Tumor is the result of long-term and unlimited proliferation of cells. Tumor cells adjust various metabolic fluxes to meet increased bioenergy and biosynthetic requirements. Serine is one of the eight non-essential amino acids in the human body. It plays an important role in a variety of physiological activities and can provide one carbon unit, glycine, etc. for cell proliferation. Serine hydroxymethyltransferase (SHMT) is a key enzyme that catalyzes the conversion of glycine and serine. It is highly expressed in a variety of tumors and is a potential target for anti-tumor drugs. This article focuses on the potential of SHMT as a new target for cancer treatment and the preliminary application of its inhibitors in preclinical studies of tumors, providing reference for the development of new targeted drugs for tumors.

Salvia miltiorrhiza (S. miltiorrhiza) represents a crucial component of traditional Chinese medicine, demonstrating effects on blood circulation activation and stasis removal, and has been widely utilized in asthma treatment. This study isolated a novel phenolic acid (S1) from S. miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time. An allergic asthma (AA) model was established using ovalbumin (OVA). The mechanism of S1's effects on AA was investigated using multi-factor joint analysis, flow cytometry, and co-culture systems to facilitate clinical asthma treatment. S1 (10 or 20 mg·kg^-1) was administered daily to mice with OVA-induced AA (OVA-AA) during days 21-25. The study examined airway responsiveness, lung damage, inflammation, and levels of immunoglobulin E (IgE), PGD2, interleukins (IL-4, 5, 10, 13, 17A), tumor necrosis factor α (TNF-α), GM-CSF, CXCL1, CCL11, and mMCP-1. Additionally, mast cell (MC) activation and degranulation were explored, along with T helper type 17 (Th17)/Treg immune cells and TLR4 pathway biomarkers. The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 µmol·L^-1), a specific TLR4 blocker, against S1 (10 µmol·L^-1) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 µg·mL^-1) to elucidate the TLR4 pathway's mediating role. S1 demonstrated reduced airway responsiveness, lung damage, and inflammation, with downregulation of IgE, PGD2, interleukins, TNF-α, GM-CSF, CXCL1, CCL11, and mMCP-1. It also impeded MC activation and degranulation, upregulated IL-10, and influenced Th17/Treg immune cell transformation following OVA challenge. Furthermore, S1 inhibited the TLR4 pathway in OVA-AA mice, and TLR4 antagonism enhanced S1's positive effects. Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms, restores lung function, and inhibits airway response. S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.

OBJECTIVE To construct a predictive model for timely medication retrieval of outpatients， accurately identify high-risk patients with delayed medication retrieval， and provide data support for the development of differentiated registration strategies and resource optimization allocation in smart pharmacies. METHODS Based on 680 568 valid outpatient prescription records from January to March 2025 at the First Affiliated Hospital of Xi’an Jiaotong University， a dual-clustering analysis was conducted using K-means algorithm and Gaussian mixture model （GMM）. An adaptive threshold for medication retrieval time difference was determined by combining contour coefficients， and “timely medication retrieval” and “delayed medication retrieval” were divided to construct binary objective variables； six types of features were screened through a multi-method fusion strategy； the performance of 6 kinds of base learners and 4 kinds of ensemble learning models were evaluated from three dimensions： discrimination， overall performance， and calibration， and explanatory analysis of the models were conducted. RESULTS The results of the dual-clustering analysis showed that the silhouette coefficient of GMM was better than K-means （0.702 4 vs. 0.698 8）， and the final adaptive threshold was determined to be 49.82 min. Among the prescriptions included， 74.99% were for timely medication retrieval and 25.01% were for delayed medication retrieval. Among the 10 candidate models， the Stacking model performed the best， with an area under the test set curve of 0.954 4， F1 score of 0.942 4， accuracy of 0.911 5， Brier score of 0.066， and good discrimination and calibration. The explanatory analysis results of the model showed that its predictions were driven by multiple factors such as patient historical behavior， and diagnostic related characteristics. CONCLUSION This study constructed a timely medication retrieval prediction model for outpatients based on a two-stage adaptive threshold ensemble learning algorithm， which has high accuracy and stability， and can achieve dynamic judgment of patient medication retrieval behavior.

Temporal lobe epilepsy(TLE)is the most common form of focal epilepsy in adults,characterized by spontaneous recurrent seizures,with most patients experiencing drug resistance and cognitive dysfunction.MicroRNAs(miRNAs)play a critical role in the pathological process of TLE through their regulation of post-transcriptional gene expression.The pathogenesis of TLE has not been fully elucidated,lacking effective clinical therapeutic targets and prognostic markers.This review sum-marized the expression changes of miRNAs in TLE and their research progress as potential biomarkers,aiming to provide new insights into the early diagnosis,prognosis evaluation,and pathogenic mecha-nisms of TLE.

Objective To explore the effect of compound active tea of Lithocarpus litseifolius on uric acid levels and kidney function of mice with hyperuricemia nephropathy and to provide an experimental basis for the development of hyperuricemia nephropathy drugs and functional food.Methods A mouse model of hyperuricemia nephropathy was established by administering potassium oxazinate with adenine.Mice were randomly divided into common,model,positive drug(10 mg/(kg·d))and compound active tea of Lithocarpus litseifolius high-,middle-and low-dose groups(10 g/(kg ·d),3.33 g/(kg·d)and 1.11g/(kg·d),respectively).One hour after the last gavage,urine protein(UP)was measured by CBB method,urea nitrogen(UUN)was measured by urease method.Orbital blood pampling,blood was collected for uric acid(UA)analysis by enzyme ratio method,urea nitrogen(BUN)was measured by urease method.The serum contents of interleukin 6(IL-6)and tumor necrosis factor(TNF-α)were measured by ELISA.Take kidney tissue,levels of urate transporter 1(URAT1)and glucose transporter 9(GLUT9)were measured by quantitative fluorescence,kidney histopathological changes were observed by HE stainning.Results Compared with the control group,the model group's levels of UP,UUN,UA,BUN,IL-6,URAT1,ULUT9 and TNF-α were significantly increased(P＜0.01,P＜0.05),and the renal tissue structure was normal.Compared with the model group,the positive group's levels of UP,UUN,UA,BUN,IL-6 and TNF-α were significantly decreased(P＜0.01,P＜0.05),there was little glomerular atrophy or deformation in the kidneys,kidney tubular dilatation was occasionally seen,but there was no inflammatory cell infiltration.Compared with the model group,the high-dose compound active tea of Lithocarpus litseifolius group's UP,UUN,UA,BUN,IL-6,URAT1,TNF-α and GLUT9 levels were significantly decreased(P＜0.01,P＜0.05).The middle-dose compound active tea of Lithocarpus litseifolius group's UP,UUN,UA content,IL-6,URAT 1,GLUT9,BUN and TNF-αwere significantly decreased(P＜0.01,P＜0.05).The low-dose compound active tea of Lithocarpus litseifolius group's UP,UUN,UA,IL-6,URAT1,BUN,TNF-α and GLUT9 levels were significantly decreased(P＜0.01,P＜0.05).Conclusions Compound active tea of Lithocarpus litseifolius can reduce uric acid in mice with hyperuricemia nephropathy and has a certain protective effect on the kidneys.The mechanism may be related to the inhibition of uric acid reabsorption,and the specific mechanistic details should be further investigated.

Objective To explore the role of TMAO from gut microbiota in non-alcoholic fatty liver disease(NAFLD),we detected the serum level of TMAO and its precursor metabolites in NAFLD,as well as the expression level of Eubacterium rectum,Bacteroidetes multiforme,Lactobacillus and bifidobacterium in the intestinal flora.Methods We collected 118 subjects and divided into NAFLD group(86 cases)and healthy control group(32 cases)randomly.We also detected the serum level of TMAO and its precursor metabolites in subjects by high performance liquid chromatography tandem mass spectrometry detection(LC-MS),and the expression of target bacterial DNA was detected by qRT-PCR.Results Serum TMAO,TMA and choline levels were significantly increased in NAFLD(P<0.05),and liver fat content was positively correlated with TMAO(P<0.05).The expression level of Lactobacillus and Eubacterium rectum in NAFLD group were increased(P<0.05);the expression level of Bifidobacterium and Bacteroides multiform were decreased(P<0.05).The serum TMAO level was positively correlated with Eubacterium rectum(r=0.280,P<0.05),and negatively correlated with Bifidobacterium(r=-0.332,P<0.05).Conclusion The level of TMAO in serum shows a positive correlation with NAFLD.The structure of intestinal flora in individuals with NAFLD is altered and linked to TMAO.This suggests that the intestinal flora may have a significant impact on the development of NAFLD through TMAO.

Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H₂O₂), which is then used in the Cu⁺-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

Objective To explore the metabolic markers of social anxiety disorder in schizophrenia patients with social anxiety disorder through metabolomic sequencing analysis.Methods From December 2022 to December 2023,a case-control study was carried out in the Neuropsychiatric Prevention and Control Hospital of Fuzhou Second General Hospital.One hundred sixty patients with schizophrenia were included in the study.The Diagnostic and Statistical Manual of Mental Disorders,fourth edition(DSM-Ⅳ)and Liebowitz social anxiety scale(LSAS)scores were used to classify subjects as patients with social anxiety disorder(n=64)and controls without social anxiety disorder(n=96).Peripheral blood samples were collected for non-targeted metabolomic sequencing,and the metabolites with statistical differences were analyzed by receiver operating characteristic(ROC)curve to find metabolic markers that may affect social anxiety disorder in schizophrenia patients.Results There were significant differences in 12 metabolites between the two groups(P<0.05).In ROC curve analysis,the top 3 metabolites with area under curve(AUC)values were 3-O-trans-coumaryl-alphetolic acid(AUC=0.637),3-mercaptopropionic acid(AUC=0.602)and nona-2-acylcarnitine(AUC=0.600).Conclusion In this study,the potential diagnostic metabolic markers of 3-O-trans-coumaryl-alphitoic acid,3-mercaptopropionic acid,nonyl-2-acylcarnitine as diagnostic metabolic markers can effectively distinguish patients with schizophrenia social anxiety disorder from patients with schizophrenia without social anxiety disorder.

Ischemic stroke（IS） is a common cerebrovascular disease in clinics，with a high disability rate. In recent years，the incidence of IS has gradually increased，especially in young people，which seriously affects the physical and mental health and quality of life of patients. Western medicine has made some progress in the treatment of IS but still faces some limitations. Therefore， choosing a measure that can assist in the treatment of IS is particularly important. A large number of studies have confirmed that traditional Chinese medicine can treat IS based on the effective ingredients and extracts of traditional Chinese medicine monomers and formulas，utilizing advantages such as multiple targets，multiple bioactive ingredients，multiple systems，and fewer adverse reactions to ensure the safety and effectiveness of the treatment pathway. At present，the mechanism of action of traditional Chinese medicine in treating IS can be achieved by intervening in various signaling pathways，mainly including secretory glycoprotein/β-catenin（Wnt/β-catenin） signaling pathway，phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway，nuclear factor kappa-B（NF-κB） signaling pathway，Toll-like receptor 4/NOD-like receptor protein 3（TLR4/NLRP3） signaling pathway，mitogen-activated protein kinase（MAPK） signaling pathway，and neurogenic site-gap homologous protein（Notch） signaling pathway. This article summarized the relationship between IS and related signaling pathways in recent years，as well as the regulation of IS-related pathways and corresponding mechanisms by traditional Chinese medicine，so as to provide a reference for future clinical and experimental research on IS.