ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Objective:To evaluate the clinical rehabilitation effect of external counterpulsation(ECP)on patients with coronary heart disease(CHD)by meta-analysis.Methods:We searched the databases of CNKI,WanFang,VIP,CBM,PubMed,Web of Science,Cochrane Library and Embase for randomized controlled trials(RCTs)and prospective cohort studies upon rehabilitative effect of ECP on CHD patients before May 2024.And meta-analysis was conducted to calculate the pooled MD and 95％CI using the random(P＜0.5 or I2≥50％)or fixed effect models(other situations).Results:13 eligible literatures were finally included in the meta-analysis.Compared with participants in control group,those in trial group had significant higher left ventricular ejection fraction(MD=4.15,95％CI 2.55～5.76,P＜0.001),stroke volume(MD=9.11,95％CI 7.59～10.64,P＜0.001),peak oxygen uptake(MD=5.42,95％CI 2.53～8.32,P＜0.001),6-min walking distance(MD=31.14,95％CI 24.89～37.40,P＜0.001),metabolic equiv-alent(MD=0.58,95％CI 0.45～0.71,P＜0.001),exercise duration time(SMD=0.77,95％CI 0.55～0.99,P＜0.001),oxygen pulse(MD=0.88,95％CI 0.68～1.09,P＜0.001),and significant lower left ventricular end-diastolic diameter(MD=-3.19,95％CI-5.20～-2.61,P＜0.001).Conclusion:This study showed that ECP could effectively improve heart function,exercise capacity and tolerance of CHD patients.

Indocyanine green(ICG)is one of the near-infrared fluorescent contrast agents approved for clinical use in fluorescence-guided surgery.Although widely applied,it still has some limitations.In recent years,various targeted fluorescent agents have been explored in pancreatic cancer patients;however,there is still no standardized consensus among surgeons regarding fluorescence-guided surgery for pancreatic cancer.In 2023,the first the international consensus report on fluorescent surgery navigation for pancreatic tumors was published,gathering perspectives from 38 pancreatic surgeons worldwide on current practices and future directions.A total of 76 statements were anonymously voted on using the Delphi method,resulting in 61 recommended statements.This consensus offers valuable guidance for the implementation of fluorescence-guided surgery in pancreatic tumor operations in China,yet its clinical application should be adapted in consideration of local expert opinions and patient-specific factors.This article interprets key aspects of the consensus,including the use of ICG,intraoperative fluorescence imaging techniques,and the fluorescence heterogeneity of pancreatic tumors,in combination with the authors'clinical experience,with the aim of providing reference and insight for the application of fluorescence-guided surgery in pancreatic tumors.

Objective To explore the safety of establishing the veno-arterial extracorporeal membrane oxygenation(VA-ECMO)pipeline through percutaneous puncture and the effectiveness of high-risk percutaneous coronary intervention(HR-PCI)under VA-ECMO assistance.Methods In this single-center retrospective study,patients who underwent HR-PCI assisted by VA-ECMO at Wuhan Asian Heart Hospital from December 2022 to December 2023 were included.The primary endpoint was the safety of establishing the VA-ECMO pipeline through percutaneous puncture,mainly characterized by extracorporeal membrane oxygenation(ECMO)-related complications,including severe bleeding/hematoma at the wound,arteriovenous fistula,pseudoaneurysm,peripheral arterial dissection,etc.The secondary endpoint was the effectiveness of HR-PCI under VA-ECMO assistance,defined as major adverse cardiovascular and cerebrovascular events(MACCE)at 6-month follow-up,including the composite events of all-cause death,non-fatal myocardial infarction,repeat revascularization,and ischemic stroke.Results Among the 189 patients included in the study,15(7.9％)had severe bleeding/hematoma at the puncture wound caused by VA-ECMO,8(4.2％)had wound infection,1(0.5％)had arteriovenous fistula,4(2.1％)had pseudoaneurysm,3(1.6％)had peripheral arterial dissection,8(4.2％)had systemic embolism,8(4.2％)had acute kidney injury,3(1.6％)had acute neurological injury,and 1(0.5％)died.percutaneous coronary intervention(PCI)was successful in 182 cases(96.3％),and a total of 36 cases(19.0％)had PCI-related complications.164 patients completed 6-month follow-up,among which 4(2.4％)had all-cause death,11(6.7％)had non-fatal myocardial infarction,11(6.7％)had unplanned repeat revascularization,and 2(1.2％)had the composite event of ischemic stroke.Conclusions Ultrasound-guided percutaneous puncture for establishing the VA-ECMO pipeline has high safety,and HR-PCI patients assisted by VA-ECMO have good short-term effects.

Patients with advanced pregnancy complicated by acute ST-segment elevation myocardial infarction are relatively rare both domestically and internationally,and there are currently no relevant guidelines to guide clinical treatment.In this case,a 39-year-old pregnant woman was admitted to the hospital with sudden chest pain,and the electrocardiogram showed extensive anterior ST-segment elevation myocardial infarction.Coronary angiography showed subtotal subtotal occlusion of the proximal left anterior descending artery.Reperfusion and revascularization were given,and the blood flow grade of the trial of thrombolytic in myocardial infarction was restored.Complete intravascular ultrasonography to determine the cause of occlusion due to spontaneous hematoma of the left anterior descending artery.After the operation,a reasonable antiplatelet and anticoagulant treatment regimen was selected according to the coronary artery lesion,and the pregnancy was terminated at the appropriate time,and 1 live male baby was successfully delivered.Maternal and fetal health was followed up after 1、3 and 6 months.Through the experience and summary of the treatment process,combined with the literature,the pathogenesis of this disease is discussed,and the strategy of revascularization,the selection of antithrombotic drugs and the timing of pregnancy termination are discussed in depth for clinical reference.

Objective:To explore the early predictive value of the triglyceride-glucose (TyG) index and the controlling nutritional status (CONUT) score for severe acute pancreatitis (SAP).Methods:Clinical data from 1 050 hospitalized patients with acute pancreatitis (AP) at the General Hospital of Central Theater Command between January 2019 and December 2023 were retrospectively analyzed. Patients were categorized into mild acute pancreatitis (MAP) group ( n=606), moderately severe acute pancreatitis (MSAP) group ( n=320), and SAP group ( n=124) based on AP severity. General clinical data, laboratory parameters, modified computed tomography severity index (MCTSI), bedside index for severity in acute pancreatitis (BISAP), TyG index, and CONUT score were compared among the three groups. Spearman correlation analysis was used to evaluate the relationship between TyG index, CONUT score and AP severity. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for AP severity. Receiver operating characteristic curves (ROC) were plotted to calculate the area under the curve (AUC), sensitivity, and specificity for evaluating the predictive efficacy of TyG index, CONUT score, and their combination for SAP. Results:Significant differences on TyG index and CONUT score were observed among AP patients with varying severity (all P value <0.001). Spearman correlation analysis further revealed positive correlations of TyG index ( r=0.174), CONUT score ( r=0.306) with AP severity (both P<0.001). Multivariate logistic regression identified neutrophil count ( OR=1.076, 95% CI 1.027-1.125), MCTSI ( OR=2.565, 95% CI 2.250-2.921), BISAP ( OR=3.522, 95% CI 2.726-4.549), TyG index ( OR=1.859, 95% CI 1.276-2.707), and CONUT score ( OR=1.155, 95% CI 1.035-1.288) as independent risk factors for AP severity. The combined predictive model equation was: -7.342+0.76×TyG+0.439×CONUT. ROC analysis showed that the AUC values of the TyG index, CONUT score, and the combined index (TyG index+CONUT score) were 0.583 (95% CI 0.529-0.637), 0.701 (95% CI 0.652-0.75), and 0.755 (95% CI 0.710-0.801), with sensitivities of 0.706, 0.677, and 0.742, and specificities of 0.884, 0.629, and 0.657, respectively (all P value <0.05). Conclusions:TyG index and CONUT score are positively correlated with AP severity and may serve as reliable predictors for SAP. Their combination could enhance the predictive accuracy for AP.

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 explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.