Objective To introduce a modified technique of right ventricular outflow tract (RVOT) reconstruction using a handmade bicuspid pulmonary valve crafted from expanded polytetrafluoroethylene (ePTFE) and to summarize the early single-center experience. Methods Patients with complex congenital heart diseases (CHD) who underwent RVOT reconstruction with a handmade ePTFE bicuspid pulmonary valve due to pulmonary regurgitation at Guangdong Provincial People’s Hospital from April 2021 to February 2022 were selected. Postoperative artificial valve function and right heart function indicators were evaluated. Results A total of 17 patients were included, comprising 10 males and 7 females, with a mean age of (18.18±12.14) years and a mean body weight of (40.94±19.45) kg. Sixteen patients underwent reconstruction with a handmade valved conduit, with conduit sizes ranging from 18 to 24 mm. No patients required mechanical circulatory support, and no in-hospital deaths occurred. During a mean follow-up period of 12.89 months, only one patient developed valve dysfunction, and no related complications or adverse events were observed. The degree of pulmonary regurgitation was significantly improved post-RVOT reconstruction and during follow-up compared to preoperative levels (P<0.001). Postoperative right atrial diameter, right ventricular diameter, and tricuspid regurgitation area were all significantly reduced compared to preoperative values (P<0.05). Conclusion The use of a 0.1 mm ePTFE handmade bicuspid pulmonary valve for RVOT reconstruction in complex CHD is a feasible, effective, and safe technique.

Objective To find out whether photobiomodulation(PBM)can mitigate cognitive dysfunction caused by chronic stress by affecting levels of adenosine triphosphate(ATP)and adenosine receptors.Methods Twenty-four C57BL/6J mice were randomly divided into a control group,a stress group,and a treatment group.Chronic unpredictable mild stress was used to establish a mouse model of stress.Six weeks into modeling,the treatment group was subjected to one week of PBM interventions.Behavioral tests were conducted to observe behavioral changes in the mice.Western blotting(WB)was used to detect the expressions of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex of mice in the three groups.Twelve C57BL/6J mice were randomly divided into a control group and an intervention group.The intervention group received a week of PBM interventions and underwent behavioral testing.WB was used to detect the expression changes of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex in both groups.Immunofluorescence assay was adopted to detect the expression of c-Fos in the hippocampus of mice in the two groups.The ATP assay kit made by Beyotime Biotechnology Co.,Ltd.was used to measure changes in ATP contents in the hippocampus and prefrontal cortex tissues of mice.Cell experiments were conducted to verify the effect of PBM on intracellular ATP contents.Results Mice in the stress group covered a similar distance to the control group,but finished far fewer platform crossings.There was no significant difference between the treatment group and the control group in the number of times of platform crossings,but compared favorably with the stress group where the levels of adenosine receptors in the hippocampus and prefrontal cortex were lower,but were increased by PBM.After PBM interventions in normal mice,platform crossings were increased significantly compared to the control group.PBM also raised adenosine receptor levels and ATP contents in the hippocampus and prefrontal cortex,and increased hippocampal c-Fos expressions.In vitro,PBM elevated intracellular ATP levels.Conclusion PBM may improve chronic stress-induced cognitive dysfunction by regulating ATP levels and adenosine receptor expressions,thereby modulating neuronal responsiveness in the hippocampus.

Objective:To investigate differentially expressed lipid molecules and their associated metabolic pathways in lung tissue using lipidomic analysis in a rat model of acute lung injury (ALI).Methods:An ALI rat model was established via intratracheal instillation of lipopolysaccharide (LPS). Twenty rats were randomly allocated into an ALI group and a control group ( n = 10 per group). The left lung was subjected to histopathological evaluation, while the right lung underwent untargeted lipidomics analysis. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for lipid profiling. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were performed to assess intergroup differences and determine variable importance in projection (VIP) scores. Differential lipids were screened based on VIP and fold change.Lipid identification and metabolic pathway analysis were conducted using MetaboAnalyst 5.0 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results:Among 1 022 detected lipid molecules, 47 were differentially expressed (VIP > 1, FC > 2.0 or < 0.5, P< 0.05). Subsequent analysis identified 12 structurally annotated lipids ( P < 0.05), predominantly enriched in glycerophospholipid metabolism, linoleic acid metabolism, and α-linolenic acid metabolism pathways. Notably, phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs) exhibited significant alterations in the ALI group. Conclusions:The ALI model demonstrated substantial dysregulation of lipid metabolism, particularly involving PCs and LPCs, with prominent perturbations in glycerophospholipid metabolism. This provides a scienctific basis for indepth research on the pathogenesis mechanism of ALI/acute respiratory distress syndrome (ARDS) .

OBJECTIVE To explore the effects of Tianma xiongling zhixuan tablet on autophagy in vascular endothelial cells of rats and its potential mechanism. METHODS The rat aortic endothelial cells （RAECs） were divided into normal group， model group， blank serum group， traditional Chinese medicine （TCM） medicated serum group， autophagy blocker group， autophagy agonist group， and TCM combined with autophagy agonist group. Except for normal group， other groups were given 10 μg/mL lipopolysaccharide for 24 hours to induce RAECs inflammation injury model. Blank serum group was treated with 10% blank serum； TCM medicated serum group received 10% medicated serum derived from Tianma xiongling zhixuan tablet； autophagy blocker group was treated with 20 μmol/L of PD98059； autophagy agonist group was administered 50 μmol/L Honokiol. Lastly， the TCM combined with autophagy agonist group was given both 10% medicated serum derived from Tianma xiongling zhixuan tablet and 50 μmol/L Honokiol. The morphological characteristics of RAECs in each group were observed. The cell viability of each group， the contents of endothelin-1 （ET-1） and nitric oxide （NO）， mitochondrial reactive oxygen species， mitochondrial membrane potential， and the expression levels of PTEN-induced kinase 1 （PINK1）， Parkin， ubiquitin-binding protein （p62）， and microtubule-associated protein 1 light chain 3 （LC3） were detected. RESULTS Compared with model group， the levels of ET-1， mitochondrial reactive oxygen species， and the relative expressions of PINK1， Parkin， and LC3 proteins in the autophagy blocker group and TCM medicated serum group were decreased or down-regulated significantly （P＜0.05 or P＜0.01）； the cell viability rate （only autophagy blocker group）， NO level， mitochondrial membrane potential， and the E-mail：46164660@qq.com relative expression level of p62 protein were increased or up-regulated significantly （P＜0.05 or P＜0.01）； the pathological damage of RAECs was significantly improved， the number of cells increased significantly， and the typical paving stone-like characteristics were restored. The levels of ET-1， mitochondrial reactive oxygen species， and the relative expression levels of Parkin and LC3 proteins in the autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while cell viability rate was decreased significantly （P＜0.05）， the damage of RAECs was aggravated. Compared with the autophagy agonist group， the cell viability rate and the relative expression level of p62 protein in TCM combined autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while the levels of ET-1， the relative expression levels of PINK1， Parkin， and LC3 proteins were down-regulated significantly （P＜ 0.01）， the damage of RAECs was reversed to a certain extent. CONCLUSIONS Tianma xiongling zhixuan tablet protects vascular endothelial function by regulating mitochondrial autophagy， the mechanism of which may be associated with the regulation of PINK1/Parkin signaling pathway and the inhibition of mitochondrial autophagy.

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 related functional mechanism of Xihuang pill containing serum inter-vention in breast cancer cells based on microRNA(miR)21-5p targeting FAM13A gene.Methods Bioinfor-matics websites was used to predict potential miRNAs of FAM13A gene,double luciferase reporter experi-ments were conducted to verify the binding site relationship between FAM13A and predicted miRNAs.The Xihuang pill containing serum was prepared,and human breast cancer MDA-MB-231 cells were cultured.The proliferation of MDA-MB-231 cells was interfered by the Xihuang pill containing serum with different dilution ratios by CCK-8 test,and the best dilution ratio concentration of Xihuang pill containing serum to inhibit the proliferation of breast cancer cells was selected.Real time fluorescence quantitative PCR(RT-qPCR)was ap-plied to detect the relative expression levels of FAM13A mRNA,as well as the relative expression levels of miR21-5p,in MDA-MB-231 cells after intervention with Xihuang pill containing serum.Cell proliferation(Edu)assay and cell apoptosis detection(TUNEL)assay were used to detect the effects of Xihuang pill con-taining serum intervention on cell proliferation and apoptosis function in MDA-MB-231 cells.The siRNA lentiviral transfection on MDA-MB-231 cells was performed to knock down the FAM13A gene,and Edu assay and TUNEL assay were used to detect changes in proliferation and apoptosis ability of MDA-MB-231 cells af-ter lentiviral transfection.The expression level of miR21-5p in MDA-MB-231 cells after FAM13A gene knock-out was detected by RT-qPCR technology.Results Target Scan online website predicted the potential miR-21-5p binding sequence in the 3'UTR of FAM13A mRNA,and dual luciferase reporter assay confirmed the in-teraction between miR-21-5p and FAM13A.After intervention of MDA-MB-231 cells with Xihuang pill drug containing serum,RT-qPCR results showed that compared with the control group(NC group),the Xihuang pill drug containing serum group(XHW group)downregulated the expression levels of FAM13A mRNA(P＜0.05),and upregulated the expression level of miR21-5p(P＜0.05).Compared with the NC group,the XWH group showed reduced cell proliferation ability and promoted cell apoptosis.(P＜0.05).After silencing the FAM13A gene in MDA-MB-231 cells,compared with the control group(shCtrl group),the shFAM13A group showed a significant decrease in cell proliferation ability and promoted cell apoptosis.The RT-qPCR re-sults showed that compared with the shCtrl group,the expression level of miR21-5p was significantly upregu-lated in the shFAM13A group(P＜0.05).Conclusion Xihuang pill could participate in the anti-tumor treat-ment of breast cancer by regulating miR21-5p to affect the expression level of FAM13A gene.

Breast cancer is one of the most common malignant tumors among women worldwide, with an increasing incidence rate year by year, making it a significant public health concern. With the continuous advancement of tumor biology research, N 6-methyladenosine (m 6A) modification, as an important form of RNA modification, has attracted growing attention. The m 6A modification, the most prevalent RNA modification in eukaryotes, occurs in almost all types of RNA and plays a critical role in the occurrence, progression, and metastasis of breast cancer. It influences cell proliferation, apoptosis, and alterations in the tumor microenvironment, though the specific mechanisms underlying these effects require further in-depth investigation. Moreover, the specific patterns of m 6A modification demonstrate its potential as a novel biomarker for breast cancer, which could provide new directions for early diagnosis and prognosis evaluation.

N6-methyladenosine (m6A) modification, as a widespread and high-profile type of epigenetic modification, can dynamically and reversibly regulate the whole process of RNA metabolism. This modification governs RNA stability, splicing, and translation via m6A regulators, which are categorized as Writers, Erasers, and Readers. m6A modification also plays a critical role in the development of tumors. Disruptions in the homeostasis of m6A modification levels lead to dysregulation of m6A regulators. Consequently, these dysregulated regulators modulate the proliferation, migration, and invasion of tumor cells and interfere with the normal functions of suppressor genes and oncogenes. This article aims to comprehensively elucidate the specific regulatory impacts of m6A modification on tumor-related gene expression. It focuses on the regulatory mechanisms of m6A modification on mRNA stability. Additionally, it explores the influence of m6A on the molecular translation of key signaling pathways. Moreover, it investigates the indirect regulatory effects mediated by non-coding RNAs (ncRNAs), etc. The intention is to offer a novel analysis of the pathogenesis of cancer at a new level, and also provide a theoretical basis for finding new effective treatment methods.

Objective:To establish a model for the combined detection of serum copeptin and inflammatory markers in acute stroke (AS), and to explore the value of copeptin and inflammatory marker detection in the clinical diagnosis and prognosis assessment of AS.Methods:A total of 75 patients were diagnosed with acute ischemic stroke (AIS) [46 males, age (64.1±11.7) years] and 45 patients with acute intracerebral hemorrhage (ICH) [28 males, age (61.0±13.9) years] who were admitted to the First Affiliated Hospital of Hunan University of Chinese Medicine through the emergency department from January 1 to July 31, 2024, were included as the observation group. Meanwhile, 60 healthy individuals [39 males, age (64.4±8.2) years] were selected as the control group (HC). The differences in serum copeptin levels and inflammatory markers among different groups were compared. ROC curves were drawn to analyze the value of copeptin and inflammatory markers in the clinical diagnosis and prognosis assessment of AIS. The Kaplan-Meier method was used to draw survival curves to analyze the in-hospital survival rates of patients in different groups. Cox regression analysis was conducted to identify the risk factors affecting the prognosis of AIS patients.Results:The level of copeptin was significantly elevated in AS, with the results showing ICH>AIS>HC ( H=100.11, P<0.001). Copeptin demonstrated the highest efficacy in the early diagnosis of AIS and ICH (AUC=0.893, sensitivity 89.3%, specificity 75.0%; AUC=0.986, sensitivity 95.6%, specificity 93.3%) and the assessment of prognosis (AUC=0.997, sensitivity 100%, specificity 96.8%; AUC=0.907, sensitivity 86.7%, specificity 86.7%), outperforming other single indicators. The combined detection of copeptin with the neutrophil-to-lymphocyte ratio (NLR) and the systemic immune-inflammation index (SIIRI) was the best combination for the early diagnosis of AIS and ICH (AUC=0.937, sensitivity 77.3%, specificity 98.3%; AUC=0.989, sensitivity 95.6%, specificity 95.0%) and for the assessment of prognosis (AUC=0.996, sensitivity 100%, specificity 96.8%; AUC=0.944, sensitivity 86.7%, specificity 90.0%). Kaplan-Meier survival curves showed that AIS patients in the low-value group of copeptin and NLR had a higher survival rate during hospitalization than those in the high-value group ( HR 54.46, 7.608, P<0.01, respectively), and ICH patients in the low-value group of copeptin, SIIRI, SIRI, and SII had a higher survival rate during hospitalization than those in the high-value group ( HR 12.67, 7.923, 3.567, 5.925, P<0.05); Cox regression showed that copeptin, NLR, NIHSS, and mRS were independent risk factors affecting the prognosis of patients with AIS ( HR 1.421, 1.368, 1.158, and 1.188, respectively, P<0.05), copeptin and SIIRI were independent risk factors affecting the prognosis of ICH ( HR 1.308, 1.113, P<0.05), and GCS was a protective factor affecting ICH prognosis ( HR=0.741, P<0.05). Conclusion:Copeptin and inflammatory indicators can reflect the severity of different subtypes of stroke. The single or combined detection shows good value in the clinical application of AS. The combination of copeptin-NLR and copeptin-SIIRI is respectively the best comprehensive biomarker combination for the early diagnosis and prognosis assessment of AIS and ICH.