This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Objective To evaluate the effect of Intravascular lithotripsy(IVL)in the treatment of calcified nodules,and to observe the presence of coronary dissection after IVL treatment.Methods A total of 106 patients with coronary atherosclerotic heart disease(coronary heart disease)admitted to the cardiovascular Department of Shougang Hospital,Peking University from March 2023 to July 2024 were retrospectively analyzed.A total of 106 patients with moderate to severe stenosis accompanied by calcification as detected by coronary angiography were treated with IVL after intravascular ultrasound(IVUS)examination.Patients were divided into two groups according to whether there were calcified nodules in the coronary lesions:39 cases in the calcified nodules group and 67 cases in the non-calcified nodules group.The occurrence of coronary dissection during surgery was observed between the two groups,and other perioperative related complications and major adverse cardiovascular events(MACE)within 1 month after percutaneous coronary intervention(PCI)were compared between the two groups.Results The levels of renal insufficiency(25.6％vs.9.0％,P=0.021)and creatinine[(119.71±134.75)μmol/L vs.(71.82±16.53)μmol/L,P=0.033]in the calcified nodule group were higher than those in the non-calcified nodule group,the difference was statistically significant,and there was no difference in other baseline data.The target vessels in the calcified nodule group were mainly left anterior descending branch and right coronary artery,while those in the non-calcified nodule group were mainly left anterior descending branch,with few circumflex branches in both groups,and there was statistical significance in the distribution of target vessels in the left anterior descending branch and right coronary artery between the two groups(P=0.020).In terms of eccentric calcification(P=0.048)and asymmetric calcification(48.7％vs.28.4％,P=0.035)between the two groups,the calcified nodule group was higher than the non-calcified nodule group,the difference was statistically significant(P＜0.05).In terms of whether more than 20 pulses were needed and whether there was slippage during IVL,the calcified nodule group was higher than the non-calcified nodule group,the difference was statistically significant(P=0.022).The success rate of interventional therapy was 100％in both groups.After IVL treatment,the calcified nodule group was higher than the non-calcified nodule group in terms of the occurrence of coronary artery dissection,the difference was statistically significant(P＜0.009).The MACE of the two groups within 1 month after PCI was slightly higher in the calcified nodule group than in the non-calcified nodule group,but the difference was not statistically significant(P=0.235).Conclusions IVL is feasible and effective for the treatment of calcified coronary nodules.However,in the course of treatment,the occurrence of coronary dissection should be vigilant,identified as early as possible,and treated in time.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

The lesion of the left main coronary artery(LM)itself is one of the challenges of interventional therapy.If the lesion is combined with calcification,the interventional therapy is difficult to operate and extremely risky.This case report presents a 77-year-old elderly male patient.Coronary angiography(CAG)indicated severe stenosis of the LM-left anterior descending(LAD)accompanied by severe calcified bifurcation lesions.After pre-dilation,percutaneous coronary intraluminal shock wave balloon catheter angioplasty(IVL)was applied for treatment.Before IVL treatment,the LM-LAD lesion was subjected to ischemic preconditioning by using an appropriate balloon to fix the pressure and gradually upgrading the balloon dilation time.Later,a Cross-over procedure was performed to implant a single stent,achieving satisfactory results.Among them,the ischemic preconditioning methods for LM lesions can provide reference significance for clinicians.

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.

This study analyzed the demographic characteristics and clinically significant inflammatory index changes in listeriosis cases in China from 2010 to 2023.The aim was to understand Listeria monocytogenes susceptibility,to provide a reference for listeriosis prevention and control.Records in three Chinese databases—the China Knowledge Network,Wanfang Database,and VIP Database—from January 1,2010,to December 31,2023,were searched.Statistical analysis was conducted on the clinical features and epidemiological information for all identified cases.A total of 693 cases of listeriosis were included:482 occurring during the perinatal period and 211 occurring outside the perinatal period.The average mortality rate was 17.2%(119/693).The predominant clinical manifestations of listeriosis in neonatal patients during the perinatal period were sepsis(75.5%,241/319)and meningitis(41.1%,131/319).The mortality rate among neonatal patients was 27.1%(76/280).In patients in the non-perinatal period,meningitis(70.1%,148/211)and sepsis(43.6%,92/211)were the main clinical manifestations,and the average patient age was 47.2 years.Among patients of known age,the highest prevalence was observed in the 40-64 year age group,which accounted for 44.9%(44/98).Sixty-one cases had no other underlying diseases before infection.Reported cases of listeriosis occurred in 27 provinces(municipalities,and autonomous region)in China,and Beijing reported the most cases,accounting for 23.7%(164/693).L.monocytogenes was sensitive to β-lactam drug treatment but showed differing degrees of drug resistance.Among 145 cases,12 were resistant to penicillin,and 16 were resistant to oxacillin.Listeriosis is a foodborne disease with a high mortality rate,particularly among neonates.With the continuing emergence of drug-resistant strains,standardizing and strengthening prevention and treatment measures for this disease as early as possible are essential.

This study analyzed the demographic characteristics and clinically significant inflammatory index changes in listeriosis cases in China from 2010 to 2023.The aim was to understand Listeria monocytogenes susceptibility,to provide a reference for listeriosis prevention and control.Records in three Chinese databases—the China Knowledge Network,Wanfang Database,and VIP Database—from January 1,2010,to December 31,2023,were searched.Statistical analysis was conducted on the clinical features and epidemiological information for all identified cases.A total of 693 cases of listeriosis were included:482 occurring during the perinatal period and 211 occurring outside the perinatal period.The average mortality rate was 17.2%(119/693).The predominant clinical manifestations of listeriosis in neonatal patients during the perinatal period were sepsis(75.5%,241/319)and meningitis(41.1%,131/319).The mortality rate among neonatal patients was 27.1%(76/280).In patients in the non-perinatal period,meningitis(70.1%,148/211)and sepsis(43.6%,92/211)were the main clinical manifestations,and the average patient age was 47.2 years.Among patients of known age,the highest prevalence was observed in the 40-64 year age group,which accounted for 44.9%(44/98).Sixty-one cases had no other underlying diseases before infection.Reported cases of listeriosis occurred in 27 provinces(municipalities,and autonomous region)in China,and Beijing reported the most cases,accounting for 23.7%(164/693).L.monocytogenes was sensitive to β-lactam drug treatment but showed differing degrees of drug resistance.Among 145 cases,12 were resistant to penicillin,and 16 were resistant to oxacillin.Listeriosis is a foodborne disease with a high mortality rate,particularly among neonates.With the continuing emergence of drug-resistant strains,standardizing and strengthening prevention and treatment measures for this disease as early as possible are essential.

The influence of material properties on fingerprint development effects were systematically studied.Firstly,carbon dots/NaYF4 and Cu nanoclusters/starch nanocomposites respectively possessing different fluorescent intensities and dual fluorescent colors,as well as NaYF4 micro-/nano-materials exhibiting different morphologies,sizes,and surface properties were chemically synthesized and further used for latent fingerprint development.Then,the developing effects were comprehensively evaluated by visual analysis combining with spectral characterization and Python-based calculation.Finally,the influences of material properties on latent fingerprint development were quantitatively evaluated from three dimensions including contrast,sensitivity,and selectivity.The fluorescence properties of developing materials and substrates could significantly affect the developing contrast,namely,the stronger the developing signal,the higher the contrast;the weaker the background noise,the higher the contrast.The sizes and morphologies of the developing materials could respectively influence the quantity and quality of developed minutiae,and significantly affect the developing sensitivity,namely,the smaller the particle size of developing materials,the more the quantity of developed minutiae and the higher the sensitivity;the smaller the surface area of developing materials,the higher the quality of developed minutiae and the higher the sensitivity.The surface properties together with the sizes and morphologies of developing materials could influence their adsorption performances,and significantly affect the developing selectivity,namely,the stronger the specific adsorption of developing materials with fingerprint substance,and the weaker the non-specific adsorption of developing materials with substrate,the higher the selectivity.Moreover,the fingerprint development using the materials with suitable surface area and appropriate mass would have a high selectivity.

OBJECTIVES: To investigate the prognostic value of molecular minimal residual disease (Mol-MRD) monitored before and after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML). METHODS: Clinical data of 71 pediatric AML patients who underwent HSCT between August 2016 and December 2023 were analyzed. Mol-MRD levels were dynamically monitored in MRD-positive patients, and survival outcomes were evaluated. RESULTS: No significant difference in the 3-year overall survival (OS) rate was observed between patients with pre-HSCT Mol-MRD ≥0.01% and <0.01% (77.3% ± 8.9% vs 80.4% ± 7.9%, P=0.705). However, patients with pre-HSCT Mol-MRD <1.75% had a significantly higher 3-year OS rate than those with Mol-MRD ≥1.75% (86.6% ± 5.6% vs 44.4% ± 16.6%, P=0.020). The median Mol-MRD level in long-term survivors was significantly lower than in non-survivors [0.61% (range: 0.04%-51.58%)] vs 10.60% (range: 1.90%-19.75%), P=0.035]. Concurrent flow cytometry-based MRD positivity was significantly higher in non-survivors (80% vs 24%, P=0.039). There was no significant difference in the 3-year overall survival rate between patients with Mol-MRD ≥0.01% and those with <0.01% at 30 days post-HSCT (P=0.527). For children with Mol-MRD <0.22% at 30 days post-HSCT, the 3-year overall survival rate was 80.4% ± 5.9%, showing no significant difference compared to those with molecular negativity (87.0% ± 7.0%) (P=0.523). CONCLUSIONS Patients with pre-HSCT Mol-MRD <1.75% or post-HSCT Mol-MRD <0.22% may achieve long-term survival outcomes comparable to Mol-MRD-negative cases through HSCT and targeted interventions.
Humans ; Hematopoietic Stem Cell Transplantation ; Neoplasm, Residual ; Leukemia, Myeloid, Acute/genetics* ; Child ; Male ; Female ; Child, Preschool ; Prognosis ; Adolescent ; Infant ; Transplantation, Homologous

OBJECTIVE: Aloin, the main active component in Aloe vera (L.) Burm. f., has shown promising anti-tumor effects. This study investigated the impact of aloin in lung squamous cell carcinoma (LUSC) and explored its functional mechanism. METHODS: We analyzed the viability, migration, invasion, proliferation, and apoptosis of two LUSC cell lines after treatment with aloin. Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2 (NR3C2) were predicted by bioinformatics. The biological functions of NR3C2 and metallothionein 1 M (MT1M) in the malignant properties of LUSC cells were determined. A co-culture system of LUSC cells with monocyte-derived macrophages was constructed. Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo. RESULTS: Aloin suppressed malignant properties of LUSC cells in vitro. However, these effects were negated by the silencing of NR3C2. NR3C2 was found to activate MT1M transcription by binding to its promoter. Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing. Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages, whereas NR3C2 silencing led to reverse trends. Consistent findings were reproduced in vivo. CONCLUSION This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization. Please cite this article as: Chen YN, Lu JY, Gao CF, Fang ZR, Zhou Y. Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis. J Integr Med. 2025; 23(2): 195-208.
Lung Neoplasms/metabolism* ; Humans ; Animals ; Cell Line, Tumor ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Macrophages/drug effects* ; Emodin/analogs & derivatives* ; Metallothionein/genetics* ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Receptors, Glucocorticoid/genetics*