Objectives:This randomised controlled trial assessed the effectiveness and safety of weekly 56.5 μg teriparatide (SAL056) compared to alendronate in postmenopausal women in China with osteoporosis at high risk of fractures over 48 weeks. Methods:This phase 3, multicentre, randomised, open-label, active-controlled, parallel-group, non-inferiority trial enrolled postmenopausal women aged 45-80 years with osteoporosis at 37 centres in China. Participants were randomised (1:1) to receive either subcutaneous teriparatide 56.5 μg weekly or 70 mg oral alendronate weekly for 48 weeks, with the primary efficacy assessment at Week 48. Results:Between November 2021 and September 2023, 493 patients were enrolled (243 in the teriparatide group and 250 in the alendronate group). The primary endpoint, lumbar spine bone mineral density (BMD) at L1-L4, showed a significantly greater increase in the teriparatide group compared to the alendronate group at Week 48 (5.01% vs. 4.20%, mean difference 0.80%, P = 0.025). Sensitivity analysis confirmed these results. At Weeks 24 and 48, teriparatide also resulted in higher hip BMD than alendronate (1.50% vs. 1.46%, P > 0.05 and 3.27% vs. 1.67%, P < 0.001). Procollagen type 1 N-terminal propeptide (P1NP) levels in the teriparatide group increased transiently at Week 12, then declined toward baseline by Weeks 24 and 48, and a decrease in serum cross-linked c-terminal telopeptide of type I collagen (S-CTX) levels from baseline to the end of treatment. Meanwhile, in the alendronate (a typical bone resorption inhibitor) group, CTX level remained continuously suppressed from the baseline. Clinical fracture rates were lower in the teriparatide group than in the alendronate group at Weeks 24 (1.2% vs. 2.8%, P > 0.05) and 48 (1.7% vs. 4.0%, P > 0.05). Teriparatide was generally safe and well tolerated. Conclusions:Teriparatide (56.5 μg once weekly) was more effective than alendronate in treating postmenopausal osteoporosis with a high fracture risk, significantly increasing L1-L4 BMD over 48 weeks. It was safe, well tolerated, and had a safety profile similar to that of Teribone®. The translational potential of this article:This study demonstrates that once-weekly teriparatide significantly improves bone mineral density and reduces fracture risk in postmenopausal osteoporosis patients. As a patient-friendly alternative to daily injections, it may enhance adherence and inform clinical guidelines, representing a promising strategy for patients and healthcare systems.

IntroductionThe artificial pancreas device is an automated control system that simulates the function of the human pancreas. It continuously infuses insulin into the body, thereby maintaining the blood glucose levels of diabetic patients within a safe range. This device is expected to be widely adopted for patients with type 1 diabetes in the future. Currently, research on artificial pancreas control methods is still in its early stages. Most existing blood glucose control methods rely on controller designs that incorporate only gain parameters and typically lack rigorous theoretical analysis of closed-loop system stability. In contrast, the Power Exponent Controller (PEC), which introduces power exponent parameters, belongs to the categories of finite-time or fixed-time control. These controllers often demonstrate superior overall performance in terms of convergence rate, robustness, and other critical control metrics.MethodsThis paper proposes an insulin infusion rate based on PEC. A comprehensive stability analysis of the blood glucose closed-loop system is conducted using backstepping control theory, particularly providing mathematical expressions for system convergence time and steady-state error. The proposed control method is evaluated through three sets of simulation experiments comparing it with a traditional homogeneous control method.ResultsThe theoretical findings suggest that the proposed control method effectively reduces disturbances caused by meals and the infusion process, allowing quick adjustment of the patient's blood glucose to the target range. The results from the three sets of simulation experiments demonstrate that, compared to the traditional homogeneous control method, the proposed PEC scheme offers several advantages: a faster and more responsive reduction in hyperglycemia; the ability to consistently maintain postprandial glucose peaks below 180 mg/dL despite glucose fluctuations caused by three daily meals; and a reduction of approximately 25 minutes in the time required to bring blood glucose into the safe range during extreme daily regulation scenarios involving initial hyperglycemia.DiscussionThese findings indicate that the proposed PEC method provides improved performance for artificial pancreas systems, with potential benefits for clinical management of type 1 diabetes.

IntroductionGraves' disease (GD) is a classical autoimmune disorder caused by interactions between genetic susceptibility and immune dysregulation. However, the transcriptomic mechanisms underlying disease relapse and remission, particularly those involving alternative splicing (AS), remain poorly understood.MethodsWe performed an integrative RNA-seq analysis of peripheral blood samples from 33 GD patients in remission, 31 GD patients in relapse, and 30 normal controls (NC). Gene expression, transcript usage, alternative splicing events (ASEs), RNA-binding protein (RBP) regulation, and splicing quantitative trait loci (sQTLs) were systematically analyzed to characterize transcriptomic alterations associated with different disease states.ResultsCompared with NC, relapse-associated differentially expressed genes (DEGs) were mainly enriched in antimicrobial humoral immunity and suppression of TNF signaling, whereas remission-associated DEGs were associated with metabolic homeostasis and apoptosis regulation. Notably, 74 DEGs were consistently upregulated in both disease states. Transcriptomic analysis identified 234,595 transcripts, including 17.1% novel isoforms, and detected 352 and 387 differentially expressed transcripts (DETs) in relapse and remission, respectively. Transcript-level alterations frequently occurred independently of gene-level expression changes, indicating extensive isoform-specific regulation, as exemplified by isoform switching of HELZ2. In addition, 858 relapse-associated and 670 remission-associated aberrant ASEs (AASEs) were identified. RBP-AASE regulatory network analysis suggested that key RBPs, including APOBEC3C, may contribute to stage-specific splicing remodeling. sQTL analysis further identified 4,507 significant SNP-ASE associations, with affected genes enriched in immune-related pathways, including Th1/Th2/Th17 cell differentiation and TNF signaling. Among these, 12 splicing-related genes also exhibited aberrant AS patterns, while DDX5 and PKM showed sustained upregulation in both relapse and remission phases.DiscussionThese findings demonstrate that GD relapse and remission are closely associated with genetically and RBP-mediated alternative splicing regulation. Our study provides new insights into the molecular mechanisms underlying immune imbalance in GD and highlights potential transcriptomic biomarkers associated with disease relapse.

Eosinophils are correlated with severity of diabetic nephropathy (DN). This study aimed to investigate the causality and molecular mechanisms of eosinophils and DN using Mendelian Randomization (MR) combined with single-cell analysis. The genome-wide association study (GWAS) data for eosinophils and DN were mined from the Integrative Epidemiology Unit (IEU) Open GWAS database and GWAS Catalog database, respectively. GSE30122 and GSE131882 (single-cell datasets) were obtained from the Gene Expression Omnibus (GEO) database. We employed MR to assess causality and conducted sensitivity analysis to evaluate the stability of MR results. By integrating single-cell data analysis, we identified differentially expressed genes (DEGs) and explored their functions and regulatory mechanisms. MR analysis revealed that eosinophils are a risk factor for DN(Inverse variance weighted [IVW], P = 0.025, OR = 1.153). We identified 121 DEGs in GSE30122 and intersected the 153 sc-DEGs of eosinophils in GSE131882, as five key genes were identified: IL7R, CD53, BPTF, FNBP4 and ANKRD36B. Additionally, 11 cell type were identified in GSE131882. Furthermore, in the pseudotime trajectory analysis, lots of eosinophils were consistently observed in the DN group, with key genes highly expressed in the middle and late stages. Enrichment analysis revealed that these key genes were enriched in pathways such as chemokine signaling pathway and oxidative phosphorylation, and multiple microRNAs (e.g., hsa-miR-17-5p) and transcription factors (e.g., GATA2) were predicted. This study showed a causal relationship between eosinophils and DN, and IL7R, CD53, BPTF, FNBP4 and ANKRD36B were identified as five key genes for DN, which may be useful in diagnosis and treatment of DN.

Background: Diabetic kidney disease (DKD) remains a major cause of end-stage renal disease worldwide, yet current clinical biomarkers such as albuminuria and estimated glomerular filtration rate lack sufficient sensitivity to detect early renal injury or predict individual disease trajectories. Growth differentiation factor 15 (GDF15), a stress-inducible cytokine belonging to the transforming growth factor-b superfamily, has emerged as a promising molecular link between metabolic stress, inflammation, mitochondrial dysfunction, and renal injury in diabetes. This review systematically synthesizes current experimental and clinical evidence on the role of GDF15 in DKD, with emphasis on its mechanistic involvement in renal pathophysiology and its translational potential as a biomarker and therapeutic target. Evidence from preclinical models and human studies indicates that GDF15 is upregulated in diabetic kidneys, particularly in tubular epithelial cells, in response to hyperglycemia-induced oxidative stress and mitochondrial dysfunction. Mechanistically, GDF15 modulates key pathogenic pathways in DKD, including NF-kB–mediated inflammation, NLRP3 inflammasome activation, macrophage polarization, TGF-b/Smad-driven fibrogenesis, and autophagy regulation through PI3K/Akt and AMPK signaling. Clinically, circulating and urinary GDF15 levels correlate with disease severity and independently predict renal function decline, suggesting utility in both early diagnosis and prognostic stratification. In addition, emerging evidence supports its potential role as a pharmacodynamic marker responsive to interventions such as metformin and SGLT2 inhibitors. However, its context-dependent biological effects, lack of assay standardization, and confounding elevation in systemic diseases remain key challenges. Overall, GDF15 represents a central stress-integrating mediator in DKD pathogenesis and a promising candidate for precision nephrology, warranting further validation in longitudinal multi-omics and interventional studies.

OBJECTIVES:To investigate whether vitamin D (VD) affects lipid metabolism in granulosa cells in polycystic ovary syndrome (PCOS) through the FABP3-associated PI3K/Akt pathway. METHODS:PCOS rat models were established using letrozole, followed by ovarian transcriptome sequencing, which revealed significant enrichment of lipid metabolism- and PI3K/Akt signaling-related pathways and identified FABP3 as a candidate gene for further investigation. Dehydroepiandrosterone (DHEA)-treated KGN cells were used as a PCOS cell model. FABP3 knockdown/overexpression, VD treatment, and PI3K/Akt inhibition were used to investigate the FABP3-associated PI3K/Akt pathway. Lipid metabolism-related regulators, including FABP3, FASN, ATGL, PPARγ, p-PI3K, and p-Akt, as well as cell viability and proliferation, free fatty acid (FFA) levels, and perilipin-2 expression, were evaluated. In vivo validation in VD-treated PCOS rats and ovarian tissue metabolomics were also performed. RESULTS:Immunohistochemical analysis revealed increased FABP3 and perilipin-2 immunoreactivity in ovarian tissues from PCOS rats. In DHEA-treated KGN cells, DHEA upregulated FABP3, FASN, and PPARγ, downregulated ATGL, inhibited PI3K/Akt phosphorylation, elevated FFA levels and perilipin-2 expression, and reduced cell viability and proliferation. Knockdown of FABP3 largely reversed these DHEA-induced alterations. Similarly, VD treatment alleviated DHEA-induced fatty acid metabolic disorders by decreasing FABP3, FASN, and PPARγ expression, increasing ATGL expression and PI3K/Akt phosphorylation, reducing FFA levels and perilipin-2 expression, and enhancing KGN cell viability and proliferation. The protective effects of VD were abolished by FABP3 overexpression or PI3K/Akt inhibition. In vivo, VD markedly attenuated polycystic ovarian changes and reduced FABP3 and perilipin-2 immunoreactivity in PCOS rats, accompanied by decreased FABP3, FASN, and PPARγ expression and increased ATGL expression and PI3K/Akt phosphorylation in ovarian tissues. Ovarian tissue metabolomics further demonstrated that VD significantly altered lipid metabolite profiles in PCOS. CONCLUSIONS:VD ameliorates lipid metabolic dysregulation in PCOS by modulating the FABP3-associated PI3K/Akt pathway, thereby alleviating granulosa cell dysfunction and ovarian pathological changes.

Adipose stem cell hierarchy was delineated by scRNA-seq analysis, revealing that ICAM-1, a glycoprotein that mediates cell-cell interaction, is a preadipocyte marker. However, the cellular and molecular mechanisms of how ICAM-1+ preadipocytes contribute to adipose tissue homeostasis in vivo remain unclear. To address this, Icam1+/CreERT2 mice were generated, and it was demonstrated that ICAM-1-expressing progenitors actively participated in developing and remodeling white adipose tissue. Under a high-fat diet, both proliferation and adipogenic differentiation of ICAM-1+ preadipocytes increased significantly. Interestingly, ICAM-1 plays a critical role in maintaining the interaction between preadipocytes and immune cells, acting as a checkpoint on white adipogenesis. Mice lacking ICAM-1 specifically in stromal cells exhibited worsened hyperplastic obesity, showing heightened fatty acid synthesis and lipid storage in adipose tissue, and the related insulin resistance. In human adipose tissue, ICAM-1 also marked committed preadipocytes and mediated adhesion between preadipocytes and immune cells. Thus, our study shows that ICAM-1 marks preadipocytes and curbs adipogenesis by facilitating adhesion between preadipocytes and immune cells.

The primary objective of this article is to design a closed-loop homogeneous control algorithm for an artificial pancreas (AP) based on Bergman’s minimal model (BMM), aiming to achieve stable blood glucose regulation in patients with type 1 diabetes while accounting for meal-related disturbances and uncertainties in the insulin infusion process. Although traditional homogeneous control methods offer advantages such as fast response and high accuracy, they do not explicitly analyze the stability of disturbed systems. To address this issue, this study designs a homogeneous blood glucose regulator and proposes an innovative Lyapunov-based stability analysis method for the homogeneous blood glucose control system. Theoretical analysis demonstrates that, when considering uncertainties caused by inter-patient variability, the patient’s blood glucose level can converge to a neighborhood of the reference value. The size of this neighborhood depends on the controller parameters, the dietary glucose content, and the upper bounds of system uncertainties. Furthermore, even in an ideal operating environment for the AP, the insulin subsystem within the blood glucose control system retains finite-time stability properties. Finally, numerical simulations are conducted to validate the theoretical analysis and evaluate the effectiveness of the proposed control algorithm.

The diabetic foot ulcer is among the most serious diabetes-associated complications, with a long disease course considerably increasing the pain and economic burden of patients, leading to amputation and even death. High blood sugar is characteristic of diabetic foot ulcers, with insufficient blood supply, oxidative stress disorder, and high-risk bacterial infection posing great challenges for disease treatment. Advances in hydrogel dressings have shown potential for the management of diabetic foot ulcers involving multisystem lesions. This study comprehensively reviews the pathogenesis of diabetic foot ulcers and advances in hydrogel dressings in treating diabetic foot ulcers, providing innovative perspectives for assessing the nursing care requirements and associated clinical applications.

BackgroundDiabetic peripheral neuropathy (DPN), a common chronic complication of type 2 diabetes mellitus (T2DM), lacks simple biomarkers for early monitoring. This study aimed to explore the association between the ratio of extracellular water to total body water (ECW/TBW) and DPN.MethodsA total of 707 T2DM patients recruited from the Third Affiliated Hospital of Soochow University were included in this cross-sectional study. Multivariate logistic regression analyses were performed to assess the association between the ECW/TBW ratio and DPN after adjusting. Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of the ECW/TBW ratio for DPN.ResultsThe risk of DPN is related significantly with ECW/TBW ratio by multivariate logistic regression analyses, especially the ECW/TBW ratio of arms, trunk, and legs. And the ECW/TBW ratio can not be a indicator to predict the DPN rick of whose BMI is above 28kg/m². Besides, adding the ECW/TBW ratio to the baseline model gained a positive change in the integrated discrimination improvement and continuous net reclassification improvement. The area under the curve (AUC) of ECW/TBW (AUC:0.678) was higher than that of Neutrophil-to-Lymphocyte Ratio (NLR, AUC:0.620) and Platelet-to-Lymphocyte Ratio (PLR, AUC:0.568).ConclusionsThe ratio of ECW/TBW exhibits a potential predictive capacity for DPN and better than NLR and PLR in T2DM patients with BMI <28 kg/m².

BACKGROUND AND AIMS:Osteoporosis, characterized by systemic bone mass reduction and microstructural deterioration, is a growing clinical and economic burden. Type 2 diabetes mellitus (T2DM) has been increasingly linked to poor bone health, elevating the risk of osteoporosis and fragility fractures. The uric acid to high-density lipoprotein cholesterol ratio (UHR) and atherogenic index of plasma (AIP) have emerged as novel metabolic indicators, but their combined role in predicting abnormal bone mineral density (BMD) remains unexplored. This study aims to investigate the individual and combined contributions of UHR and AIP in predicting abnormal BMD in patients with T2DM. METHODS AND RESULTS:This retrospective study included 290 patients with T2DM, recruited from a single center between February 2016 and August 2018. Clinical data, including UHR, AIP, and BMD, were analyzed. Multivariable regression and receiver operating characteristic (ROC) analyses were performed to evaluate the associations between UHR, AIP, and abnormal BMD. Both UHR and AIP were independently associated with abnormal BMD, with stronger associations observed in females and individuals without a history of smoking or drinking. ROC analyses demonstrated modest predictive value for UHR (AUC = 0.5969) and AIP (AUC = 0.6224), with the combined metrics achieving an AUC of 0.6329. CONCLUSIONS:The study highlights that UHR and AIP are negatively associated with total BMD, which can serve as potential predictive markers for abnormal BMD in T2DM patients. A novel clinical prediction model integrating these markers may aid in the early assessment of abnormal BMD risk, facilitating timely preventive interventions.

To investigate the relationship between NSD2 expression in parotid carcinoma tissues and patients’ clinical characteristics, and to explore the effects of siRNA-mediated NSD2 gene knockdown on the proliferation, apoptosis, and invasive capabilities of parotid carcinoma SACC-2 cells. This study included specimens from a total of 59 patients with parotid carcinoma. SACC-2 cells were transfected with NSD2 siRNA. Real-time quantitative PCR was used to detect expression of NSD2 mRNA and western blot was used to detect the expression of NSD2 protein. CCK-8 and colony formation test were used to detect cell proliferation. Annexin V PI double staining flow cytometry was used to detect apoptosis, cell scratch and transwell test were used to detect cell invasion. The apoptosis rates of siNSD2-1 and siNSD2-2 groups were significantly higher. The wounds of siNSD2-1 and siNSD2-2 group were more significant than that of control, and relative migration distances were reduced significantly than that of control (P < 0.05). The cells which penetrated cell membrane of siNSD2-1 and siNSD2-2 were significantly less than those of control (P < 0.05). Silencing NSD2 gene can inhibit the proliferation and invasion of parotid carcinoma SACC-2 cells and induce apoptosis.

Osteoporosis is prevalent among postmenopausal women and is characterized by excessive bone resorption primarily mediated by osteoclasts. This study aimed to investigate the effects of the natural compound Licochalcone D (Lico D) on osteoclast differentiation and its therapeutic potential in ovariectomized (OVX) mouse models of osteoporosis. The cytotoxicity of various doses of Lico D on mouse bone marrow-derived macrophages (BMMs) was evaluated using CCK-8 assays. The differentiation of BMMs into osteoclasts was induced by RANKL treatment, followed by exposure to Lico D at doses of 2, 4, and 8 µg/ml. Additionally, 10 µM BAY 11-7821 (an NF-κB inhibitor) was used to inhibit NF-κB signaling in RANKL-stimulated BMMs. TRAP staining was conducted to measure osteoblast cell number. Western blot analysis was performed to measure protein levels of osteoclast differentiation markers and NF-κB-related factors. RT-qPCR was performed to assess the mRNA levels of downstream genes in the NF-κB pathway. In animal experiments, OVX mice received intraperitoneal injections of Lico D at doses of 10 or 50 mg/kg. Subsequently, femurs were harvested for histopathological examination. Lico D at doses of 2–8 µg/ml showed no significant cytotoxicity toward BMMs. In addition, Lico D inhibited RANKL-induced osteoclast formation and downregulated protein levels of osteoclast-specific genes (mmp9, ctsk, c-Fos and nfatc1). Moreover, Lico D suppressed the phosphorylation of NF-κB p65 and IκBα in RANKL-treated BMMs. Importantly, the suppressive effects of Lico D, especially at 8 µg/ml, on osteoclast cell number and osteoclast-specific markers were comparable to BAY 11-7821. Moreover, Lico D inhibited OVX-induced bone loss and restored dysregulated bone parameters in mice. Lico D inhibits RANKL-induced osteoclast differentiation and alleviates postmenopausal osteoporosis in mice by suppressing the NF-κB signaling pathway.

Thyroid carcinoma (TC) continues to show concerning rates of metastasis and recurrence, despite an overall favorable prognosis. This study aimed to investigate the characteristics and predictive value of synaptotagmin-like 5 (SYTL5) expression and its association with immune infiltration and potential effects on cell apoptosis and proliferation in TC. Messenger ribonucleic acid expression profiles from 45 TC samples and 37 normal samples in The Cancer Genome Atlas database were analysed. The differentially expressed gene SYTL5 was highly expressed in TC tissues and closely associated with the tumour-node-metastasis classification in TC. The receiver operating characteristic curve for predicting TC showed an area under the curve of 0.878. Immune cell expression significantly differed between SYTL5 low- and high-expression groups. Zinc-finger protein 384 (ZNF384) was predicted as the transcription factor of SYTL5 and was found to be underexpressed in TC tissues, showing a negative correlation with SYTL5. Molecular biology experiments demonstrated that SYTL5 expression was elevated in human TC cells and tissues, while SYTL5 knockdown promoted apoptosis and inhibited proliferation in vitro. Zinc-finger protein 384 was shown to bind to the promoter of SYTL5, and overexpression of SYTL5 reversed the effects of ZNF384 overexpression on TC cells. These findings indicate that SYTL5 acts as a potential oncogene in TC and may serve as a biomarker for TC diagnosis. Moreover, this study enhances our understanding of TC's underlying mechanisms and highlights SYTL5 as a promising target for immunotherapy.

Multiple studies have revealed the critical roles of epigenetic modifications in the development of diabetic nephropathy (DN). Methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) RNA modification in podocytes represents a new disease mechanism in DN. The tripartite motif-containing (TRIM) family member TRIM29 was reported to promote podocyte pyroptosis by activating the nuclear factor-κB/NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway. However, whether METTL3-mediated m6A modification of TRIM29 mRNA is involved in podocyte injury remain unknown. Here, we found that METTL3 upregulated the m6A content in mRNA from kidney tissues of mice with streptozotocin-induced DN and in hyperglycemia-induced MPC-5 murine podocytes. METTL3 expression in high glucose-treated MPC-5 cells resulted in elevated release of interleukin (IL)-1β, IL-18, and lactate dehydrogenase and upregulated expression of pyroptosis-associated molecules. Mechanistically, METTL3 was found to directly target TRIM29 for m6A modification and activate TRIM29 transcription. Moreover, the m6A reader YT521-B homology (YTH) domain family member YTHDF1 was recruited by METTL3 to maintain the stability of TRIM29 mRNA, which contributed significantly to increased podocyte pyroptosis. Furthermore, the potent METTL3-specific inhibitor STM2457 prominently alleviated podocyte injury through attenuating activation of the NLRP3 inflammasome/pyroptosis pathway in the DN mouse model. Our results suggest that METTL3 plays a critical role in hyperglycemia-induced podocyte injury through m6A modification of TRIM29 mRNA, which provides new insight for the development of METTL3- and pyroptosis-targeted strategies to treat DN and other diabetic kidney diseases.

To date, monthly oral bisphosphonates have not been available in China. In this randomized, double blind, positive-controlled, multicenter phase III clinical trial, we compared the efficacy and safety of monthly minodronate versus weekly alendronate in the treatment of Chinese postmenopausal women with osteoporosis. A total of 548 participants were screened across 31 study centers, of which 330 participants were randomized into two groups: the experimental group (n = 165) received oral minodronate (50 mg/tablet once every four weeks) and alendronate placebo (once weekly), while the positive control group (n = 165) received oral alendronate (70 mg/tablet once weekly) and minodronate placebo (once every four weeks) for a duration of 48 weeks. The bone mineral density (BMD) of the lumbar spine, femoral neck and total hip were measured using dual-energy X-ray absorptiometry (DXA) at baseline and at 24 and 48 weeks. At the end of treatments, the experimental group exhibited a mean increase (SD) in BMD above the baseline at the lumbar spine, femoral neck and total hip of 4.61% (4.613%), 3.04% (4.034%) and 3.40% (3.569%), respectively, compared with those of 4.55% (3.753%), 1.86% (3.592%) and 2.30% (4.838%) in the control group. All improvements from the baseline in the two groups were statistically significant. The monthly minodronate did not cause new safety risks compared with alendronate. This study demonstrates that monthly minodronate administration is non-inferior to weekly alendronate in terms of therapeutic efficacy, while maintaining a comparable safety profile. Furthermore, the monthly dosing schedule of minodronate may significantly enhance medication adherence among osteoporosis patients, potentially improving long-term treatment outcomes.

OSBPL3 is vital for fatty liver disease, but its immune mechanisms in metabolic dysfunction-associated steatotic liver disease (MASLD) are unclear. This study investigates these mechanisms for MASLD treatment insights. MASLD datasets from public databases were used. OSBPL3 expression was analyzed by t-test in GSE57425, and its function explored via GSEA. Key cell types were identified in GSE129516 by scRNA-seq, followed by cell-to-cell communication and pseudo-temporal analyses. OSBPL3 expression differed significantly between high-fat and normal diet groups (P = .00048). It was enriched in the "oxidative phosphorylation" pathway, hinting at its role in energy metabolism and mitochondrial function in MASLD. Thirteen cell types were identified, with macrophages and monocytes as key types due to expression and cell percentage differences. Macrophages showed closer communication with granulocytes, fibroblasts, and erythrocytes in nonalcoholic steatohepatitis (NASH) diet samples. Macrophage and monocyte differentiation had 9 distinct states, with OSBPL3 highly expressed during metaphase. This study identified macrophages and monocytes as key cell types in OSBPL3's mechanism in MASLD, offering valuable insights for targeted therapies.

MicroRNAs (miRNAs) are pivotal elements to regulate gene expressions, which are thus involved in the progression of a wide range of diseases. In this study, an electrochemical approach is established to detect miR-122 level, which can potentially assist in the diagnosis of non-alcoholic fatty liver disease. A 3D DNA scaffold is first constructed on the surface of the working electrode to improve the reactivity and accessibility. After miR-122 induced intramolecular strand displacement polymerization, the DNA layer is blocked and fails to localize signal strands. The varied electrochemical response is amplified by target recycles due to the quick intramolecular process. This method is highly sensitive and specific. It also effectively differentiates miRNA expression profiles across different clinical samples. The modular design of the DNA probes allows convenient adaptation to other targets, making it a useful tool for miRNA-related studies and clinical applications.

ObjectiveThis study aims to explore the relationship between Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) and arteriosclerosis in type 2 diabetes mellitus (T2DM) patients and to evaluate the mediating effect of blood pressure in this process.MethodsA total of 411 T2DM patients admitted to the Third Affiliated Hospital of Soochow University from January 2021 to December 2023 were selected and divided into the arteriosclerosis group (n = 299) and the non-arteriosclerosis group (n = 112) based on brachial-ankle pulse wave velocity (ba-PWV). General clinical data, metabolic indicators, and sleep-related parameters were collected. The relationship between the apnea-hypopnea index (AHI) and arteriosclerosis was analyzed using univariable and multivariable logistic regression models, while a generalized additive model (GAM) was applied for curve fitting. A segmented regression model was used to explain nonlinearity, and subgroup analysis was conducted to assess interactions. Finally, a mediation effect model evaluated AHI’s direct and indirect effects on arteriosclerosis.ResultsThe AHI of the arteriosclerosis group was significantly higher than that of the non-arteriosclerosis group (P < 0.001). In the unadjusted, partially adjusted, and fully adjusted regression analyses, elevated AHI significantly increased the risk of arteriosclerosis (P < 0.05). Curve fitting indicated a near-linear positive correlation (P = 0.033). The segmented regression model showed that when AHI < 8.8 events/hour, the risk of arteriosclerosis significantly increased with higher AHI (P = 0.008), but the risk increase was not significant when AHI > 8.8 events/hour (P = 0.124). There was no significant interaction between AHI and blood pressure-related index subgroup indicators (P > 0.05). Mediation analysis revealed that systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) had significant mediating effects on the relationship between AHI and arteriosclerosis (P < 0.05), but the direct effect of AHI on arteriosclerosis was not significant (P > 0.05).ConclusionOSAHS severity elevates arteriosclerosis risk in T2DM patients. Blood pressure is a partial intermediary in this effect.