OBJECTIVE: To investigate the predictive value of endothelial activation and stress index (EASIX) for the prognosis of patients with mantle cell lymphoma (MCL). METHODS: A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023, had therapeutic indications and received standard treatment. RESULTS: A total of 66 patients were included and divided into high EASIX group and low EASIX group, according to a cutoff value of 0.97 determined by the receiver operating characteristic (ROC) curve. Multivariate Cox regression analysis showed that prealbumin <0.2 g/L, high EASIX, and ECOG PS score ≥2 were independent risk factors influencing overall survival (OS) in MCL patients. The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months, and the median progression-free survival was 8.8 and 26.0 months, respectively. The proportions of patients with ECOG PS score ≥2 and prealbumin <0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group. CONCLUSION At the time of initial diagnosis, EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL. Furthermore, patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.
Humans ; Lymphoma, Mantle-Cell/pathology* ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; ROC Curve

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

Aim To explore the mechanism of the effect of rosiglitazone(Rsg)on the pancreatic cancer in diabetic mice based on the impact of PPARγ on glu-cose transport and metabolism.Methods A high-fat and high sugar diet combined with STZ was used to construct T2DM model;T2DM mice and normal mice were subcutaneously injected with PANC02 cells to construct a transplanted tumor model.T2DM trans-planted tumor mice and normal transplanted tumor mice were divided into the following groups:Rsg,PPARy inhibitor(PIN-2),rosiglitazone+PPARγ in-hibitor(Rsg+PIN-2),and normal transplanted tumor mice(NDM)and T2DM transplanted tumor mice(DM)were used as control groups,respectively.Tis-sue samples were collected after intervention.Tissue pathological changes were observed by HE staining.The expressions of Ki67 and PCNA proteins were de-tected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.The expression of PPARγwas detected by immunofluorescence.The expressions of Glucokinase,GLUT2,Nkx6.1,PDX-1RT-PCR were determined by Western blot.Results Rsg could significantly reduce the tumor mass,pathological chan-ges,Ki67 and PCNA expression of transplanted tumors(P＜0.05),increase cell apoptosis and the expression of PPARγ,Glucokinase,GLUT2,Nkx6.1,PDX-1 proteins in NDM and DM mice(P＜0.05).PIN-2 could reverse the indicator changes caused by Rsg in NDM and DM mice.However,compared with NDM mice,the above related indicators of the DM group mice were more sensitive to Rsg and PIN-2.Conclu-sions Compared to non-diabetic pancreatic cancer,rosiglitazone can more sensitively inhibit the prolifera-tion of pancreatic cancer with T2DM,induce apopto-sis,and reprogram the metabolism of pancreatic cancer with T2DM by activating PPA Rγ and altering the ex-pression of glucose and lipid metabolism genes,there-by exerting an anti-cancer effect.

Objective: To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). Materials and Methods: We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slope max) and model-based (Ktrans , Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans -10th and Ktrans -mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans -mean and Ktrans -max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans -mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). Conclusion DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and K trans -mean could be promising biomarkers for determining the response to GCs.

Objective: To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). Materials and Methods: We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slope max) and model-based (Ktrans , Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans -10th and Ktrans -mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans -mean and Ktrans -max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans -mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). Conclusion DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and K trans -mean could be promising biomarkers for determining the response to GCs.

Objective: To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). Materials and Methods: We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slope max) and model-based (Ktrans , Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans -10th and Ktrans -mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans -mean and Ktrans -max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans -mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). Conclusion DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and K trans -mean could be promising biomarkers for determining the response to GCs.

Objective: To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). Materials and Methods: We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slope max) and model-based (Ktrans , Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans -10th and Ktrans -mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans -mean and Ktrans -max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans -mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). Conclusion DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and K trans -mean could be promising biomarkers for determining the response to GCs.

Objective: To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). Materials and Methods: We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slope max) and model-based (Ktrans , Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans -10th and Ktrans -mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans -mean and Ktrans -max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans -mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). Conclusion DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and K trans -mean could be promising biomarkers for determining the response to GCs.