Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Drug repurposing offers a promising alternative to traditional drug development and significantly re-duces costs and timelines by identifying new therapeutic uses for existing drugs.However,the current approaches often rely on limited data sources and simplistic hypotheses,which restrict their ability to capture the multi-faceted nature of biological systems.This study introduces adaptive multi-view learning(AMVL),a novel methodology that integrates chemical-induced transcriptional profiles(CTPs),knowledge graph(KG)embeddings,and large language model(LLM)representations,to enhance drug repurposing predictions.AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning(MVL),matrix factorization,and ensemble optimization techniques to integrate heterogeneous multi-source data.Comprehensive evaluations on benchmark datasets(Fdata-set,Cdataset,and Ydataset)and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art(SOTA)methods,achieving superior accuracy in predicting drug-disease associations across multiple metrics.Literature-based validation further confirmed the model's predictive capabilities,with seven out of the top ten predictions corroborated by post-2011 evidence.To promote transparency and reproducibility,all data and codes used in this study were open-sourced,providing resources for pro-cessing CTPs,KG,and LLM-based similarity calculations,along with the complete AMVL algorithm and benchmarking procedures.By unifying diverse data modalities,AMVL offers a robust and scalable so-lution for accelerating drug discovery,fostering advancements in translational medicine and integrating multi-omics data.We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.

Objective To investigate the current status of pain crisis in patients with advanced colorectal cancer(CRC)and analyze its influencing factors.Methods A total of 186 patients with advanced CRC who were hospitalized in the Oncology Department,the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from June 2024 to March 2025 were selected as the subjects of the investigation.General information questionnaires numerical rating scale,distress tolerance scale,self-rating anxiety scale,self-rating depression scale and quality of life assessment scales were used for the investigation.Logistic regression was used to analyze the influencing factors of pain crisis in patients with advanced CRC.Results Among the 186 CRC patients,87 experienced pain crises,with an incidence rate of 46.8％.The results indicated that pain type,use of analgesics,traditional Chinese medicine adjuvant therapy,metastasis radiotherapy and chemotherapy,pain intensity and pain tolerance were important influencing factors for pain crises in advanced CRC patients.Conclusion The incidence of pain crisis in patients with advanced CRC is relatively high.Nursing staff should promptly identify patients with pain crisis and implement targeted intervention strategies for high-risk patients to reduce the risk of pain crisis.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective:To investigate the correlation between relative fat mass(RFM)and Estimated Glomerular Filtration Rate(eGFR)in an elderly hypertensive population.Methods:This cross-sectional study enrolled elderly hypertensive individuals aged 65 years and older from Huai'an city between June 2023 and December 2023.Clinical data for these subjects were collected, and RFM and eGFR were calculated according to established formulas.Subsequently, the subjects were divided into two groups based on their eGFR levels: the eGFR normal group and the eGFR decreased group.Differences between these two groups were compared.Multivariate logistic regression models were employed to analyze the association between RFM and eGFR, and a subgroup analysis was conducted.The predictive value of RFM for renal function decline was evaluated using receiver operating characteristic curves(ROC).Results:Among the 2, 603 subjects, 921(35.4%)were assigned to the eGFR decreased group, while 1, 682(64.6%)were assigned to the eGFR normal group.The proportion of males, married individuals, smokers, and alcohol drinkers, as well as diastolic blood pressureand cultural levels, were significantly lower in the eGFR decreased group compared to the eGFR normal group (all P<0.05). Conversely, the duration of hypertension, proportion of comorbidities, age, fasting blood glucose, triglycerides, low-density lipoprotein cholesterol(LDL-C), relative fat mass(RFM), visceral fat index(VAI), dysfunctional obesity index(DAI), body roundness index(BRI), and conicity index(C-index)were all significantly higher in the eGFR decreased group compared to the eGFR normal group(all P<0.05). After adjusting for confounding factors, multivariate logistic regression analysis revealed that when RFM was treated as a continuous variable, the risk of eGFR decline increased with rising RFM(odds ratio[ OR]=1.035, 95% confidence interval[95% CI]: 1.008-1.063, P=0.010). When grouped according to RFM quartile levels(in ascending order)into Q1(<26.22), Q2(26.22-<30.53), Q3(30.53-<39.26), and Q4(≥39.26), using the Q1 group as a reference, the risk of eGFR decline increased in the Q3( OR=1.691, 95% CI: 1.777-2.430, P=0.004)and Q4( OR=1.743, 95% CI: 1.118-2.717, P=0.014)groups.In the subgroup analysis, gender( P-interaction=0.034)and smoking( P-interaction=0.012)were identified as having significant interaction effects on RFM and the decline in eGFR.In the male subgroup( OR=1.067, 95% CI: 1.027-1.108, Ptrend=0.001)and the smoking subgroup( OR=1.109, 95% CI: 1.026-1.199, Ptrend=0.009), the risk of eGFR decline significantly increased with higher levels of RFM.The restricted cubic spline(RCS)analysis indicated that when RFM exceeded 30.609, the risk of eGFR decline increased with rising RFM levels, demonstrating a non-linear correlation between RFM and the risk of eGFR decline( Pnonlinearity=0.048 5). The ROC curve analysis revealed that the area under the curve(AUC)for RFM in predicting eGFR reduction was 0.635(95% CI: 0.613-0.657, P1<0.001), which was significantly higher than the AUC for VAI(AUC=0.573, 95% CI: 0.550-0.596, P2<0.001), DAI(AUC=0.562, 95% CI: 0.539-0.584, P2<0.001), BRI(AUC=0.564, 95% CI: 0.541-0.587, P2<0.001), and the C-index(AUC=0.536, 95% CI: 0.513-0.559, P2<0.001). Conclusions:Elevated RFM is an independent risk factor for eGFR decline in elderly hypertensive individuals.There exists a significant interaction between gender and smoking with respect to the risk of RFM and eGFR decline.Additionally, RFM demonstrates a notable predictive value for eGFR decline in elderly hypertensive individuals.

Objective To explore the role and mechanism of RNA m6A methyltransferase Wilms'tumor 1-associated protein(WTAP)in epithelial-mesenchymal transition(EMT)of glioblastoma cells and its association with transcription factor JUNB.Methods(1)Based on the Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases,the expression levels of transforming growth factor β(TGF-β),WTAP,and JUNB in glioblastoma multiforme(GBM)and normal brain tissues were analyzed,as well as their diagnostic and prognostic values for GBM.The correlation of TGF-β,WTAP,and JUNB with gliomas of different WHO grades was analyzed using the Chinese Glioma Genome Atlas(CGGA)database.Spearman correlation analysis was performed to assess the correlation between TGF-β and m6A methyltransferases.(2)An EMT model was established in human astrocytoma U87-MG cells through TGF-β1 induction.qRT-PCR and Western blotting were employed to detect the expression levels of WTAP,JUNB,matrix metalloproteinase 2(MMP2),and N-cadherin.The migration capacity of U87-MG cells was evaluated by wound-healing and Transwell assays.An m6A RNA methylation quantification kit(colorimetric)was used to detect RNA m6A methylation modification levels.A stable cell line with low expression of WTAP was constructed to investigate the effects of WTAP knockdown on the migration ability of U87-MG cells,as well as the expression of JUNB.(3)A protein-protein interaction network was constructed using STRING database and GeneMANIA database,followed by gene ontology(GO)and KEGG pathway enrichment analyses to explore the biological processes,molecular functions,cellular components,and signaling pathways potentially involved in TGF-β/WTAP/JUNB.Gene set enrichment analysis(GSEA)was performed on JUNB-related genes to investigate their potential downstream signaling pathways.Results(1)The expression levels of TGF-β,WTAP,and JUNB were significantly higher in GBM(P<0.001),positively correlated with WHO grades of glioma(P<0.001).Glioma patients with high expression of all three genes had shorter overall and disease-free survival(P<0.001).Spearman analysis showed that the expression of TGF-β in GBM was positively correlated with WTAP(r=0.175,P=0.023),but no significant correlation with other m6A methyltransferases(P>0.05).(2)After TGF-β1 treatment,the level of m6A methylation modification of total RNA in U87-MG cells significantly increased(P<0.001).Wound-healing assay and Transwell assay results showed that the migration ability of U87-MG cells was significantly increased after TGF-β1 treatment(P<0.01),while WTAP knockdown significantly reduced the migration ability of U87-MG cells(P<0.01).qRT-PCR and Western blotting results showed that the mRNA and protein expression levels of WTAP,N-Cadherin,MMP2,and JUNB in U87-MG cells were significantly increased after 48 h of TGF-β1 induction(P<0.001),while WTAP knockdown significantly reduced the mRNA and protein expression of JUNB(P<0.001).(3)The TGF-β/WTAP/JUNB-related protein-protein interaction network was constructed,which was primary involved in mRNA modification and EMT.GSEA results showed that JUNB-related signaling pathways were closely associated with glioma malignant progression.Conclusions TGF-β,WTAP,and JUNB are all associated with GBM malignant progression and poor patient prognosis.TGF-β may enhance total RNA m6A modification by promoting the expression of m6A methyltransferase WTAP,and WTAP subsquentaly upregulates transcription factor JUNB,thereby promoting EMT and malignant progression of GBM.

Objective:To investigate the effects of Japan tallow(JT)on liver injury and gut microbiota regulation in type 2 diabetes mellitus(T2DM)mice,thereby providing a theoretical basis for developing therapeutic edible oils for diabetes treatment.Methods:T2DM animal model was established through a combined approach of nutritional intervention and chemical induction.Experimental animals were first fed a high-fat diet(HFD)for 6 weeks,followed by intraperitoneal injection of freshly prepared streptozotocin(STZ).After successful model establishment,the mice were divided into five groups(n=6 per group):control group without any intervention;T2DM group;HFD reversion to standard chow group;metformin group;and JT intervention group,which received respective treatments for 4 weeks.At the endpoint,fresh fecal samples were collected from all groups,and the gut microbiota composition was analyzed using 16s rDNA high-throughput sequencing.Liver histopathological changes were examined using histological methods.Results:Compared with the normal control(ND),T2DM mice showed significantly increased fasting blood glucose(FBG)levels,with evident hepatocyte lipid accumulation,steatosis,inflammatory cell infiltration,and widespread vacuolar and fatty degeneration.After Japan tallow(JT)intervention,FBG levels decreased significantly,liver color approximated normal appearance,and pathological morphology improved noticeably.16s rDNA sequencing analysis demonstrated that JT treatment could effectively regulate the intestinal microbiota structure in T2DM mice.Increased microbial α-diversity indices(Chao1,observed_species,Faith_pd,Simpson);At the phylum level,increased Verrucomicrobia abundance while decreased Proteobacteria were detected;At the family level,elevated Bifidobacteriaceae and reduced Porphyromonadaceae were seen;At the genus level,Bifidobacterium was promoted and Akkermansia proliferat while Escherichia and Klebsiella were downregulated.Conclusions:Japan tallow exhibits significant effects in alleviating liver tissue damage and regulating intestinal microbiota disorders in T2DM mice,our study indicated new theoretical basis for the research and development of potential strategy for diabetes.

Objectives:To investigate the distribution and change of the burden of cardiovascular diseases attributable to tobacco consumption in China and the world from 1990 to 2021.Methods:Based on Global Burden of Disease(GBD)2021 database,age standardized mortality and age standardized disability-adjusted life year(DALY)rates and estimated annual percentage change(EAPC)from cardiovascular disease(including ischemic heart disease,stroke,atrial fibrillation and flutter,aortic aneurysm,peripheral artery disease)attributable to tobacco consumption were analyzed.The association of the human development index(HDI)and social demographic index(SDI)with age-standardized mortality was also analyzed.Results:Compared to 1990,the global burden of cardiovascular diseases attributable to smoking declined in 2021,age-standardized mortality decreased from 57.2/100 000 to 26.3/100 000(EAPC=-1.81%,95% CI:-2.00% to-1.63% ).The global burden of cardiovascular diseases attributable to second-hand smoke also decreased,age-standardized mortality decreased from 11.4/100 000 to 8.3/100 000(EAPC=-1.72%,95% CI:-1.91% to-1.53% ).In China,the burden of cardiovascular diseases attributable to smoking also decreased,age-standardized mortality decreased from 52.2/100 000 to 39.6/100 000(EAPC=-1.23%,95% CI:-1.44%-1.02% );the burden of cardiovascular diseases attributable to second-hand smoke decreased,age-standardized mortality decreased from 15.3/100 000 to 14.7/100 000(EAPC=-1.26%,95% CI:-1.63% to-0.90% ).Notably,the decrease in cardiovascular diseases burden attributable to second-hand smoke among Chinese women was more significant than the global level,the age-standardized mortality rate of Chinese women decreased from 17.9/100 000 to 14.5/100 000(EAPC=-2.24%,95% CI=-2.78%～-1.86% ).Among the five types of cardiovascular diseases attributable to tobacco consumption globally and in China,the age-standardized mortality and age-standardized DALY rates of aortic aneurysm,ischemic heart disease and peripheral artery disease were higher.Globally,ischaemic heart disease is the leading cause of death,accounting for 60.2% in 1990 and 61.7% in 2021,while stroke is the leading cause of death in China,accounting for 68.1% and 51.4% in 1990 and 2021,respectively.In addition,HDI and SDI are the two main factors affecting the disease burden.In regions and countries with SDI>7.2,age standardized mortality is below our forecast line.In the later part of the forecast,China's age standardized mortality showed a downward trend,possibly due to changes in tobacco control measures.Conclusions:Over the past 30 years,the burden of cardiovascular diseases attributed to tobacco consumption has decreased globally and in China.The decline in disease burden has been most pronounced among women.However,in countries and regions with an SDI below 7.2,the burden of disease remains significant high.Therefore,it is necessary to take tobacco control measures in key regions(China,East Asia,Central Europe,Central Asia and Southeast Asia)to actively reduce smoking rates and exposure to secondhand smoke in public places,so as to reduce the burden of cardiovascular diseases.

Objective To explore the effect and mechanism of knockdown of mitochondrial transcription factor A(TFAM)on the growth of gastrointestinal stromal tumor(GIST)cells mediated by tumor-associated macrophages(TAMs)polarization.Methods Human acute leukemia mononuclear macrophage cell line THP-1 induced by phobate and interleukin(IL)-4 was used to establish TAMs,lentivirus shRNA TFAM and negative control shRNA NC were transfected into TAMs,which were recorded as TAMs+sh-TFAM group and TAMs+sh-NC group,respectively,the untransfected cells were recorded as the TAMs group.The mRNA expression of TFAM,IL-10 and arginase-1(Arg-1)was detected by qRT-PCR.The TFAM protein expression was detected by Western blot.The expression level of CD206 was detected by flow cytometry.The human GIST cell line GIST-T1 were divided into GIST-T1 group,TAMs+GIST-T1 group,TAMs+sh-NC+GIST-T1 group,TAMs+sh-TFAM+GIST-T1 group,and treated with fresh medium containing different TAMs culture supernatants.The cell proliferation and apoptosis levels were detected by CCK-8,EdU staining and Annexin V-FITC/PI double staining respectively.Results Compared with TAMs group and TAMs+sh-NC group,the TFAM mRNA and protein expression levels of THP-1 cells in TAMs+sh-TFAM group were significantly down-regulated(P<0.05).Compared with control group,the expression levels of CD206 and IL-10 and Arg-1 mRNA of THP-1 cells in TAMs group were significantly increased(P<0.05).Compared with TAMs+sh-NC group,the expression levels of CD206 and IL-10 and Arg-1 mRNA of THP-1 cells in TAMs+sh-TFAM group were significantly decreased(P<0.05).Compared with GIST-T1 group,the proliferative activity of GIST-T1 cells and EdU positive cells rate in TAMs+GIST-T1 group were significantly increased(P<0.05),while the apoptosis rate was significantly decreased(P<0.05).Compared with TAMs+sh-NC+GIST-T1 group,the proliferative activity of GIST-T1 cells and EdU positive cells rate in TAMs+sh-TFAM+GIST-T1 group were significantly decreased(P<0.05),while the apoptosis rate was significantly increased(P<0.05).Conclusion Knockdown of TFAM can inhibit the polarization of TAMs to M2 phenotype,thus inhibiting the proliferation of GIST cells,promoting cell apoptosis,and preventing the progression of GIST.

Objective:To retrieve, evaluate, and summarize the best evidence on ultrasound-guided placement and tip confirmation of peripherally inserted central catheter (PICC) in neonates.Methods:Based on the "6S" evidence pyramid model, literature on ultrasound-guided placement and tip confirmation of PICC in neonates was sequentially searched on guideline websites, professional society websites, and journal databases. The search period was from database establishment to September 30, 2024. Two researchers used uniform criteria for independent quality assessment and evidence extraction from the literature, and the extracted evidence was integrated and summarized.Results:A total of ten articles were included, including five guidelines, one clinical decision, two expert consensus, one Meta-analysis, and one evidence summary. Thirty pieces of evidence were developed in six aspects: personnel qualification and training, catheter selection, assessment of placement veins, ultrasound-guided PICC puncture in neonates, PICC tip confirmation in neonates, and prevention and management of malposition.Conclusions:This study summarizes the best evidence for ultrasound-guided placement and tip confirmation of PICC in neonates. It is recommended that evidence be selected and applied to develop a standardized process for neonatal PICC placement in conjunction with the resource environment of the department and the skill level of the healthcare professionals to improve the quality of nursing and to ensure the safe and effective use of the PICC in clinical practice.