Kynurenine pathway (KP) is a major catabolic route of tryptophan, generating a series of bioactive metabolites including kynurenine, kynurenic acid (KA), quinolinic acid, and 3-hydroxykynurenine. Beyond its fundamental role in amino acid metabolism, KP exerts critical regulatory functions in neurodevelopment, synaptic plasticity, and immune modulation. Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with onset in early childhood, characterized by persistent deficits in social communication and restricted, repetitive behaviors. Despite extensive research, the etiological mechanisms underlying ASD remain highly complex and incompletely understood, involving genetic, environmental, and immunological factors. Emerging clinical evidence has consistently revealed a significant imbalance in KP metabolites in individuals with ASD, often accompanied by altered ratios of neuroprotective versus neurotoxic byproducts. However, the primary drivers of this metabolic dysregulation and its causative contribution to ASD pathogenesis are not yet fully elucidated. In this review, we systematically review the enzymatic steps of KP and the principal physiological functions of its major metabolites, with particular emphasis on their dual roles in neuroprotection and neurotoxicity. We then analyze the potential pathogenic mechanisms through which KP dysfunction may contribute to ASD, focusing on two interconnected etiological dimensions. First, KP imbalance can promote oxidative stress, which in turn triggers chronic inflammatory responses via microglial activation and release of pro-inflammatory cytokines, thereby disrupting neuronal homeostasis. Second, aberrant KP metabolism affects neurotransmitter systems, particularly glutamatergic and dopaminergic signaling, leading to impaired neural circuit development and synaptic pruning. By integrating current findings on the KP-ASD association, this review offers a comprehensive etiological framework and a clinically relevant paradigm. Furthermore, we highlight that specific KP metabolites, such as the KA/quinolinic acid ratio, hold promise as peripheral biomarkers for early diagnosis and disease stratification. Finally, we discuss the therapeutic potential of targeting KP enzymes or receptors for personalized intervention strategies, while acknowledging the challenges in translating these findings into clinical practice.

Objective To explore the effects of cerium-doped mesoporous bioactive glass nanoparticles(Ce-MBGNs)as reactive oxy-gen species(ROS)-responsive nanocarriers on inflammation in pulp and their potential to promote odontogenic differentiation of dental pulp stem cells(DPSCs).Methods The cytotoxicity of Ce-MBGNs was assessed by CCK-8.The expression of mRNA of osteogenic/odontogenic differentiation in DPSCs and that of inflammatory factor in RAW264.7 cells were detected by RT-qPCR.Alkaline phospha-tase and Alizarin Red S staining were utilized to investigate their ability to promote dentin mineralization.The ability of Ce-MBGNs to scavenge ROS was evaluated by immunofluorescence and JC-1 staining was used to assess the membrane potential(MMP)of mitochon-drial.Results Ce-MBGNs exhibited good biocompatibility and significantly increased the expression of osteogenic/odontogenic-related genes in DPSCs,promoting mineralization.Additionally,Ce-MBGNs effectively scavenged intracellular ROS,maintained MMP,inhib-ited the expression of pro-inflammatory factors,and promoted the expression of anti-inflammatory factors.Conclusion Ce-MBGNs can protect DPSCs from oxidative damage by maintaining the MMP of mitochondrial and controlling inflammation,and promote their odonto-blastic differentiation,providing a theoretical basis for the development of novel therapeutic agents for oral treatment.

Objective To explore the prediction efficiency of Ki-67 expression status in pituitary adenoma(PA)based on a joint model of siamese network and transfer learning.Methods The preoperative MR T1WI enhanced sequence images of 370 patients with PA diagnosed by surgery and pathology were retrospectively collected.According to the results of immunohistochemical,all patients were divided into high proliferation index group(Ki-67≥3,n=97)and low proliferation index group(Ki-67＜3,n=273),and all the sample data were randomly divided into training set and test set according to the ratio of 7∶3.Two single predictive models,ResNet-50 and VGGNet-16 and combined them with the siamese network and transfer learning were built.The prediction efficiency of different models were evaluated via accuracy rate,precision rate,recall rate,F1 score and receiver operating characteristic(ROC)curve as the main criteria.Results Compared with a single predictive model,the model combined with siamese network and transfer learning showed a better performance for predicting the Ki-67 of PA.Additionally,the ResNet-50 joint model exhibited the superior predictive performance.The accuracy rate was 0.872 7,the precision rate was 0.812 5,the recall rate was 0.764 7,the F1 score was 0.787 9,and the area under the curve(AUC)was 0.841 6.Conclusion The joint model based on siamese network and transfer learning exhibits a higher efficiency for predicting the Ki-67 expression status in PA,which can help the clinicians to formulate more personalized treatment for the patients.

Objective To investigate the effects of human milk on serum bilirubin levels and gut microbiota in neonatal rats with hyperbilirubinemia.Methods A total of 24 7-day-old specific-pathogen-free Sprague-Dawley rats were injected with bilirubin or normal saline,respectively,and human milk or formula milk was administered 24 hours later for intervention.The rats were divided randomly into four groups:human milk-normal saline group(HN),human milk-bilirubin group(HB),formula milk-normal saline group(FN),and formula milk-bilirubin group(FB).Samples were taken 72 hours later,and serum bilirubin values were detected by enzyme-linked immunosorbent assay.The intestinal microbiota were analyzed using 16S rDNA high-throughput sequencing.Results There was no significant difference in bilirubin values among the groups.Pseudomonas was negatively correlated with indirect bilirubin value(P＜0.05).The composition of the intestinal microbiota differed significantly between human milk and formula milk after gastric administration,with Firmicutes(P＜0.01),Enterococci(P＜0.05),being the main microbiota in the HN and HB groups,and Proteobacteria(P＜0.001),Escherichia Shigella(P＜0.01)and Acinetobacter(P＜0.01)being the main in the FN and FB groups.Conclusions Pseudomonas may be negatively associated with bilirubin,and the structure of the intestinal microbiota may differ in relation to human milk and formula feeding.

Objective:To evaluate the value of multi-slice spiral CT (MSCT) in the diagnosis of liver metastases with rich blood supply.Methods:The clinical data and imaging data of 19 patients with liver metastases with rich blood supply admitted to the 921st Hospital of the Joint Logistics Support Force of Chinese People′s Liberation Army from September 2018 to September 2023 were retrospectively analyzed, and the number, location, shape, size of the lesions and the images of CT plain scan and dynamic enhanced scan were analyzed.Results:Among the 19 patients, there were 18 multiple cases and 1 single case. A total of 108 lesions were found. There were 62 cases (57.4%) in the right lobe of liver and 87 cases (80.6%) in the peripheral part of liver. The form of circular or quasi-circular, there were 99, irregular shape or lobed 9. The focal diameter was 0.6-6.8 cm. CT plain scan showed that 99 lesions showed slightly low density, and the other 9 lesions showed equal density relative to the background liver. In the dynamic enhanced scan, 108 lesions in arterial stage showed high-density enhancement, 97 lesions showed circular enhancement, and 11 lesions showed nodular enhancement. Among them, 77 lesions had moderate to obvious intensification density. Of the 108 lesions in the portal vein stage, 31 lesions showed moderate to obvious enhancement density, 49 lesions showed slightly low clearance density, and 28 lesions showed continuous enhancement density. In the delayed stage, all 108 lesions showed slightly low density.Conclusions:The main features of liver metastases with rich blood supply are: low density on plain CT scan, annular or nodular enhancement in the arterial phase of enhanced CT scan, and the peak of enhanced density can be in the arterial phase or the portal vein phase. Combined with clinical data, CT can make a correct diagnosis.

Objective:To investigate the effects of short-term olfactory training and visual stimulation on olfactory recognition function and quality of life in patients following functional endoscopic sinus surgery (FESS).Methods:A total of 80 patients who underwent FESS in the Department of Otorhinolaryngology Head and Neck Surgery at the Affiliated Hospital of Xuzhou Medical University between December 2023 and February 2024 were enrolled in this study. The cohort comprised 67 males and 13 females, aged from 17 to 75 years. Participants were randomly allocated to either a control group ( n=40) or an experimental group ( n=40). The participants in control group received routine postoperative management, including nasal irrigation, oral antibiotics and glucocorticoids, topical budesonide nasal spray, and hypertonic saline solution for 12 weeks. In addition to the standard care, the participants in experimental group underwent olfactory-visual stimulation training starting 24 hours postoperatively, lasting for 2 weeks. The olfactory identification test (OIT), visual analogue scale (VAS) for olfaction and Questionnaire of Olfactory Disorders of Life (QOD-QoL, hereafter referred to as QOD) were administered preoperatively. Follow-up assessments were performed 2 weeks and 3 months postoperatively, with the same tests repeated. Data were analyzed using SPSS 27.0 and GraphPad Prism 7 statistical software. Results:There was no significant difference in preoperative OIT, VAS, and QOD scores between the two groups. The olfactory recognition function of some patients was improved after removing the packing material 24 hours after FESS surgery. The OIT scores of 2 weeks post-surgery were significantly higher than preoperative values in both groups (the experimental group Z=-4.73, P<0.001; the control group Z=-4.73, P<0.001). Participants in both groups showed improvements in olfactory VAS and QOD scores (experimental group Z value was -2.88 and -5.45, P<0.01 and<0.001, respectively; the control group Z value was -4.42 and -5.50, respectively, both P<0.001). However, there was no significant difference in the VAS score between the two groups ( Z=-0.68, P=0.499). The paticipants in experimental group showed greater improvement in OIT and greater reduction in QOD scores compared to the control group ( Z=-2.19, P=0.029; Z=-2.99, P=0.003). There was no significant difference in the decrease of olfactory VAS between the two groups ( Z=-0.02, P=0.988). There were no statistically significant differences of all patients in VAS, OIT and QOD scores at 2 weeks and 3 months after surgery (experimental group Z value was -0.91, -0.90 and -1.43, respectively, all P>0.05; control group Z value was -1.21, -0.84 and -0.91, respectively, all P>0.05). At 3 months post-surgery, the OIT scores in the experimental group were higher, the QOD scores were lower than those in the control group ( Z=-2.89, P=0.004; Z=-2.87, P=0.004). Conclusion:Short-term olfactory-visual stimulation training in the early postoperative period of FESS significantly improves the olfactory recognition function and enhances the quality of life of patients.

Objective:To investigate the correlation between frailty and immune markers in elderly patients diagnosed with heart failure with preserved ejection fraction(HFpEF).Methods:A total of 416 elderly patients with HFpEF, who were hospitalized in the Department of Geriatrics at Henan Provincial People's Hospital from March 2021 to December 2023, were selected as research subjects.The Fried frailty phenotype was employed to assess frailty.Fasting venous blood samples were collected to measure levels of CD4+ T lymphocytes, CD8+ T lymphocytes, the CD4+ /CD8+ ratio, and immunoglobulins A, M, and G. Spearman correlation analysis and multiple linear regression analysis were conducted to evaluate the relationship between frailty scores and immune markers.Results:Spearman correlation analysis revealed a significant association between frailty score and the CD4+ /CD8+ ratio( r=-0.659, P<0.001), immunoglobulin A( r=-0.454, P<0.001), immunoglobulin M( r=-0.522, P<0.001), and immunoglobulin G( r=-0.802, P<0.001).Furthermore, multiple linear regression analysis indicated that, after adjusting for confounding factors, frailty score served as a significant negative predictor of the CD4+ /CD8+ ratio( β=-0.562, P<0.001), immunoglobulin A( β=-0.366, P<0.001), immunoglobulin M( β=-0.445, P<0.001), and immunoglobulin G( β=-0.772, P<0.001).In comparison to the non-frail group, the frail group exhibited significantly lower values for the CD4+ /CD8+ ratio( β=-0.666, P<0.001)and levels of immunoglobulin A( β=-0.514, P<0.001), immunoglobulin M( β=-0.526, P<0.001), and immunoglobulin G( β=-0.814, P<0.001). Conclusions:In hospitalized elderly patients with heart failure with HFpEF, frailty serves as an independent risk factor for the reduction of the CD4+ /CD8+ ratio, as well as levels of immunoglobulin A, immunoglobulin M, and immunoglobulin G. Furthermore, the frailty score demonstrates a significant negative predictive value for these immunological markers.Therefore, it is essential to enhance our understanding of frailty and to prioritize its prevention and treatment, as this may help mitigate immune dysfunction and promote recovery in elderly patients.

Nature killer(NK)cells are lymphocytes of the innate immune that play a significant role in aging through direct cell killing and secretion of cytokines.NK cells can delay the occurrence of age-related diseases and prolong lifespan by eliminating senescencent cells.Significant progress has been achieved in the research utilizing NK cells to improve aging.This review aims to summarize that the recent research on the mechanism of NK cells in the context of senescence, as well as the progress made in anti-senescence interventions through animal and clinical studies.Nevertheless, substantial challenges remain for the clinical application of NK cell-based anti-senescence therapies.

Objective:To compare the differences of three-dimensional computed tomography(3DCT),four-dimensional computed tomography(4DCT),and multi-parametric magnetic resonance(MR)sequences of the radiotherapy for liver cancer in delineation for target area,and analyze which MR sequence was more accurate in assisting CT image to delineate the target area,and design respectively reverse intensity modulated radiotherapy plan,and compare the dosimetric parameters of the target areas of receiving radiotherapy and normal liver tissue.Methods:This retrospective study was conducted to analyze radiotherapy data from case data of 18 patients with hepatocellular carcinoma(HCC)who admitted to the First Affiliated Hospital of Bengbu Medical University between August 2023 and June 2024.These data included 10 respiratory phases in 3DCT and 4DCT,and free-breathing sequence(MR-FB),diaphragm navigation sequence(MR-NAVI),and breath-hold(MR-BH)sequence of multi-parametric MRI,and the gross tumor volumes(GTVs)of them were delineated,which were respectively 5 modal images and liver contours included GTV3D,GTV4D,GTVMR-FB,GTVMR-NAVI,and GTVMR-BH.Pinnacle3 9.8 treatment plan system(TPS)was applied to conduct registration and fusion for image by using mutual information method.The 3DCT(GTV3D)was used as reference image to compare the volume of target area,and the displacement of mass center with other 4 kinds of images.The volume difference(VD),overlap ratio(OR),Dice similarity coefficient(DSC),and Jaccard index(JAC)were used to assess the differences among different target area.The indicators of plan evaluation included conformity index(CI),homogeneity index(HI),GTV doses(D2%,D98%,Dmean),and the exposure dose of normal tissue of liver.Results:In images of five modalities,the GTV median volumes were respectively 28.83,33.10,26.75,25.05,and 22.65 cm3.In images of five modalities,the median volume of liver were respectively 1293.46,1483.09,1213.81,1195.69,and 1141.02 cm3.Compared with other 3 target areas,the displacement of GTVMR-BH was the smallest on head-foot direction,with statistically significant differences among them(Z=-2.305,-2.307,-2.134,P<0.05).The OR,DSC,and JAC values of GTV4D were significantly better than these of GTVMR-FB,GTVMR-NAVI,and GTVMR-BH(ZOR=-2.911,-3.006,-3.195,ZDSC=-2.726,-2.215,-2.556,ZJAC=-2.556,-2.704,-2.953,P<0.05).The VD value of GTVMR-FB was better than that of GTV4D,GTVMR-NAVI,and GTVMR-BH,with statistically significant(Z=-2.675,-2.817,-2.580,P<0.05).Additionally,the OR,DSC,and JAC values of GTVMR-FB and GTVMR-NAVI were better than those of GTVMR-BH,with statistically significant(ZOR=-2.859,-2.817,ZDSC=-2.184,-2.783,ZJAC=-2.385,-2.783,P<0.05).All five plans met clinical dose requirements.Friedman test showed there was no statistically significant differences in dosimetric parameters of target area among different plans(P>0.05).However,compared to the PTV3D plan,the PTVMR-FB,PTVMR-NAVI,and PTVMR-BH plans resulted in lower levels in mean dose(Dmean)of liver and volume parameters(V5,V10,V20,V30)of various doses,with statistically significant differences(Dmean:Z=-2.433,-2.307,-2.807,ZV5=-2.512,-2.433,-2.652,ZV10=-2.433,-2.536,-2.968,ZV20=-2.536,-2.652,-2.807,ZV30=-2.611,-2.652,-2.968,P<0.05).Conclusion:In actually clinical application,MR-NAVI and 4DCT also can be adopted to assist 3DCT to delineate target area besides MR-FB sequence that is conventionally used in MR location,thus can enhance precision of delineation,and optimize radiotherapy plan,and decrease exposure dose of normal liver tissue.