Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Children with cancer represent a distinct patient population, and decisions regarding hospice care preferences are primarily made by their parents. This article examines parental preferences concerning the location and goals of hospice care for their children with cancer, discusses the advantages and disadvantages associated with these choices, and identifies factors influencing parental preferences for hospice care. The aim is to provide a reference for clinical healthcare professionals in delivering high-quality hospice care services for children with cancer that align with parental preferences.

Objective To construct a prediction model for in-hospital mortality in the elderly(≥65 years)patients undergoing unsynchronous cardioversion in ICU and to evaluate its effectiveness.Methods A retrospective study was conducted on 276 elderly eligible patients in the ICU of the Ninth and the First Medical Centers of Chinese PLA General Hospital between June 2022 and August 2024.According to their clinical outcomes,they were divided into a non-in-hospital dead group(111 cases)and an in-hospital dead group(165 cases).Clinical data were collected,and pre-dictive factors for in-hospital mortality were screened.And then a nomogram prediction model was developed based on the obtained predictive factors,which was evaluated with ROC curve and deci-sion curve analyses.Results When compared to the non-in-hospital dead group,the in-hospital dead group had significantly higher heart rate,ratio of hemodialysis,and levels of alanine amin-otransferase,aspartate aminotransferase,lactate dehydrogenase,alkaline phosphatase,serum cre-atinine,blood glucose,lactate,low base excess,sequential organ failure assessment(SOFA)score,model for end-stage liver disease score,and larger proportions of ventricular fibrillation/flutter and structural heart disease induced by pulseless ventricular tachycardia,and had significantly lower Glasgow Coma Scale(GCS)(P＜0.05).Multivariate logistic regression analysis identified body temperature＞37℃(OR=0.426,95％CI:0.198-0.915,P=0.029),chronic obstructive pulmonary disease(OR=2.333,95％CI:1.217-4.473,P=0.011),GCS score(OR=0.622,95％CI:0.410-0.944,P=0.026),hemoglobin(OR=0.817,95％CI:0.715-0.934,P=0.003),lactate(OR=1.365,95％CI:1.174-1.587,P=0.000),heart rate＞100 bpm(OR=2.757,95％CI:1.397-5.441,P=0.003),and SOFA score(OR=1.112,95％CI:1.032-1.198,P=0.005)as pre-dictors of in-hospital mortality.ROC curve analysis showed an AUC value of above indicators combined together in the prediction was 0.797,with a sensitivity of 76.97％and a specificity of 65.77％.Calibration curve analysis demonstrated good consistency between predicted and observed outcomes.Decision curve analysis indicated favorable clinical utility of the model.Conclusion This study identifies independent risk factors for in-hospital mortality among elderly patients in the ICU who underwent asynchronous cardioversion.Based on these factors,a nomo-gram model is established,demonstrating good discrimination,calibration,and model fit,with high clinical applicability.

Objective To analyze the correlation between right atrial strain at various stages and various influencing factors in patients with pulmonary hypertension,and to explore the role of right atrial strain in the assessment of pulmonary hypertension.Methods A total of 239 cases diagnosed with pulmonary hypertension who underwent echocardiography and complete right heart catheterization at hospital from October 2021 to December 2023 were included.Conventional ultrasound parameters such as right heart strain,right atrial area(RA area),inferior vena cava diameter(IVC diameter),and collapse rate of the inferior vena cava(IVC diameter changes)were measured.The heart rate(HR)corresponding to the ultrasound images were recorded.General information such as age and gender,as well as catheter data including mean right atrial pressure(mRAP),mean pulmonary artery pressure(mPAP),and pulmonary vascular resistance(PVR),were collected.The relationship between right atrial strain and its influencing factors was analyzed,and further analysis was conducted by dividing into shunt group and non-shunt group based on the presence or absence of left-to-right shunt disease.Results The correlation with RA reservoir strain(RASr)from high to low is RV global strain(RV4CSL),RV free wall strain(RVFWSL),RA area,IVC diameter,mRAP,age,HR,and PVR;the correlation with RAconduit strain(RAScd)from high to low is RV4CSL,RVFWSL,RA area,IVC diameter,mRAP,age,PVR,and HR;the correlation with RA contraction strain(RASct)from high to low is RA area,RV4CSL,RVFWSL,mRAP,IVC diameter,and HR.The collapse rate of the inferior vena cava is correlated with strain at various stages of the right atrium;gender is correlated with RASr and RASct.Conclusions Right atrial strain can reflect changes in right atrial function,with the highest correlation to right ventricular strain and right atrial area.Right atrial strain can indicate the severity of right ventricular function and right atrial remodeling,serving as an evaluative index for the condition and treatment outcomes of pulmonary arterial hypertension.

The MGF300-4L protein of African swine fever virus(ASFV),a virulence-associated fac-tor,degrades IKKβ through the chaperone-mediated autophagy and enhances the stability of IKBαto suppress the generation of IL-1β and TNF-α regulated by the NF-κB signaling pathway.To iden-tify the host proteins interacting with MGF300-4L,PK-15 cells were transfected with the eukary-otic plasmid expressing MGF300-4L and analyzed using immunoprecipitation-mass spectrometry(IP-MS)to identify the host proteins that interact with MGF300-4L.Additionally,gene ontology(GO)and KEGG pathway enrichment analyses were conducted.Furthermore,molecular docking a-nalysis,co-immunoprecipitation,and laser confocal microscopy assays were performed to validate the host proteins interacting with MGF300-4L.The IP-MS analysis identified 145 host proteins that potentially interact with MGF300-4L.Subsequent GO and KEGG pathway enrichment analy-ses revealed that these proteins are predominantly involved in metabolic,cellular,and innate immune responses.Through molecular docking prediction,co-immunoprecipitation assay,and laser confocal microscopy,we identified the interaction between MGF300-4L and STAT1.This study provides critical insights into the mechanisms underlying the interactions between MGF300-4L and the host proteins.

Objective To compare the serological and pathological characteristics of 3 nonalcoholic steatohepatitis(NASH)models:high-fat diet(HFD)with carbon tetrachloride(CCl4)injection,methionine and choline deficient diet(MCD),and Aymlin liver NASH(AMLN)diet-induced NASH models.Methods 3 NASH models were established by feeding mice an HFD with CCl4 injection for 10 weeks,MCD for 8 weeks and NASH for 26 weeks.After feeding,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),glucose(GLU),liver triglyceride(TG),total cholesterol(TC),and malondialdehyde(MDA)levels and superoxide dismutase(SOD)activity were measured.Insulin levels were measured by enzyme-linked immunosorbent assay(ELISA)and the homeostasis model assessment of insulin resistant(HOMA-IR)index was calculated.Hematoxylin-eosin(HE),Sirius red,and oil red staining were used to indicate pathological changes to the liver.The NAS score was used to grade the pathology.Results Compared to each normal control(NC)group mice,all mice in the 3 model groups had an obvious increase in serum transaminase and liver TG,TC,MDA levels and SOD activity.The levels of serum FINS,GLU and the HOMA-IR index were significantly increased in the AMLN and CCl4+HFD model groups but decreased in the MCD model group.According to the HE,oil red staining and NAS score,mice in all 3 groups had NASH phenotypic changes.Liver collagen deposition was most obvious in mice in theCCl4+HFD model group.Liver lipid droplets were most abundant in the AMLN model group.Conclusions All the above 3 animal models can stably simulate the serological and pathological changes of NASH in human.The AMLN model can simulate the progress and mechanism of the disease,as well as systemic metabolic disorders such as insulin resistance and oxidative stress.However,it is time-consuming and the fibrosis progression rate is slow.The MCD diet can simulate the serological and pathological features of NASH in 8 weeks,but no obesity or insulin resistance occurred.The CCl4 combined with HFD model can induce NASH model in 10 weeks,which can simulate its serological and pathological changes,and the liver has obvious fibrous deposition and oxidative stress damage.

Objective To analyze the expression level of triggering receptor expressed on myeloid cells-1(TREM-1)in serum and ascites of patients with cirrhotic ascites,and to investigate its correlation with clinical features and inflammatory markers and its role in the diagnosis of infection and prognostic evaluation.Methods A total of 110 patients with cirrhotic ascites who were hospitalized in The Fifth Hospital of Shijiazhuang from January 2019 to December 2020 were enrolled,and according to the presence or absence of intra-abdominal infection,they were divided into infection group with 72 patients and non-infection group with 38 patients.The patients with infection were further divided into improvement group with 38 patients and non-improvement group with 34 patients.Clinical data and laboratory markers were collected from all patients.Serum and ascites samples were collected,and ELISA was used to measure the level of TREM-1.The independent-samples t test was used for comparison of normally distributed continuous data between two groups;the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups,and the Kruskal-Wallis H test was used for comparison between multiple groups;the chi-square test was used for comparison of categorical data between two groups.A Spearman correlation analysis was used to investigate the correlation between indicators.A multivariate Logistic regression analysis was used to identify the influencing factors for the prognosis of patients with cirrhotic ascites and infection.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic and prognostic efficacy of each indicator,and the Delong test was used for comparison of the area under the ROC curve(AUC).Results The level of TREM-1 in ascites was significantly positively correlated with that in serum(r=0.50,P<0.001).Compared with the improvement group,the non-improvement group had a significantly higher level of TREM-1 in ascites(Z=-2.391,P=0.017)and serum(Z=-2.544,P=0.011),and compared with the non-infection group,the infection group had a significantly higher level of TREM-1 in ascites(Z=-3.420,P<0.001),while there was no significant difference in the level of TREM-1 in serum between the two groups(P>0.05).The level of TREM-1 in serum and ascites were significantly positively correlated with C-reactive protein(CRP),procalcitonin(PCT),white blood cell count,and neutrophil-lymphocyte ratio(r=0.288,0.344,0.530,0.510,0.534,0.454,0.330,and 0.404,all P<0.05).The ROC curve analysis showed that when PCT,CRP,and serum or ascitic TREM-1 were used in combination for the diagnosis of cirrhotic ascites with infection,the AUCs were 0.715 and 0.740,respectively.The multivariate Logistic regression analysis showed that CRP(odds ratio[OR]=1.019,95%confidence interval[CI]:1.001-1.038,P=0.043)and serum TREM-1(OR=1.002,95%CI:1.000-1.003,P=0.016)were independent risk factors for the prognosis of patients with cirrhotic ascites and infection,and the combination of these two indicators had an AUC of 0.728 in predicting poor prognosis.Conclusion The level of TREM-1 is closely associated with the severity of infection and prognosis in patients with cirrhotic ascites,and combined measurement of TREM-1 and CRP/PCT can improve the diagnostic accuracy of infection and provide support for prognostic evaluation.

Widespread utilization of glyphosate has led to environmental residues,posing potential threats to ecological systems and human health.Traditional methods for detection of glyphosate are limited by specialized equipment and operational techniques,resulting in inefficient responses.Therefore,it is urgent to develop a convenient,sensitive and accurate detection method for detection of glyphosate.Herein,a new naphthalenesulfonamide-based"Turn-on"fluorescent probe was synthesized using 2-chloroaniline and dansyl chloride as raw materials through a one-step process,which showed a good linear relationship between the glyphosate concentration in concentration range of 0.003-70 μmol/L and the fluorescence intensity(R2=0.995),with a detection limit of 2.73 nmol/L(S/N=3).Analytical techniques such as nuclear magnetic resonance(NMR)spectroscopy and high-resolution mass spectrometry(HRMS)were used to investigate the interaction mechanism between the fluorescent probe and glyphosate.The results indicated that a nucleophilic substitution reaction occurred between the probe and the secondary amine(—NH—)of glyphosate,inducing a photoinduced electron transfer(PET)effect which enhanced the fluorescence intensity by 11.2 times.The probe showed good anti-interference ability towards coexisting metal ions,anions and pesticides in water.When applied to determination of glyphosate in the samples such as tap water,river water(Xiangxi River Reservoir),soil,soybeans,and corn,the spiking recoveries ranged from 94.7％to 109.9％,demonstrating the high accuracy and broad applicability of this detection method.A portable test strip based on this fluorescent probe was developed for rapid semi-quantitative analysis of glyphosate.The developed method was rapid,sensitive,and portable,providing theoretical and technical support for on-site measurement of environmental contaminants.

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*