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.

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 downregulated metabolites in sera of RLPS 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 [¹³C₅]-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.

Objective To explore the factors influencing cognitive frailty in elderly inpatients with chronic heart failure(CHF)during hospitalisation,8 prediction models were developed with various machine learning algorithms to identify the best model as a guidance for medical staff on clinical interventions.Methods Convenience sampling method was used to select 650 elderly CHF inpatients who stayed in our hospital between September 2023 and June 2024 as the study objects in the cross-sectional investigation.A total of 607 patients had completed the study.The patients were divided into a cognitive frailty group and a non-cognitive frailty group according to the presence or absence of cognitive frailty.Variables were initially screened using univariate analysis and stepwise Logistic regression.The total sample was then randomly divided into a training set(n=424)and a testing set(n=183)of a 7:3 ratio.Eight predictive models were created using the algorithms of neural network(NN),k-nearest neighbour(KNN),linear discriminant analysis(LDA),support vector machine(SVM),naive Bayes(NB),logistic regression,decision tree(DT)and random forest(RF)on the training set.The predictive performance of the models was compared using the data of the testing set.Results The prevalence of cognitive frailty in elderly CHF inpatients was 48.3%.Results of Logistic regression showed that age,marital status,education,body mass index,multi-morbidity,nutritional status,medication,frequency of weekly exercise and the living conditions were the key factors(P<0.05).The overall accuracy in classification of the eight predictive models ranged from 0.803 to 0.847,with F1-values of 0.778 to 0.833,precision of 0.848 to 0.897,and recall rate of 0.700 to 0.778.The area under the receiver operating characteristic curve was 0.820 to 0.901.Conclusion Of the eight predictive models,the prediction model created with LDA shows the best performance and prediction in terms of comprehensive prediction metrics,while the prediction model created with NN shows the worst performance in comprehensive prediction.

Objective To explore the factors influencing cognitive frailty in elderly inpatients with chronic heart failure(CHF)during hospitalisation,8 prediction models were developed with various machine learning algorithms to identify the best model as a guidance for medical staff on clinical interventions.Methods Convenience sampling method was used to select 650 elderly CHF inpatients who stayed in our hospital between September 2023 and June 2024 as the study objects in the cross-sectional investigation.A total of 607 patients had completed the study.The patients were divided into a cognitive frailty group and a non-cognitive frailty group according to the presence or absence of cognitive frailty.Variables were initially screened using univariate analysis and stepwise Logistic regression.The total sample was then randomly divided into a training set(n=424)and a testing set(n=183)of a 7:3 ratio.Eight predictive models were created using the algorithms of neural network(NN),k-nearest neighbour(KNN),linear discriminant analysis(LDA),support vector machine(SVM),naive Bayes(NB),logistic regression,decision tree(DT)and random forest(RF)on the training set.The predictive performance of the models was compared using the data of the testing set.Results The prevalence of cognitive frailty in elderly CHF inpatients was 48.3%.Results of Logistic regression showed that age,marital status,education,body mass index,multi-morbidity,nutritional status,medication,frequency of weekly exercise and the living conditions were the key factors(P<0.05).The overall accuracy in classification of the eight predictive models ranged from 0.803 to 0.847,with F1-values of 0.778 to 0.833,precision of 0.848 to 0.897,and recall rate of 0.700 to 0.778.The area under the receiver operating characteristic curve was 0.820 to 0.901.Conclusion Of the eight predictive models,the prediction model created with LDA shows the best performance and prediction in terms of comprehensive prediction metrics,while the prediction model created with NN shows the worst performance in comprehensive prediction.

Objective To investigate the relationship between two-lung ventilation (TLV) with single-lumen endotracheal tube (SLT), one-lung ventilation (OLV) with double-lumen endotracheal tube (DLT) and postoperative pulmonary complications (PPCs) after total thoracoscopic cardiac surgery. Methods The clinical data of patients who underwent totally thoracoscopic cardiac surgeries in the Guangdong Provincial People’s Hospital from October 2019 to October 2021 were retrospectively analyzed. The patients were divided into 2 group according to the type of endotracheal tube, including a SLT group and a DLT group. Baseline data, surgical variables and PPCs were compared. The influencing factors of PPCs in the two groups were analyzed by binary logistic regression analysis. Results Finally 349 patients were enrolled, including 180 males and 169 females with an average age of (50.0±14.8) years. There were 219 patients in the SLT group and 130 patients in the DLT group. There was no statistical difference in baseline data, surgical variables or PPCs between the two groups (P＞0.05). Binary logistic regression analysis showed that PPCs were related to body mass index in the SLT group (OR=0.778, 95%CI 0.637 to 0.951, P=0.014) and preoperative smoking history in the DLT group (OR=0.058, 95%CI 0.004 to 0.903, P=0.042). Conclusion For the patients who undergo totally thoracoscopic cardiac surgery, TLV with SLT and OLV with DLT show no significant association with PPCs. At the same time, PPCs are associated with body mass index in the SLT group, while associated with preoperative smoking history in the DLT group.

Objective To explore basement membrane markers and potential drugs for treatment in idiopathic pulmona-ry fibrosis(IPF).Methods IPF-related datasets were downloaded from the Gene Expression Omnibus(GEO)database,processed to construct basement membrane gene expression matrices associated with IPF,and screened for differential basement membrane genes(DEBMs);DEBMs were enriched for function and pathways,and machine learning algorithms were used to ob-tain candidate signature genes,receiver operating characteristic(ROC)curves were used to identify signature genes and con-struct a nomogram.We performed ssGSEA analysis to explore the correlation between signature genes and immune cells and their functions and predicted the corresponding miRNAs and therapeutic drugs by signature genes.Results A total of 56 DEBMs were extracted;enrichment analysis showed that DEBMs were mainly enriched in"extracellular matrix tissue","extracellular structural tissue",etc.,and were closely related to"ECM-receptor interaction"and"local adhesion spot"pathways.The ma-chine learning has identified six candidate signature genes(TIMP3,P3H2,ITGA7,ITGA4,ADAMTS2,COL8A2),all of which meet the requirements of the signature genes by the ROC curve test,and the nomogram diagnostic value was outstanding(AUC=0.991 523);B cells and Macrophages in IPF were significantly different from the normal group.Finally,miRNAs were predicted to be dominated by miR-4305,miR-3684,progesterone,and tert-butyl hydroperoxide as therapeutic agents with strong relevance to IPF.Conclusion Signature genes and predictive miRNAs may serve as novel markers for IPF diagnosis,and pre-dictive drugs may be a potential source of drugs for treating IPF.

The increasing incidence of arteriosclerosis has become a significant global health burden. Arteriosclerosis is characterized by the thickening and hardening of arterial walls, which can lead to the narrowing or complete blockage of blood vessels. However, the pathogenesis of the disease remains incompletely understood. Recent research has shown that stem and progenitor cells found in the bone marrow and local vessel walls play a role in the development of arteriosclerosis by differentiating into various types of vascular cells, including endothelial cells, smooth muscle cells, fibroblasts, and inflammatory cells. This review aims to provide a comprehensive understanding of the role of stem and progenitor cells in the pathogenesis of arteriosclerosis, shedding light on the underlying mechanisms and potential therapeutic approaches for this disease.

The increasing incidence of arteriosclerosis has become a significant global health burden. Arteriosclerosis is characterized by the thickening and hardening of arterial walls, which can lead to the narrowing or complete blockage of blood vessels. However, the pathogenesis of the disease remains incompletely understood. Recent research has shown that stem and progenitor cells found in the bone marrow and local vessel walls play a role in the development of arteriosclerosis by differentiating into various types of vascular cells, including endothelial cells, smooth muscle cells, fibroblasts, and inflammatory cells. This review aims to provide a comprehensive understanding of the role of stem and progenitor cells in the pathogenesis of arteriosclerosis, shedding light on the underlying mechanisms and potential therapeutic approaches for this disease.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

OBJECTIVES: In this study, we explored how adiponectin mediated urotensin II (UII)‍-induced tumor necrosis factor-‍α (TNF-‍α) and α‍-smooth muscle actin (α‍-SMA) expression and ensuing intracellular signaling pathways in adventitial fibroblasts (AFs). METHODS: Growth-arrested AFs and rat tunica adventitia of vessels were incubated with UII and inhibitors of signal transduction pathways for 1‍‒‍24 h. The cells were then harvested for TNF-α receptor (TNF-‍α-R) messenger RNA (mRNA) and TNF-‍α protein expression determination by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Adiponectin and adiponectin receptor (adipoR) expression was measured by RT-PCR, quantitative real-time PCR (qPCR), immunohistochemical analysis, and cell counting kit-8 (CCK-8) cell proliferation experiments. We then quantified TNF-α and α-SMA mRNA and protein expression levels by qPCR and immunofluorescence (IF) staining. RNA interference (RNAi) was used to explore the function of the adipoR genes. To investigate the signaling pathway, we applied western blotting (WB) to examine phosphorylation of adenosine 5'-monophosphate (AMP)‍-activated protein kinase (AMPK). In vivo, an adiponectin (APN)‍-knockout (APN-KO) mouse model mimicking adventitial inflammation was generated to measure TNF-α and α‍-SMA expression by application of qPCR and IF, with the goal of gaining a comprehensive atlas of adiponectin in vascular remodeling. RESULTS: In both cells and tissues, UII promoted TNF-α protein and TNF-α-R secretion in a dose- and time-dependent manner via Rho/protein kinase C (PKC) pathway. We detected marked expression of adipoR1, T-cadherin, and calreticulin as well as a moderate presence of adipoR2 in AFs, while no adiponectin was observed. Globular adiponectin (gAd) fostered the growth of AFs, and acted in concert with UII to induce α-SMA and TNF-α through the adipoR1/T-cadherin/calreticulin/AMPK pathway. In AFs, gAd and UII synergistically induced AMPK phosphorylation. In the adventitial inflammation model, APN deficiency up-regulated the expression of α-SMA, UII receptor (UT), and UII while inhibiting TNF-‍α expression. CONCLUSIONS From the results of our study, we can speculate that UII induces TNF‍-‍α protein and TNF-‍α‍-R secretion in AFs and rat tunica adventitia of vessels via the Rho and PKC signal transduction pathways. Thus, it is plausible that adiponectin is a major player in adventitial progression and could serve as a novel therapeutic target for cardiovascular disease administration.
Mice ; Rats ; Animals ; Adventitia/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Calreticulin/metabolism* ; Vascular Remodeling ; AMP-Activated Protein Kinases/metabolism* ; Cells, Cultured ; RNA, Messenger/genetics* ; Inflammation