A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective To analyze the correlation between lesion volume,lesion mass,and maximum lesion diameter in the assessment of advanced hepatocarcinoma with lung metastasis,and to evaluate the application value of total volume response and total mass response of lung metastatic lesions in efficacy assessment.Methods A retrospective analysis was conducted on the CT imaging data of 20 patients clinically confirmed with hepatocarcinoma and lung metastases,followed by subsequent follow-up to monitor their survival outcomes.Volume measurement software was used to measure the volume of lesions before and after treatment.We recored lesion diameter,volume measurements and CT values,calculated the mass of the lesions.The correlation between lesion volume,mass and diameter was analyzed,as well as the correlation between the change rates of volume,mass and lesion diameter.Additionally,the total volume and total mass of all lesions were calculated.The correlation between the change rates of total volume/total mass and the change rate of pulmonary lesion diameter under the RECIST 1.1 criteria,as well as the correlation with changes in patients'tumor markers,were analyzed.Furthermore,the overall volume response and overall mass response of lesions were evaluated based on changes in total volume and total mass,and their consistencies with the RECIST 1.1 criteria for efficacy evaluation were analyzed.Finally,univariate Cox regression analysis was performed to explore the association between these variables and patient survival outcomes.Results There was strong correlation between lesion volume,mass and tumor diameter(r=0.771,0.775),between the rate of change in mass and the rate of change in lesion diameter(r=0.846),and between the rates of change in total volume/total mass and the rate of change in pulmonary lesion diameter under the RECIST 1.1 criteria(r=0.800,0.896).The correlation between the rates of change in total volume/total mass and patients'tumor markers was not statistically significant.There was moderate correlation between the rate of change in volume and the rate of change in lesion diameter(r=0.692).The evaluation results of total volume response and total mass response for pulmonary lesions in advanced hepatocarcinoma with lung metastasis were generally consistent with the RECIST 1.1 criteria(Kappa=0.486,0.426).Univariate Cox regression analysis revealed that total lesion volume(P=0.047)and total lesion mass(P=0.049)were independent prognostic factors for survival outcomes.Conclusion Lesion volume,mass,and diameter,as well as their respective change rates,were found to be interrelated.Furthermore,total lesion volume and total lesion mass were identified as independent prognostic factors for survival outcomes.The total volume response and total mass response are promising evaluation methods in evaluating the efficacy of lung metastasis of hepatocarcinoma,which are different from the RECIST 1.1 evaluation criteria.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.

Objective:To prepare nanoscale docetaxel-loaded lipid microbubbles(DLLM),characterize their physical and chemical properties,evaluate their biosafety and anti-tumor effects in vitro,and explore their potential as a targeted delivery system for chemotherapeutic drugs.Methods:DLLM was prepared by thin film hydration method.The morphology,particle size and distribution were characterized by transmission electron microscopy,scanning electron microscopy and particle size analyzer.The drug encapsulation efficiency was determined by high performance liquid chromatography.Human hepatoma HepG2 cells were used as a model to set up the control group(Control group),the docetaxel group(DOC group),the docetaxel-loaded lipid microbubbles group(DLLM group)and the docetaxel-loaded lipid microbubbles+ultrasound group(DLLM+US group).The cell morphology was observed by optical microscope,the cell survival rate was detected by CCK-8 method,and the apoptosis was detected by flow cytometry.The biocompatibility of microbubbles and their mediated ultrasound-enhanced anti-tumor effect were evaluated.Results:The prepared DLLM was regular spherical,with a particle size distribution range of 200-600 nm,an average particle size of 380 nm,and an encapsulation efficiency of 80.3％±2.6％.The cell viability of the DOC group and the DLLM+US group was significantly lower than that of the Control group(P＜0.01),and the apoptosis rate was significantly increased(P＜0.01).The cell viability of the DLLM+US group was lower than that of the DOC group(P＜0.05),and the apoptosis rate was higher than that of the DOC group(P＜0.05).There was no significant difference in cell viability and apoptosis rate between the DLLM group and the Control group(P＞0.05).Conclusions:The nano-scale DLLM prepared in this experiment has uniform particle size,high encapsulation efficiency,good stability and biocompatibility.DLLM can enhance the killing and pro-apoptotic effects of docetaxel on HepG2 cells under ultrasound irradiation.

Objective To observe the clinical efficacy and safety of vericiguat tablets combined with sacubitril valsartan sodium(Sac/Val)tablets in the treatment of patients with heart failure with reduced ejection fraction(HFrEF).Methods The HFrEF patients were divided into control group and treatment group according to the cohort method.The control group was treated with Sac/Val tablets 200 mg per time,bid,orally.On the basis of control group,the treatment group was treated with vericiguat tablets 2.5 mg per time,qd,taken with meal.Two groups were treated for 3 months.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic dimension(LVEDD)and end-systolic diameter(LVESD),levels of high sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6),nitric oxide(NO),N-terminal pro-brain natriuretic peptide(NT-proBNP),blood urea nitrogen(BUN)and serum creatinine(SCr),and safety were compared between the two groups.During follow-up,the heart failure rehospitalization rates and major adverse cardiovascular events were compared between the two groups.Results Treatment group was enrolled 53 patients,control group was enrolled 53 patients.After treatment,the total effective rates of treatment and control groups were 94.34％(50 cases/53 cases)and 81.13％(43 cases/53 cases)with statistical significant difference(P＜0.05).After treatment,the LVEF of treatment and control groups were(48.02±5.20)％and(43.02±4.33)％,the LVEDDs were(52.85±6.30)and(55.63±6.88)mm,the LVESDs were(41.64±6.40)and(44.22±5.85)mm,the levels of hs-CRP were(10.22±2.63)and(14.60±2.98)mg L-1,the levels of IL-6 were(14.48±2.40)and(17.36±2.52)pg·mL-1,the levels of NO were(102.60±20.16)and(92.16±16.33)μmol·L-1,the levels of NT-proBNP were(898.74±102.20)and(1315.60±182.64)ng·L-1,the levels of BUN were(12.02±2.28)and(13.45±2.33)mmol·L-1,the levels of SCr were(82.22±5.89)and(85.64±6.03)μmol·L-1,the heart failure rehospitalization rates were 5.66％and 13.21％,respectively;the differences were statistical significant between two groups(all P＜0.05).The adverse drug reactions of treatment group were hyperkalemia,hypotension,renal dysfunction,dizziness and headache,while those in control group were renal dysfunction,hyperkalemia,and hypotension.The major adverse cardiovascular events of treatment group were angina pectoris and acute myocardial infarction,while those in control group were angina pectoris,acute myocardial infarction and atrial fibrillation.The incidences of total adverse drug reactions in treatment and control groups were 13.21％and 7.55％,the incidences of major adverse cardiovascular events were 5.66％and 13.21％,respectively,without statistically significant differences(all P＞0.05).Conclusion Vericiguat tablets combined with Sac/Val tablets have a definitive clinical efficacy in the treatment of HFrEF patients,which can improve cardiac and endothelial function,reduce inflammatory response and readmission times,without increasing the incidences of adverse drug reactions.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.

Objective:To prepare nanoscale docetaxel-loaded lipid microbubbles(DLLM),characterize their physical and chemical properties,evaluate their biosafety and anti-tumor effects in vitro,and explore their potential as a targeted delivery system for chemotherapeutic drugs.Methods:DLLM was prepared by thin film hydration method.The morphology,particle size and distribution were characterized by transmission electron microscopy,scanning electron microscopy and particle size analyzer.The drug encapsulation efficiency was determined by high performance liquid chromatography.Human hepatoma HepG2 cells were used as a model to set up the control group(Control group),the docetaxel group(DOC group),the docetaxel-loaded lipid microbubbles group(DLLM group)and the docetaxel-loaded lipid microbubbles+ultrasound group(DLLM+US group).The cell morphology was observed by optical microscope,the cell survival rate was detected by CCK-8 method,and the apoptosis was detected by flow cytometry.The biocompatibility of microbubbles and their mediated ultrasound-enhanced anti-tumor effect were evaluated.Results:The prepared DLLM was regular spherical,with a particle size distribution range of 200-600 nm,an average particle size of 380 nm,and an encapsulation efficiency of 80.3％±2.6％.The cell viability of the DOC group and the DLLM+US group was significantly lower than that of the Control group(P＜0.01),and the apoptosis rate was significantly increased(P＜0.01).The cell viability of the DLLM+US group was lower than that of the DOC group(P＜0.05),and the apoptosis rate was higher than that of the DOC group(P＜0.05).There was no significant difference in cell viability and apoptosis rate between the DLLM group and the Control group(P＞0.05).Conclusions:The nano-scale DLLM prepared in this experiment has uniform particle size,high encapsulation efficiency,good stability and biocompatibility.DLLM can enhance the killing and pro-apoptotic effects of docetaxel on HepG2 cells under ultrasound irradiation.

Objective To propose a preventive maintenance strategy of the heating,ventilation and air-conditioning(HVAC)system in pharmacy intravenous admixture services(PIVAS)based on the reliability centered maintenance(RCM)method so as to provide references for PIVAS equipment maintenance.Methods Firstly,a HVAC system RCM review team was formed,and the failure modes and impacts of important functional components of the equipment were analyzed to clarify the consequences of the failure of each functional component under the premise of ensuring the safety and integrity of the equipment and with the goal of minimizing the loss of maintenance downtime and the consumption of maintenance resources.Secondly,with a standardized logical decision-making procedure the preventive maintenance strategy was determined and implemented based on the consequences of functional failure.Finally,statistical analyses were carried out on such equipment indicators as performance parameter qualification rate,failure rate and maintenance cost before and after the RCM method-based strategy was executed,in order to evaluate the efficacy of the strategy.Results The RCM method-based preventive maintenance strategy had the performance qualification rate increased from 97.47%to 99.06%(χ2=24.139,P<0.01),the failure rate decreased from 0.24%to 0.03%(χ2=13.519,P<0.01)and the maintenance cost reduced by 11.5%,from RMB 134,200 to 118,700.Conclusion The RCM method-based preventive maintenance strategy provides reliable equipment for PIVAS and lowers the maintenance cost effectively,and references are given for the development of automated and intelligent equipment maintenance strategies for PIVAS.[Chinese Medical Equipment Journal,2025,46(10):78-83]