causality. We also discuss approaches to skeletal assessment, lifestyle management, and urate-lowering therapy, whilst highlighting major gaps in the current evidence base and priorities for future research.
BackgroundCentral lymph node metastasis (CLNM) occurs in 20–50% of papillary thyroid microcarcinoma (PTMC) patients and influences surgical decision-making. Existing predictive models require complex calculations or specialized tools, limiting clinical utility. This study aimed to develop a simplified risk scoring system for preoperative CLNM prediction using readily available clinical variables.MethodsThis retrospective cohort study included 486 PTMC patients who underwent thyroid surgery with prophylactic central neck dissection between January 2022 and January 2026. Multivariate logistic regression identified independent predictors of CLNM. A simplified risk scoring system was developed by multiplying regression coefficients (β) by 2 and rounding to integers. Internal validation was performed using bootstrap resampling (1000 iterations).ResultsFour independent predictors were identified: male gender (β=0.52, adjusted OR 1.68, 95% CI 1.12–2.53), tumor size >5 mm (β=0.76, adjusted OR 2.14, 95% CI 1.45–3.16), multifocality (β=0.64, adjusted OR 1.89, 95% CI 1.23–2.91), and extrathyroidal extension (β=1.02, adjusted OR 2.76, 95% CI 1.68–4.53). The scoring system assigned 1 point each for male gender and multifocality, and 2 points each for tumor size >5 mm and extrathyroidal extension (total score 0–6). The apparent AUC was 0.742 (95% CI 0.698–0.786), with optimism-corrected AUC of 0.738. Risk stratification demonstrated progressive CLNM rates: very low-risk (score 0, 0%), low-risk (score 1, 22.3%), intermediate-risk (scores 2–3, 34.6%), and high-risk (scores 4–6, 62.2%) (p for trend <0.001).ConclusionsThis simplified four-variable scoring system effectively stratifies CLNM risk in PTMC using preoperatively available data. Patients with score ≤1 may be considered for less extensive surgery or active surveillance, while those with score ≥4 should be considered for prophylactic central neck dissection. This practical tool enables immediate bedside risk assessment without specialized software, though external validation is warranted.
BackgroundThe association between the systemic immune-inflammation index (SII) and diabetic peripheral neuropathy (DPN) remains inconsistent across studies. We investigated the association between SII and prevalent DPN across independent populations and explored complementary biological context using human sural nerve gene-expression data.MethodsWe analyzed a discovery cohort of 555 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999–2000 and performed an exploratory targeted gene-expression analysis of human sural nerve samples from GSE95849. Findings were further evaluated in an independent hospital-based cohort of 400 patients with type 2 diabetes mellitus (T2DM), including 290 with DPN and 110 without DPN. Multivariable logistic regression, component analyses, sensitivity analyses, and restricted cubic spline models were used to evaluate the association between SII and prevalent DPN.ResultsIn NHANES, higher SII was inversely associated with prevalent DPN. Compared with participants in the lowest SII quartile, those in the highest quartile had lower odds of DPN (odds ratio [OR] = 0.239, 95% confidence interval [CI]: 0.102–0.560; P < 0.001). Exploratory targeted analysis of sural nerve tissue showed significantly lower BDNF expression in DPN samples than in samples from patients with diabetes without DPN (BH-adjusted P = 0.0004). JUN expression was also lower in DPN at the nominal level, but the difference did not remain statistically significant after multiple-comparison correction (BH-adjusted P = 0.0686), whereas PDGFRA expression did not differ between groups. In the external cohort, patients with DPN had lower platelet counts than those without DPN (81.6 vs. 135.9 × 109/L; P < 0.001). SII remained inversely associated with prevalent DPN after multivariable adjustment (OR = 0.396 per 100-unit increase, 95% CI: 0.304–0.516; P < 0.001). Restricted cubic spline analysis indicated a significant nonlinear association (P for nonlinearity < 0.001). Among the hematological components examined, platelet count showed the strongest and most consistent association with DPN, whereas the neutrophil-to-lymphocyte ratio (NLR) was no longer significant after mutual adjustment.ConclusionsLower SII was consistently associated with prevalent DPN across two independent populations, with a significant nonlinear relationship observed in the external cohort. Platelet count showed the strongest and most consistent association among the hematological components examined. Exploratory nerve-tissue gene-expression findings provide complementary biological context but do not establish a mechanistic or causal link between platelet-related hematological indices and DPN.
BackgroundUterine artery blood flow resistance is critical for endometrial receptivity and successful implantation. Thyroid autoimmunity (TAI) is prevalent in recurrent pregnancy loss (RPL), but whether TAI affects uterine hemodynamics before conception and whether this predicts subsequent pregnancy outcomes has not been directly investigated.ObjectiveThis study aimed to determine whether TAI is associated with increased uterine artery resistance in non-pregnant women with unexplained RPL (URPL) and whether elevated resistance indices predict adverse subsequent pregnancy outcomes, thereby providing evidence for preconception risk stratification.MethodsA total of 486 non-pregnant women with URPL were enrolled in this retrospective cohort study. Serum TPOAb, TGAb, TSH, FT4 and FT3 were measured. TAI and non-TAI, based on their thyroid antibody status. TAI was defined as TPOAb ≥60IU/mL and/or TGAb ≥60 IU/mL. All underwent transvaginal Doppler ultrasound to measure bilateral uterine artery resistance index (RI), pulsatility index (PI), and peak systolic velocity/end diastolic velocity (S/D). We assessed the incidence of pregnancy, subsequent pregnancy loss, and live birth. Logistic regression analysis was performed to examine the associations between TAI, uterine artery blood flow parameters and subsequent pregnancy loss.ResultsTAI women (n=242) had significantly higher RI, PI and S/D values compared with non-TAI women (n=244) (left RI: 0.82[0.77, 0.85] vs. 0.77 [0.73, 0.83], P <0.001; right RI: 0.82[0.77, 0.85] vs. 0.78 [0.73, 0.84], P <0.001; Right PI: 2.36[2.19, 2.59] vs. 2.29[1.89, 2.56], P = 0.010; Left S/D: 5.56[4.00, 6.25] vs. 4.35[3.70, 5.88], P <0.001; Right S/D: 5.56[4.35, 6.67] vs. 4.55[3.70, 6.25], P <0.001). During follow-up, 240 of 486 women achieved a next pregnancy (49.3%). The clinical pregnancy rate did not differ significantly between the TAI and non-TAI groups (42.6% vs. 48.0%, P = 0.379). Among those who conceived, TAI women had a significantly higher rate of recurrent pregnancy loss (28.7% vs. 16.0%) and a lower live birth rate (71.3% vs. 84.0%) (P = 0.018). Logistic regression showed that TAI positivity (aOR=2.02, 95%CI 1.08-3.87), mean RI (aOR=1.96, 95%CI 1.3-3.00), mean PI (aOR=2.24, 95%CI 1.58-3.30), and mean S/D (aOR=3.567, 95%CI 1.03-1.90) were independent predictors of subsequent pregnancy loss.ConclusionThyroid autoimmunity is associated with increased uterine artery blood flow resistance in non-pregnant URPL women. TAI positivity and elevated uterine artery Doppler indices (mean RI, PI and S/D) were independently associated with subsequent pregnancy loss.
BackgroundOvarian cancer (OV) is a highly lethal gynecological malignant tumor, with a high mortality, low survival rate, and lacking effective biomarkers. The concept of predictive, preventive, and personalized medicine (PPPM) underscores the need for early warning systems and tailored interventions, creating a demand for reliable, stage-specific biomarkers.MethodsA comprehensive proteomic analysis of 60 OV tissues across pathological stages I-IV, and 17 benign ovarian tissues were analyzed with data-independent acquisition (DIA) mass spectrometry. Moreover, these proteomic findings were integrated with TCGA/GTEx data for survival analysis and key molecules, followed by experimental validation with western blot and multiplex immunohistochemistry.ResultsTotally, 1,669 differentially abundant proteins (DAPs) were significantly different in each pathological stage (I, II, III, and IV) of OVs compared to controls. DAPs in the early stage (Stage I-II) were mainly enriched in biological processes related to cell proliferation, such as cell cycle process and chromosome segregation, DAPs in advanced stages (Stages III–IV) were mainly enriched in pathways including extracellular matrix (ECM) organization and cell adhesion. Trend cluster analysis of these DAPs identified six types of trend clusters across different stages of OVs (C1–C6). PPI network analysis identified 28 hub proteins with multiple centrality algorithms. Of them, hub protein SMC2 was localized at nuclear and upregulated during early stage (I/II), which was significantly upregulated at its mRNA and protein levels in OV tissues with TCGA/GTEx, western blotting, and multiplex immunofluorescence analyses, and had a significant relationship with reduced overall survival (HR = 1.31, 95% CI: 1.12–1.55, p = 0.0011) with Kaplan-Meier survival analysis.ConclusionThis study provided the large-scale stage-resolved proteomic atlas of OVs, identifies a 28-protein core module governing cell cycle and genome stability, and reveals SMC2 plays crucial roles in OVs.
IntroductionAcute lymphoblastic leukemia (ALL) is the most common cancer in childhood. With improved survival rates, more attention has turned to long-term outcomes such as bone health. High-resolution peripheral quantitative computed tomography (HR-pQCT) allows a three-dimensional assessment of cortical and trabecular bone and may have advantages over standard dual-energy X-ray absorptiometry (DXA). The aim of this study was to evaluate whether HR-pQCT can detect early bone health impairment in children following ALL treatment.MethodsIn this cross-sectional study, HR-pQCT findings in children within 5 years after completion of ALL therapy were compared with healthy controls. Additional assessments for ALL patients included lumbar spine bone mineral density (LSBMD) assessed by DXA and vertebral fracture (VF) assessment using EOS.ResultsHR-pQCT data from 30 ALL patients (14 male patients; median age 8.8 years) and 64 healthy controls (30 male controls; median age 9.4 years) were analyzed. Five ALL patients (17%) showed evidence of one or more VFs. LSBMD z-scores were within the normal range for all patients (mean 0.09 SDS). Compared with healthy controls, children after ALL treatment showed significantly reduced cortical area (p = 0.013), cortical BMD (p = 0.001), and cortical thickness (p = 0.006) at the tibia, and reduced cortical area (p = 0.046) and cortical BMD (p = 0.008) at the radius on HR-pQCT.ConclusionDespite normal LSBMD DXA z-scores, a substantial proportion of pediatric ALL patients had vertebral fractures and lower values for several cortical parameters at both the radius and tibia on HR-pQCT. These findings suggest that HR-pQCT may serve as a valuable adjunctive tool to detect bone health impairment in children after ALL treatment.
Postoperative recurrence for secondary hyperparathyroidism (SHPT) remains a clinical challenge. Ectopic parathyroid glands are a major cause of recurrence, and those located in the submandibular region are rare. This report retrospectively analyzes three patients on maintenance dialysis who developed recurrent elevation of parathyroid hormone (PTH) levels 3 to 37 months after parathyroidectomy (PTX) for SHPT. Neck ultrasound revealed no definite lesions; however, 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging showed abnormal radioactive tracer uptake in the submandibular region, suggestive of ectopic parathyroid glands. All three patients underwent a second or multiple surgeries, with complete excision of the submandibular masses. Postoperative pathology confirmed parathyroid tissue. After surgery, PTH levels returned to the normal range, and clinical symptoms improved markedly. Combined with a literature review, this article discusses the causes of recurrence after SHPT surgery, the anatomical basis of ectopic lesions in the submandibular region, and the localization diagnosis and treatment strategies for ectopic parathyroid glands, aiming to improve clinical awareness of such rare cases.
ObjectiveThis study aimed to evaluate how insulin sensitivity and secretion defects during mid-pregnancy influence the development of early postpartum glucose intolerance in women diagnosed with gestational diabetes mellitus (GDM).MethodsA total of 1,256 pregnant women diagnosed with GDM between October 2005 and March 2023 were enrolled. Participants were categorized into four groups: GDM-normal, GDM-secretion defect only, GDM-sensitivity defect only, and GDM-mixed defect. Postpartum glucose intolerance was defined as fasting plasma glucose ≥ 100 mg/dL or 2-h plasma glucose ≥ 140 mg/dL during a 75-g oral glucose tolerance test at 6–12 weeks after delivery.ResultsWomen presenting with a sensitivity defect at mid-pregnancy showed a significantly higher rate of postpartum glucose intolerance than those without sensitivity defect (64.9% vs. 46.6%, P < 0.001). Conversely, the presence of a secretion defect alone did not result in a significant difference. The highest prevalence of postpartum glucose intolerance was observed in patients with GDM-mixed defect (GDM-normal 45.7%, GDM-secretion defect only 48.5%, GDM-sensitivity defect only 62.8%, GDM-mixed defect 91.3%; P for trend < 0.001). The risk of postpartum glucose intolerance was 1.46 times higher (95% CI 1.07-2.00) for the GDM-sensitivity defect only group and 5.43 times higher (95% CI 1.20-24.56) for the GDM-mixed defect group, compared with the GDM-normal group.ConclusionsAmong women with GDM, impaired insulin sensitivity identified at mid-pregnancy is associated with a substantially increased risk of early postpartum glucose intolerance, whereas insulin secretion defects are not significantly related to this risk.
IntroductionThis study aimed to examine the relationship between type 1 diabetes mellitus (T1DM) and dental caries among children and adolescents through a meta-analysis, and to assess the potential causal link between these conditions using Mendelian randomization (MR) techniques.MethodsA comprehensive literature review was carried out to identify relevant studies, and meta-analyses were conducted utilizing Stata statistical software. For the MR analyses, summary-level data from genome-wide association studies (GWAS) regarding T1DM and dental caries in childhood and adolescence were gathered.ResultsThe meta-analysis indicated that the decayed, missing, and filled teeth (DMFT) index for permanent teeth was notably higher in children with T1DM compared to the control group, yielding a pooled standardized mean difference (SMD) of 0.19 (95% CI: 0.06–0.31; I2 = 26.6%). However, the MR analysis did not reveal a significant causal relationship between T1DM and the prevalence of dental caries in children and adolescents (OR = 0.98, 95% CI: 0.94–1.02, P = 0.308).DiscussionWhile children and adolescents with T1DM are at an elevated risk for dental caries, no statistically significant causal link was observed.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/177851 identifier CRD2020177851.
