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.

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.

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.

Objective:To investigate HER2 mRNA expression in breast cancer with HER2 immunohistochemistry (IHC) 0 and to analyze the feasibility of distinguishing between the tumor with HER2 μltra-low expression and the one without expression of HER2 (no staining by IHC) by HER2 mRNA level preliminarily.Methods:HER2 mRNA was analyzed by reverse transcription digital PCR in 41 cases of formalin-fixed paraffin-embedded surgical tissue samples of invasive breast cancer obtained between January 2020 and March 2023 at Peking Union Medical College Hospital. The cohort included 21 HER2 IHC 1+ and 20 IHC 0 (12 ultra-low and 8 non-expression of HER2). HER2 mRNA expression level was quantitatively evaluated by the FAM (HER2)/VIC (reference gene) ratio.Results:The expression of HER2 mRNA for the cases with 1+, ultra-low, and non-expression of HER2 by IHC was 0.30 to 1.78 (average 0.90, median 0.82), 0.55 to 1.51 (average 0.93, median 0.90) and 0.22 to 0.78 (average 0.41, median 0.36), respectively. For the mean and median HER2 mRNA levels, there was no significant difference between HER2 IHC 1+ and HER2 ultra-low expression diseases ( P=0.757). A remarkable difference in HER2 gene expression was found between the tumors with 1+ and non-expression of HER2 by IHC ( P=0.002). And, HER2 ultra-low cases contained statistically higher levels of HER2 mRNA compared with non-expression of HER2 subgroup by IHC ( P=0.001). Conclusions:Based on HER2 mRNA, HER2 non-expression and HER2 weak expression (including HER2 IHC 1+ and ultra-low) belong to two different types of the tumor and the disease with HER2 IHC 1+ and HER2 ultra-low expression may be the same. It is necessary to further test the performance of HER2 mRNA detection for stratifying the HER2 weak expression subgroup and to determine the threshold.

Objective:To investigate the clinical and pathological characteristics of breast cancer with HER2 low expression.Methods:The data from 3 422 patients with invasive breast cancer which archived in Peking Union Medical College Hospital between April 2019 and July 2022 were retrospectively reviewed. Among them, 136 patients were treated with neoadjuvant chemotherapy. The tumor size, histological type, tumor differentiation, lymph node metastasis, Ki-67 index, the status of estrogen receptor, progesterone receptor and HER2 as well as pathological complete response (pCR) rate were collected.Results:The HER2 status of 3 286 patients without neoadjuvant therapy, 616 (616/3 286, 18.7%) score 0, 1 047 (1 047/3 286, 31.9%) score 1+, 1 099 (1 099/3 286,33.4%) score 2+ and 524 (524/3 286,15.9%) score 3+ by immunohistochemistry (IHC). Among the 1 070 IHC 2+ cases, 161 were classified as HER2 positive by reflex fluorescence in situ hybridization (FISH) assay. In our cohort, 1 956 cases of HER2-low (IHC 1+ and IHC 2+/FISH-) breast cancer were identified. Compared to the HER2 IHC 0 group, HER2-low tumors more frequently occurred in patients with hormone receptor (HR) positive ( P<0.001), Ki-67 index below 35% ( P<0.001), well or moderate differentiation ( P<0.001) and over the age of 50 ( P=0.008). However, there were no significant differences in histological type, tumor size, and lymph node metastasis between HER2-low and HER2 IHC 0 group. For patients who had neoadjuvant therapy, the pCR rate in the patients with HER2-low was lower than those with HER2 IHC 0 (13.3%, 23.9%), but there was no significant difference. Although HER2-low breast cancers showed a slightly lower pCR rate than HER2 IHC 0 tumors, no remarkable difference was observed between tumors with HER2-low and HER2 IHC 0 regardless of hormone receptor status. Conclusions:The clinicopathological features of HER2-low breast cancers are different from those with HER2 IHC 0. It is necessary to accurately distinguish HER2-low breast cancer from HER2 IHC 0 and to reveal whether HER2-low tumor is a distinct biological entity.

Objective:To investigate the association between gestational blood pressure and neurodevelopment in 2-year-old children.Methods:Based on the"Wuhan Healthy Baby Birth Cohort", 3 754 mother-infant pairs were enrolled in this study. Based on multiple blood pressure measurements during pregnancy, the mean, cumulative, and variability of blood pressure throughout the entire pregnancy and each trimester were calculated. Blood pressure variability was evaluated using standard deviation (SD), coefficient of variability (CV), and variability independent of mean (VIM). Follow-up testing of neurodevelopment in infants and young children at the age of two was conducted to obtain the Mental Development Index (MDI) and the Psychomotor Development Index (PDI). The multivariate linear regression and generalized estimation equation were used to analyze the association between gestational blood pressure data and neurodevelopmental index.Results:The age of 3 754 pregnant women was (29.1±3.6) years, with a pre-pregnancy BMI of (20.9±2.7) kg/m2 and a gestational age of (39.3±1.2) weeks. The birth weight of 3 754 children was (3 330.9±397.7) grams, and the birth length was (50.3±1.6) centimeters. The results of the multivariate linear regression analysis showed that after adjusting for relevant confounding factors, the mean blood pressure, cumulative blood pressure, standard deviation of blood pressure, coefficient of variation of blood pressure, independent blood pressure variability of systolic blood pressure, diastolic blood pressure, and pulse pressure throughout pregnancy were negatively associated with the MDI and PDI scores of 2-year-old children. The analysis results of the generalized estimation equation showed that after adjusting for relevant confounding factors, the average systolic blood pressure in the first, second, and third trimesters was negatively associated with MDI/PDI. The negative association between cumulative blood pressure and MDI/PDI was only found in the first trimester. The negative association between blood pressure variation during pregnancy and MDI/PDI was mainly concentrated in the second and third trimesters.Conclusion:There is a negative association between gestational blood pressure and the neurodevelopmental index of 2-year-old children.