Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

Objective: To investigate the ability of different concentrations of piceatannol (PIC) solution to biomodify decalcified dentin matrices in primary teeth, thereby providing a theoretical basis for improving the durability of resin-dentin bonding. Methods: This study was approved by the Medical Ethics Committee of the institution. Molecular docking was performed to predict the interaction effects of PIC with type I collagen and matrix metalloproteinases (MMPs) in dentin. A total of 124 clinically extracted intact primary molars were selected due to retention; of these, 76 were prepared into 60 completely decalcified dentin beams and 24 dentin slices. The 60 beams were equally allocated for dry mass loss and swelling ratio testing (30 beams each). For both experiments, the beams were randomly divided into five groups (n = 6): a control group, 5% glutaraldehyde group, and 2.5, 5, and 10 mg/mL PIC solution groups. This was to evaluate the anti-enzymatic hydrolytic properties and mechanical performance of type I collagen. Of the 24 slices, 15 were assigned to the aforementioned five groups (n = 3) for Fourier-transform infrared spectroscopy (FTIR) to explore the cross-linking mechanism. The remaining nine slices were randomly divided into three groups (n = 3): distilled water group A (SEM examination prior to enzymatic hydrolysis), distilled water group B (SEM examination after enzymatic hydrolysis), and a 10 mg/mL PIC solution group (SEM examination after treatment with 10 mg/mL PIC and subsequent enzymatic hydrolysis). This was to evaluate the cross-linking effect on demineralized dentin collagen. The remaining 48 molars were fabricated into bonding specimens and randomly divided into four groups (n = 12): a control group (distilled water group) and 2.5, 5, and 10 mg/mL PIC groups. Immediate and aged shear bond strength (SBS) were measured, and failure modes were observed under a stereomicroscope to investigate the impact of different PIC concentrations on the bonding durability of primary tooth dentin. Results: Molecular docking revealed strong binding activity between PIC and type I collagen/MMPs via hydrogen bonds, electrostatic potential, and hydrophobic forces; the FTIR results confirmed hydrogen bond formation. In the dry mass loss test, mass loss rates in the 2.5, 5, and 10 mg/mL PIC groups were significantly lower than that in the control group (P < 0.05), with the 10 mg/mL PIC group showing the most optimized cross-linking effect. Swelling tests indicated that all three PIC concentrations reduced the swelling ratio of the demineralized matrix, effectively improving its mechanical properties. SEM showed that collagen from the 10 mg/mL PIC group retained its natural three-dimensional network post-enzymolysis, contrasting sharply with the disintegrated collagen in the enzymolyzed distilled water group B but resembling the morphology of the non-enzymolyzed distilled water group A. SBS results demonstrated that the 10 mg/mL PIC group exhibited significantly higher bond strengths than the control group in both the immediate and aged tests (P < 0.05); immediate SBS in the 10 mg/mL PIC group was also significantly greater than that in the 2.5 mg/mL PIC group (P < 0.05), while no other intergroup differences were found (P > 0.05). Failure mode analysis indicated predominantly mixed fractures, with the proportion of interfacial fractures decreasing as PIC concentration increased compared with the control group. Conclusion A 10 mg/mL PIC solution can effectively cross-link decalcified dentin matrices in primary teeth, enhancing the anti-enzymatic hydrolytic capacity and mechanical properties during clinical operation, thereby promoting bond strength and interface stability, which promises to improve the long-term durability of resin-dentin bonding.

ObjectiveTo analyze the potential risk of infection sources during the consolidation phase of schistosomiasis elimination in Lushan County (a mountainous region) of Sichuan Province, and to provide prevention and control strategies for the consolidation of schistosomiasis elimination achievements in mountainous areas. MethodsIn 2024, one to two villages with historically severe epidemics were selected in the heavily endemic townships of Lushan County as monitoring sites to carry out monitoring for wild animal feces, domestic animals, wild rats, free-roaming dogs, local residents, and mobile populations. Follow-up monitoring for previously infected individuals was carried out in Caoping Village of Siyan Town. Statistical analyses were performed to assess the risks associated with infection sources. ResultsA total of 115 fecal samples from 13 species of wildlife were incubated, with all negative. Blood tests were conducted on 492 cattle, 34 sheep, and 261 dogs, with all negative. A total of 2 520 rodent traps were set, capturing 67 wild rats with a capture rate of 2.66%, and no positive wild rats were found upon dissection. The activity track of 25 loose dogs was 2 212 meters at the farthest, 236 meters at the nearest, and 744 meters on average. a total of 68 wild droppings (all dog feces) were picked up along the way, with all negative. Blood tests were performed on 3 540 local population, yielding 39 blood-positive cases with a blood positive rate of 1.1%. Fecal examinations were conducted on 193 individuals, with all negative. A total of 315 blood tests were performed on the mobile population, identifying 1 positive case with a blood-positive rate of 0.32%. One person received a fecal examination, with zero positive. A follow-up survey of 505 previously infected individuals revealed 5 blood-positive cases, with a positive rate of 0.99%. Fecal examinations were conducted on 15 individuals, with all negative. ConclusionIn this investigation, no local or imported sources of schistosomiasis transmission were found. However, there was a wide variety and a large number of potential sources of infection in the local area. It is necessary to actively explore regional monitoring models for schistosomiasis elimination flexibly adjust prevention and control strategies according to local conditions, achieve precise prevention and control, and consolidate the achievements of elimination.

Background and aims Hepatocellular carcinoma (HCC) cells are metabolically reprogrammed for excessive uptake and metabolism of many nutrients. The tumor suppressive microRNA-148a-3p (miR-148a-3p) is downregulated in HCC, whereas its function in regulating HCC cell metabolism remains obscure. Herein we aimed to delineate the role of miR-148a-3p in HCC cell metabolism by using novel bioengineered miR-148a-3p (BioRNALeu/miR-148a-3p) agent produced in vivo. Methods BioRNALeu/miR-148a-3p was designed by using human leucyl transfer RNA fused hsa-pre-miR-34a carrier, overexpressed in Escherichia coli (E. coli), and purified to high homogeneity. After transfection into HCC cells, the released miR-148a-3p levels were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was determined by CellTiter-Glo assays. Targets were validated by dual-luciferase reporter assays, immunoblotting, and immunofluorescence confocal imaging. Glycolysis capacity was evaluated by Seahorse XF assays, and glucose, lactate, and amino acid levels were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Results BioRNALeu/miR-148a-3p was efficiently processed into target miR-148a-3p in HCC cells to effectively inhibit cell proliferation in a dose- and time-dependent manner. Mechanistically, miR-148a-3p suppressed the protein levels of glucose transporter GLUT1/SLC2A1 and L-type amino acid transporter LAT1/SLC7A5 via acting on their 3′-untranslated regions, as well as amino acid transporter ASCT2/SLC1A5. These, in turn, led to a reduction of glucose uptake, lactate production, and glycolytic flux in HCC cells, and alteration of intracellular amino acid metabolome including glutamine, leucine, phenylalanine, tyrosine, and methionine. Conclusions Reintroduction of miR-148a-3p into HCC cells modulates glucose and amino acid metabolism via regulating multiple SLC transporters, thereby suppressing HCC cell viability. These findings highlight the role of miR-148a-3p in HCC cell metabolism and potential of bioengineered miRNA molecules for functional studies and therapeutic development.

Objective To construct a model for predicting the risk of essential hypertension accompanied by left ventricular hypertrophy using machine learning algorithms based on pulse diagram parameters;To explore its clinical application value.Methods A total of 295 patients with essential hypertension who were hospitalized in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai Hospital of Traditional Chinese Medicine and Shanghai Hospital of Integrated Traditional Chinese and Western Medicine were selected from July 2020 to May 2021 and July 2023 to July 2024.According to the echocardiographic results,the selected research subjects were divided into the essential hypertension with left ventricular hypertrophy group(referred to as the"LVH group")and the essential hypertension without left ventricular hypertrophy group(referred to as the"non-LVH group").The general data and clinical biochemical indicators were collected,and the pulse diagram parameters of the patients were detected using the SMART-I type TCM digital pulse analyzer.A clinical prediction model was constructed based on decision tree,support vector machine and extreme gradient boosting model algorithms.The predictive performance of the model was evaluated in terms of discrimination,calibration and clinical prediction ability by using the receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis respectively.The influence of each predictive factor on the risk of LVH in essential hypertension was explained based on the SHAP algorithm.Results Compared with the non-LVH group,the BMI,the proportion of males,drinkers and smokers was lower in the LVH group,with statistical significance(P<0.05);the thickened ventricular wall,left ventricular internal dimension enlargement,left common carotid artery intima-media thickness and high density lipoprotein cholesterol were higher in the LVH group than in the non-LVH group(P<0.05);the left common carotid peak systolic velocity,left common carotid resistance index,serum uric acid and serum creatinine were lower in the LVH group than in the non-LVH group(P<0.05).The pulse diagram parameters T4,T,W1,W2,H3/H1 and H4/H1 were higher in the LVH group than in the non-LVH group(P<0.05).The areas of the ROC curves of the models constructed by the three types of machine learning algorithms were 0.887,0.962 and 0.873 respectively,indicating that the model had good discrimination and certain diagnostic efficacy.The calibration curve suggested that the prediction accuracy of the model was average;the clinical decision curve showed that XGBoost model has a higher net benefit.Conclusion The interpretable model constructed based on pulse diagram parameters and machine learning algorithms can be used as a reliable tool for predicting the risk of essential hypertension with LVH.

Objective:To fine-tune the mT5 (massively multilingual pre-trained text-to-text transformer) large language model, automatically generate report conclusions for teaching purposes from chest CT image descriptions, and assess the quality of automatically generated conclusions.Methods:The training set included 3 000 high-quality physical examination chest CT reports from one hospital, and the external validation set consisted of 600 physical examination chest CT reports from two other hospitals. Experienced radiology teaching physicians assessed the consistency between the generated conclusions and the original physician-written conclusions in the external validation set using a 5-point Likert scale across five linguistic indicators (correctness of examination information, correctness of lesion detection, standardization of terminology, applicability of the conclusions, and simplicity of conclusions). Using the original report conclusions as the reference, the accuracy of the conclusions generated based on the external validation set in describing four major thoracic conditions (pulmonary nodules, pneumonia, emphysema, pleural effusion) was evaluated. Perform chi square test using SPSS 25.0.Results:In the external validation set, the mean consistency score between the generated conclusions and the original conclusions given by the radiology teaching physicians was >4 points, indicating agreement with the original conclusions. In the generated conclusions, the description of the four major thoracic conditions demonstrated 0.95-1.00 (95% CI=0.91-1.00) accuracy, 0.76-1.00 (95% CI=0.59-1.00) sensitivity, and 0.97-1.00 (95% CI=0.91-1.00) specificity. Conclusions:The chest CT report conclusion generation system based on the mT5 large language model demonstrated high accuracy and is expected to provide immediate and efficient automated guidance for standardized residency training.

Objective:To study the risk factors of thyroid nodules in patients with type 2 diabetes.Methods:Data of patients with type 2 diabetes with normal thyroid function admitted to the Department of Endocrinology of Heze Municipal Hospital from January to June 2024 were collected. Binary logistic regression was used to analyze the influencing factors of thyroid nodules in patients with type 2 diabetes, and the receiver operating characteristic curve (ROC curve) was used to evaluate the diagnostic efficacy of each influencing factor.Results:Among 162 patients with type 2 diabetes, 96 had thyroid nodules, accounting for 59.3%. The incidence of thyroid nodules in women was significantly higher than that in men (χ 2 = 4.56, P = 0.034). Multivariate logistic regression analysis showed that age (≥50 years old), overweight and obesity [body mass index (BMI)≥24.0 kg/m 2], high glycated hemoglobin (≥10%), and high total cholesterol ( > 6.5 mmol/L) were independent risk factors for thyroid nodules in patients with type 2 diabetes ( OR = 1.83, 1.67, 1.08, 3.65, P < 0.05), and men was an independent protective factor ( OR = 0.63, P = 0.039). The ROC curve results showed that total cholesterol and total cholesterol combined with glycated hemoglobin could distinguish patients with thyroid nodules from those without thyroid nodules, with AUC = 0.64 and 0.68, respectively, and the differences were statistically significant ( P < 0.05). Conclusions:The incidence of thyroid nodules in patients with type 2 diabetes is relatively high. Age, overweight and obesity, high glycated hemoglobin, and high total cholesterol are independent risk factors for thyroid nodules in patients with type 2 diabetes, and total cholesterol has the ability to distinguish patients with thyroid nodules.

Radiation-induced heart disease(RIHD)is a severe complication in patients with thoracic cancer undergoing radiotherapy,with important impacts on long-term survival among cancer survivors.There is an urgent need to investigate the pathogenesis of RIHD and to develop effective therapeutic agents,and the establishment of high-quality RIHD animal models is pivotal to addressing these issues.This review summarizes the critical factors to consider in establishing RIHD animal models,including species selection,radiation type,dosage,fractionation,and target fields,and modeling timeline,along with the evaluation method and success criteria.We also consider the potential pathogenic mechanisms underlying RIHD,including DNA damage,oxidative stress,inflammatory responses,mitochondrial dysfunction,renin-angiotensin-aldosterone system activation,and myocardial fibrosis,as well as their interrelationships.These insights provide a comprehensive reference framework for constructing RIHD animal models and advancing mechanistic investigations into this condition.

Objective To explore the effects of different concentrations of simvastatin on nerve regeneration after sciatic nerve injury.Methods Rats were randomly divided into the normal group,the control group,the low-dose group and the high-dose group,with 3 rats in each group.Except for the normal group,adult rat sciatic nerve crush injury models were established in the other groups.Rats in the normal group and the control group were orally administered with water,while those in the low-dose group and high-dose group were orally administered with 98%simvastatin at dosages of 4 mg/mL and 40 mg/mL,respectively.The sciatic nerve regeneration in rats was evaluated by sciatic function index(SFI),HE staining,luxol fast blue(LFB)staining and immunofluorescence staining,etc.Results The SFI of rats in the high-dose group 7 days and 14 days after surgery were higher than those in the control group(P<0.05);there was no significant difference in SFI of rats between the low-dose group and the control group 7 days and 14 days after surgery(P>0.05).HE staining and LFB staining results showed that compared with the control group,the number of neurons of rats in the high-dose group increased,the nerve fibers and myelin were clearer and denser,and the nerve function was significantly restored;while no significant improvement was observed in the sciatic nerve of rats in the low-dose group.The immunofluorescence staining results showed that compared with the control group,the immunofluorescence intensity in the high-dose group increased,while that in the low-dose group decreased,the differences were statistically significant(P<0.05).Conclusion High-dose simvastatin can promote peripheral nerve regeneration by regulating the expression of M2 macrophages.