Patients with Takayasu arteritis combined with aortic valve disease often have a poor prognosis following surgical valve replacement, frequently encountering complications such as perivalvular leakage, valve detachment, and anastomotic aneurysm. This article presents a high-risk case wherein severe aortic valve insufficiency associated with Takayasu arteritis was successfully managed through transcatheter aortic valve implantation via the transapical approach. The patient had satisfactory valve function with no complications observed during the six-month postoperative follow-up. This case provides a minimally invasive and feasible alternative for the clinical management of such high-risk patients.

Climate change is altering the Earth's water cycle system. The resulting three extreme weather events—heatwaves, droughts, and extreme precipitation—impacts urban and rural water security through multi-layered mechanisms. A primary structural disparity exists between urban and rural systems: while urban areas benefit from comprehensive and standardized pipe networks that ensure terminal water quality, rural areas often suffer from "last mile" vulnerability due to inadequate infrastructure and outdated purification facilities. Extreme weather can directly alter the microbial community structure, concentrations of chemical pollutants and physicochemical properties of source water. These alterations interfere with the efficiency of water treatment processes and ultimately compromise the integrity of distribution systems. Because distribution networks often lack real-time monitoring and adaptive response capabilities, they have emerged as the most vulnerable link in the "water source-water treatment-distribution system" chain. Based on a systematic analysis of these chain-wide impacts, this paper proposed a series of control strategies, including security frameworks based on multi-model coupling and water source protection measures, improvement of water treatment technologies, optimization of distribution systems, and development of new water quality monitoring methods. These strategies aim to enhance the climate adaptability of urban and rural drinking water systems through multi-dimensional intervention, providing a theoretical basis for constructing climate-resilient water infrastructure.

OBJECTIVE To investigate the effect and potential mechanism of toosendanin in enhancing the antileukemic activity of cytosine arabinoside against acute myeloid leukemia （AML） based on the mammalian target of rapamycin complex 1 （mTORC1） signaling pathway.METHODS Female NSG immunodeficient mice were used to establish an AML model via a single γ-ray irradiation followed by a single tail-vein injection of a U937 cell suspension. The effects of cytosine arabinoside （2.5 mg/kg）， toosendanin （1.0 mg/kg）， and cytosine arabinoside+toosendanin （2.5 mg/kg+1.0 mg/kg） on body weight， survival time， peripheral blood routine indicators， histopathological morphology， and the expressions of autophagy-related proteins were explored. Using U937 cells as the subject， the effects of cytosine arabinoside （1 μmol/L）， toosendanin （160 nmol/L）， and cytosine arabinoside+toosendanin （1 μmol/L+160 nmol/L） on the expressions of autophagy-related proteins， mTORC1 signaling pathway-related proteins and mRNAs were investigated. The targeting relationship between toosendanin and the selective autophagy ligand 1 （also known as p62） was validated， and the Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses， as well as molecular docking， were performed. A p62 -knockdown U937 stable cell line was constructed， and the underlying mechanism of toosendanin-induced sensitization was verified.RESULTS Animal experiments confirmed that the combination of toosendanin and cytosine arabinoside significantly improved body weight， survival time and peripheral blood routine indicators in AML mice （ P ＜0.05）， alleviated pathological changes such as leukemic cell infiltration and focal necrosis in bone marrow， liver， and spleen tissues， and modulated the expressions of autophagy-related proteins. Cell experiments confirmed that toosendanin could reverse cytosine arabinoside-induced activation of the autophagy cascade （manifested by downregulation of the protein expressions of microtubule-associated protein 1 light chain 3B and Beclin-1， upregulation the protein expression of p62）， and might inhibit the expression of the downstream Unc-51-like autophagy activating kinase 1 （ULK1） complex （including ULK1， ULK2， autophagy-related protein 13， and FAK family interacting protein of 200 kDa） by activating the mTORC1 signaling pathway （ P ＜0.05）. The sensitizing effect of toosendanin was associated with the inhibition of autophagy and the regulation of the mTORC1 signaling pathway； it could stably bind to p62 via hydrophobic interactions. Mechanism verification experiments indicated that upon p62 knockdown， toosendanin was no longer able to activate the mTORC1 signaling pathway or inhibit autophagy.CONCLUSIONS Toosendanin may enhance chemo-sensitivity of AML cells to cytosine arabinoside by directly targeting the p62 protein， which subsequently activates the mTORC1 signaling pathway， and thereby suppresses cytosine arabinoside-induced protective autophagy.

Objective To study the level of fall-related self-awareness among the elderly in community and to explore the influence of cognitive reserve and social cohesion on fall-related self-awareness,thereby providing a reference for developing targeted interventions.Methods Toally 500 old people in communities were recruited by convenience sampling in Hengyang between August and September 2024.Data were collected with the general information questionnaire,neighbourhood cohesion scale,self-awareness of falls in elderly scale,and cognitive reserve index questionnaire.Hierarchical multiple linear regression analysis was employed to explore the effects of cognitive reserve and social cohesion on fall-related self-awareness while controlling for demographic variables.Results A total of 467 valid questionnaires were returned.The score of fall-related self-awareness was 54.60±6.64(moderate level).Social cohesion scores was 29.84±5.52(moderate level),and cognitive reserve score was 93.27±10.83(moderate level).The cognitive reserve and social cohesion were both positively correlated with fall-related self-awareness(all P<0.01).Community integration accounted for 9.10%of its total variability,and cognitive reserve accounted for 5.70%of the total variability of fall vigilance,while controlling for variables such as body mass index(BMI),sleep quality,sedentary habits,fear of falling and financial resources.Conclusion The elderly in communities exhibit a low level of fall-related self-awareness.More attention to risk of falling is required along with developing targeted and individualised training programs aiming at improvement of cognitive reserve and social cohesion,thereby reducing the incidence of falls.

Objective To explore the clinical efficacy of evolocumab combined with bare metal stents in treating stenosis at the vertebral artery ostium and its impact on restenosis.Methods A retrospective analysis was conducted on 81 patients with ostial vertebral artery stenosis undergo-ing implantation of bare mental stents in our department from January 2022 to May 2024.Based on postoperative lipid-lowering regimens,they were divided into a statin group(51 cases,atorvas-tatin alone)and a combination group(30 cases,atorvastatin combined with evolocumab).All pa-tients were followed up for 6 months postoperatively,the changes in low-density lipoprotein cho-lesterol(LDL-C)level(△LDL-C)and total cholesterol(TC)level(△TC)as well as the rate of vascular restenosis(△restenosis rate)were compared between the two groups.Results After treatment,the combination group had significantly lower LDL-C and TC levels than the statin group(P＜0.01).The △LDL-C and △TC levels were obviously higher(1.85±1.01 mmol/L vs 1.18±0.68 mmol/L,P=0.001;1.64±0.94 mmol/L vs 1.19±0.67 mmol/L,P=0.018),and the△restenosis rate was notably lower(13.3％vs 35.3％,P=0.032)in the combination group than the statin group.Conclusion Combined evolocumab and metal bare stents demonstrates good effi-cacy in treating stenosis at the origin of the vertebral artery,and can effectively lower lipid levels and helps to reduce the occurrence of vascular restenosis.

Aim To investigate the role and regulatory mechanism of CREB regulated transcription coactivator 2(CRTC2)in cardiomyocyte hypertrophy.Methods A pathological cardiomyocyte hypertrophy model was established in C57BL/6 mice by intraperitoneal injection of isoproterenol(ISO),the expression of CRTC2 in cardiac tissue was detec-ted by Western blot.The CRTC2 knockout mice model was constructed,the cardiac function of mice was detected by small animal echocardiography,the collagen fiber content in mice cardiac tissue was detected by Masson staining,the car-diomyocyte hypertrophy related proteins:skeletal muscle α1-actin(ACTA1)and brain natriuretic peptide(BNP),as well as ferroptosis related proteins:acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in mice cardiac tissue were detected by Western blot,the iron ion content in mice cardiac tissue was detected by iron ion kit,to evaluate the correlation between CRTC2 and cardiomyocyte hypertrophy and ferroptosis.H9c2 cells were induced by ISO to construct an in vitro model of cardiomyocyte hypertrophy,the protein expressions of CRTC2,ACTA1,BNP,ACSL4,SLC7A11 and GPX4 were detected after intervention with fer-roptosis inhibitor ferrostatin-1(Fer-1).H9c2 cells with CRTC2 overexpression induced by ISO were used to construct an in vitro model of cardiomyocyte hypertrophy,the related indicators of cardiomyocyte hypertrophy and ferroptosis were detec-ted to explore the mechanism of CRTC2 in cardiomyocyte hypertrophy.Results Compared with the control group,the expression of CRTC2 protein in the cardiac tissue of ISO induced cardiomyocyte hypertrophy mice was increased(P＜0.05).Compared with wild-type mice,CRTC2-/-mice showed worsened cardiac function,manifested as increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPWT),heart weight/tibia length(HW/TL)and heart weight/body weight(HW/BW),decreased short axis shortening(FS)and ejection fraction(EF),increased collagen fiber content in cardiac tissue,upregulated ex-pression of cardiomyocyte hypertrophy-related proteins ACTA1 and BNP,increased mRNA and protein expression of ferrop-tosis-related protein ACSL4,decreased mRNA and protein expression of SLC7A11 and GPX4,and elevated iron ion content in cardiac tissue(P＜0.05 or P＜0.01).In vitro experiments showed that compared with ISO group,the ISO+Fer-1 group had no significant change in CRTC2 protein expression(P＞0.05),the expression of ACTA1 and BNP protein decreased,the surface area of cardiomyocyte reduced,the expression of ACSL4 protein decreased,and the expression of SLC7A11 and GPX4 proteins increased(P＜0.05 or P＜0.01).Compared with the ISO group,the LV-CRTC2+ISO group showed a decrease in surface area of cardiomyocytes(P＜0.01),a decrease in ACTA1,BNP and ACSL4 protein ex-pression,an increase in SLC7A11 and GPX4 protein expression,and a decrease in ROS and iron ion content(P＜0.05 or P＜0.01).Conclusion CRTC2 alleviates cardiomyocyte hypertrophy and protect cardiac function by suppressing fer-roptosis in cardiomyocytes.

Objective To investigate the influence of remifentanil infusion at different speed on propofol injection pain.Methods Totally 200 patients who accepted elective surgery under general anesthesia with tracheal intubation were selected.The patients were divided into C group,R2 group,R3 group,R4 group and R5 group by random number table method,with 40 patients in each group,and they were injected with remifentanil at a constant rate of 0 μg·kg-1·min-1,0.2 μg·kg-1·min-1,0.3 μg·kg-1·min-1,0.4 μg·kg-1·min-1,and 0.5 μg·kg-1·min-1,respectively.After 2 minutes of remifentanil infusion,a target controlled infusion of propofol at an effect-site concentration of 2.5 μg/mL was initiated.The incidence of propofol injection pain,the severity of injection pain,heart rate and mean arterial pressure before remifentanil infusion and before tracheal intubation were compared among the 5 groups.The incidence of complications such as hypotension,bradycardia and chest wall stiffness of patients was recorded.Results The incidence and the severity of propofol injection pain of patients in R2 group,R3 group,R4 group and R5 group were significantly lower than those in C group(P<0.05).The incidence of propofol injection pain of patients in R4 group was significantly lower than those in R2 group and R3 group,and the severity of propofol injection pain of patients in R4 group was significantly lower than that in R2 group(P<0.05).The incidence and the severity of propofol injection pain of patients in R5 group was significantly lower than those in R2 group and R3 group(P<0.05).However,there were no statistically significant differences in the incidence or severity of injection pain between R2 group and R3 group,and between R4 group and R5 group(P>0.05).None of the patients in each group had complications such as hypotension,bradycardia,decreased pulse oxygen saturation,and chest wall stiffness that required drug treatment.And there was no adverse reactions such as pain,edema,redness at the injection site occurred within 24 hours after operation.Conclusion Remifentanil infused at a constant rate of 0.4 μg·kg-1·min-1 and 0.5 μg·kg-1·min-1 starting at 2 minutes before propofol administration is effective in reducing propofol injection pain without causing serious complications.

BACKGROUND:Exosomes have been confirmed to be closely related to cartilage degeneration in osteoarthritis.However,the role and mechanism of exosome-derived genes in cartilage degeneration of osteoarthritis have not been fully elucidated.OBJECTIVE:Bioinformatics analyses were used to screen the genes related to cartilage degeneration in the synovial exosomes of patients with osteoarthritis,and to determine their biological functions and signaling pathways in order to provide new therapeutic targets for delaying cartilage degeneration in osteoarthritis.METHODS:Firstly,osteoarthritis-related exosome dataset GSE185059 and cartilage degeneration dataset GSE114007 were downloaded from Gene Expression Omnibus(GEO)database to screen exosome-derived cartilage degeneration related genes.GO functional and KEGG pathway enrichment analyses were performed based on the screened exosome-derived cartilage degeneration related genes.Protein-protein interaction network was drawn and Ingenuity Pathway Analysis(IPA)was conducted to screen and obtain key exosome-derived cartilage degeneration-related genes.Finally,qRT-PCR was used to verify the expression of key genes in osteoarthritis cartilage tissue and interleukin-1β stimulated chondrocyte models.RESULTS AND CONCLUSION:(1)There were 831 differentially expressed genes in the GSE185059 dataset and 5 323 differentially expressed genes in the GSE114007 dataset.A total of 94 exosome-derived cartilage degeneration related genes were screened after the intersection of these differentially expressed genes,of which 51 genes were down-regulated and 43 genes were up-regulated.(2)GO functional enrichment analysis showed that the up-regulated genes were mainly involved in the positive regulation of cell-cell adhesion,the positive regulation of T cell activation,and chronic inflammatory response,while the down-regulated genes were mainly involved in biological processes such as cell aggregation,cartilage differentiation and development,and skeletal system morphogenesis.(3)KEGG pathway enrichment analysis showed that exosome-derived cartilage degeneration-related genes were mainly involved in tryptophan enrichment metabolism,vitamin B6 metabolism,and leukocyte transendothelial migration.(4)The constructed protein-protein interaction network confirmed the existence of multiple interaction relationships among exosome-derived cartilage degeneration-related genes.Combined with five algorithms in CytoHubba software,four key exosome-derived cartilage degeneration-related genes were further screened,namely THY1,CYP1A1,NFKB2,and COL6A3.(5)The results of qRT-PCR showed that compared with normal cartilage,the expressions of THY1 and COL6A3 in osteoarthritic cartilage were increased,while the expression of CYP1A1 and NFKB2 was decreased.Similarly,compared with the unstimulated group,the expression of THY1 and COL6A3 in the interleukin-1β induced chondrocytes was upregulated,while the expression of CYP1A1 and NFKB2 was downregulated.(6)These results indicate that THY1,CYP1A1,NFKB2,and COL6A3 are genes related to cartilage degeneration in the exosomes of synovial fluid of patients with osteoarthritis,and may participate in the pathogenesis of osteoarthritis by regulating biological processes such as protein tyrosine kinase activity and lipid metabolism,as well as nuclear factor-κB signaling pathway and focal adhesion signaling pathway.However,the specific regulatory roles and molecular mechanisms of these key genes in cartilage degeneration need to be further verified by experiments.

AIM To evaluate the quality of Rubi Fructus.METHODS UPLC-Q-TOF-MS/MS was adopted in the component identification,after which the HPLC fingerprints were established,cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition.and the contents of chlorogenic acid,ferulic acid,ellagic acid,isoquercitrin,kaempferol-3-O-rutinoside,astragalin,tiliroside quercetin,kaempferol were determined.RESULTS Total 34 constituents were identified.There were 19 common peaks in the fingerprints for 31 batches of medicinal materials with the similarities of more than 0.8.Wild varieties and cultivated varieties,and medicinal materials from different producing areas could be distinguished;4 principal components demonstrated the accumulative variance contribution rate of 84.142％;8 differential components were screened,2 of which were ellagic acid and astragalin.Ellagic acid and astragalin displayed higher contents in the wild varieties than those in the cultivated varieties(P＜0.05,P＜0.01).CONCLUSION UPLC-Q-TOF-MS/MS,HPLC fingerprints combined with content determination can be used for the quality control of Rubi Fructus.

AIM:To investigate the protective ef-fect of osthole(Ost)on APAP-induced liver injury in mice and its molecular mechanism.METHODS:We established the APAP-induced liver injury model in mice,and Ost was used to intervene.The expres-sion of AST,ALT,SOD,ROS,MDA,LDH,GSH-PX in mice plasma were detected by biochemical meth-od.HE staining was used to observe the changes of liver tissue structure.Immunofluorescence assay was used to detect the expression of Tif1γ and Smad4 in liver tissue.The mRNA expression of IL-1β,IL-6,TNF-α,Smad4,and Tif1γ were detected by qRT-PCR.Western blot was applied to assess the protein expression of Smad2/3 and pSmad2/3 in liver tissue.RESULTS:Compared with the control group,the liver structure destruction and hepato-cyte death was increased,ALT,AST,ROS,MDA and LDH were increased,while SOD and GSH-PX were decreased,and the mRNA expressions of IL-1β,IL-6 and TNF-α were increased in the model group.Compared with the model group,the Ost interven-tion group had improved liver structure and de-creased liver cell death;decreased ALT,AST,ROS,MDA and LDH,increased SOD and GSH-PX,and de-creased expression of IL-1β,IL-6 and TNF-α mRNA.Compared with the control group,liver tissues of model mice showed increased expression of pS-mad2/3,Smad4 protein and Smad4 mRNA,and de-creased Tif1γ protein and mRNA.Compared with the model group,the liver tissues of the Ost inter-vention group showed decreased expression of pS-mad2/3,Smad4 protein and Smad4 mRNA,and in-creased expression of Tif1γ protein and mRNA.CONCLUSION:Ost can improve liver function,re-duce oxidative stress and inflammatory reaction,and protect hepatocyte damage induced by APAP in mice,which may be related to the up-regulation of Tif1γ and inhibition of TGF-β1/Smad signaling pathway.