The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Effective annotation of in vivo drug metabolites using liquid chromatography-mass spectrometry (LC-MS) remains a formidable challenge. Herein, a metabolic reaction-based molecular networking (MRMN) strategy is introduced, which enables the "one-pot" discovery of prototype drugs and their metabolites. MRMN constructs networks by matching metabolic reactions and evaluating MS² spectral similarity, incorporating innovations and improvements in feature degradation of MS² spectra, exclusion of endogenous interference, and recognition of redundant nodes. A minimum 75% correlation between structural similarity and MS² similarity of neighboring metabolites was ensured, mitigating false negatives due to spectral feature degradation. At least 79% of nodes, 49% of edges, and 97% of subnetworks were reduced by an exclusion strategy of endogenous ions compared to the Global Natural Products Social Molecular Networking (GNPS) platform. Furthermore, an approach of redundant ions identification was refined, achieving a 10%-40% recognition rate across different samples. The effectiveness of MRMN was validated through a single compound, plant extract, and mixtures of multiple plant extracts. Notably, MRMN is freely accessible online at https://yaolab.network, broadening its applications.

The escalating phenomenon of global population aging is posing multi-dimensional challenges to society, the economy and medical healthcare system.Among the significant health threats to the elderly population are cardiovascular diseases(CVD)and cognitive frailty(CF), both of which profoundly affect the quality of life and increase the risks of adverse health outcomes, including disability, hospitalization, and death.The concurrent presence of CVD and CF in elderly patients is prevalent, as these conditions share many common risk factors and underlying pathophysiological mechanisms, such as atherosclerosis, microcirculation dysfunction, and inflammation, which interact to perpetuate a vicious cycle.Notably, CF exhibits a certain degree of reversibility; thus, the implementation of a diagnosis and treatment paradigm that incorporates "comprehensive geriatric assessment and geriatric interdisciplinary teams" should be established as a conventional management strategy for elderly patients affected by both CVD and CF.Cognitive digital therapeutics, along with personalized exercise prescriptions based on cardiopulmonary exercise tests, may represent more appropriate precision interventions for these patients.Consequently, there is a necessity for further in-depth research in this area moving forward.

Cardiovascular diseases(CVD)are chronic disease with high morbidity and mortality in the world.Pinellia ternatais a traditional Chi-nese medicinal herb and has the effects on drying dampness,resolving phlegm,lowering symptoms,stopping vomiting and relieving swelling.In recent years,researches showed that Pinellia ternataand its active ingredients(β-sitosterol,baicalin,baica-lein,quercetin)had significant effects in the treat-ment of cardiovascular diseases.This review sum-marized and analyzed the role and mechanism of Pinellia ternata and its active ingredients in cardio-vascular diseases,which provided a theoretical ba-sis for its clinical application.

Cardiovascular diseases(CVD)are chronic disease with high morbidity and mortality in the world.Pinellia ternatais a traditional Chi-nese medicinal herb and has the effects on drying dampness,resolving phlegm,lowering symptoms,stopping vomiting and relieving swelling.In recent years,researches showed that Pinellia ternataand its active ingredients(β-sitosterol,baicalin,baica-lein,quercetin)had significant effects in the treat-ment of cardiovascular diseases.This review sum-marized and analyzed the role and mechanism of Pinellia ternata and its active ingredients in cardio-vascular diseases,which provided a theoretical ba-sis for its clinical application.

The escalating phenomenon of global population aging is posing multi-dimensional challenges to society, the economy and medical healthcare system.Among the significant health threats to the elderly population are cardiovascular diseases(CVD)and cognitive frailty(CF), both of which profoundly affect the quality of life and increase the risks of adverse health outcomes, including disability, hospitalization, and death.The concurrent presence of CVD and CF in elderly patients is prevalent, as these conditions share many common risk factors and underlying pathophysiological mechanisms, such as atherosclerosis, microcirculation dysfunction, and inflammation, which interact to perpetuate a vicious cycle.Notably, CF exhibits a certain degree of reversibility; thus, the implementation of a diagnosis and treatment paradigm that incorporates "comprehensive geriatric assessment and geriatric interdisciplinary teams" should be established as a conventional management strategy for elderly patients affected by both CVD and CF.Cognitive digital therapeutics, along with personalized exercise prescriptions based on cardiopulmonary exercise tests, may represent more appropriate precision interventions for these patients.Consequently, there is a necessity for further in-depth research in this area moving forward.

Objective To investigate whether suffering from atrial fibrillation in different ages of people increasing the onset risk of new-onset acute myocardial infarction(AMI).Methods A prospective cohort study was conducted to select 96 624 Kailuan Group employees undergoing the health examination from June 2006 to October 2007 for including the study.The participants were followed up once a year,and the last fol-low-up date was December 31,2020,with a median follow-up of 14.01 years,and the endpoint event was new-onset AMI.The participants were divided into two age groups according to the age ≥60 years and the age＜60 years old,and divided into the atrial fibrillation group and non-atrial fibrillation group according to whether they had atrial fibrillation.The epidemiological investigation and anthropometric measurements were carried out on the participates.Whether atrial fibrillation was correlated to the onset of new-onset AMI in different age groups conducted the statistical analysis.Results Among the total participants,there were 411 cases in the atrial fibrillation group and 96 213 cases in the non-atrial fibrillation group.Among the participants＜60 years old,there were 121 cases in the atrial fibrillation group and 75 151 cases in the non-atrial fibrillation group.Among the participants ≥60 years old,there were 290 cases in the atrial fibrillation group and 21 062 cases in the non-atrial fibrillation group.In the total participants,the cumulative incidence rate of AMI in the atrial fibrillation group was higher than that in the non-atrial fibrillation group(5.68％vs.1.92％),and the difference was statistically significant(P＜0.05).In the participants＜60 years old,the cumulative incidence rate of AMI in the atrial fibrillation group was higher than that in the non-atrial fibrillation group(7.40％vs.1.43％),and the difference was statistically significant(P＜0.05).In the participants 60 year old,the cu-mulative incidence rate of AMI had no statistical difference between the atrial fibrillation group and non-atrial fibrillation group(4.54％vs.3.87％,P=0.547).In the whole participants,atrial fibrillation was a risk factor for new-onset AMI(HR=1.877,95％CI:1.177-2.991,P=0.008),and there was an interaction between age and atrial fibrillation(P=0.016).In the age stratification analysis,atrial fibrillation was a risk factor for new-onset AMI in＜60-year-old population(HR=3.029,95％CI:1.508-6.082,P=0.002).Conclusion Atrial fibrillation is an independent risk factor for new-onset AMI,especially to young and middle-aged people(＜60 years old).

【Objective】 To clarify the role and molecular mechanism of Tanshinone ⅡA (TanⅡA) in the pathological integration of granule cells in the dentate gyrus (DG) by using the mouse model of temporal lobe epilepsy (TLE). 【Methods】 Status epilepticus (SE) was induced in the mice with pilocarpine and treated with TanⅡA 5 mg/kg. After two months, Morris water maze was used to examine the spatial learning and memory ability and video surveillance was used to monitor spontaneous seizures. The DG was removed for staining of Timm, Prox-1, DCX and SynⅠ. PTEN, p-AKT, and p-S6 expressions were observed by Western blotting. 【Results】 TanⅡA decreased Timm score, SynⅠ, PSD-95 and pS6 levels, and increased the level of PTEN in the DG, and attenuated the formation of mossy fiber sproutings and basal dendrites of the granule cells. Video surveillance showed that TanⅡA reduced the frequency of Racine’ grade 5 seizures. 【Conclusion】 TanⅡA can effectively attenuate the abnormal integration of the granule cells in the DG by regulating PTEN/AKT/mTOR pathway and thus plays an anti-epileptic role.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Objective: To explore the application value of virtual touch tissue imaging quantification(VTIQ) technology in initial polymyositis(PM). Methods: Sixteen PM patients collected from February 2016 to March 2019 in Wenzhou People′s Hospital were selected as PM group, and 33 healthy subjects as healthy control group. After gray and color Doppler ultrasound, the shear wave velocity(SWV) values of target muscle and control muscle in the same side of affected limb were measured by VTIQ technique. Maximum velocity(Vmax) and minimum velocity(Vmin) were measured, average velocity(Vmean) and standard deviation(SD) were calculated, and compared between the two groups. SWV difference and ratio between target muscle and control muscle were calculated, and creatine kinase(CK) was detected in the same day. Results: Part of PM patients had abnormal ultrasonographic manifestations of full muscle shape (31.25%), increased or decreased echo of muscle bundles (56.25%), blurred muscle texture (25.00%) and increased blood flow signals (37.50%). There were significant differences in Vmin, SD, and Vmax difference, Vmin difference, Vmean difference, and Vmax ratio, Vmin ratio, and Vmean ratio between PM group and healthy control group (all P<0.01). The ROC curve analysis showed that the diagnostic efficiency of Vmin was lower than those of Vmin difference and Vmean difference, Vmin ratio and Vmean ratio with very close diagnostic efficiencies of the latter four parameters. The correlation analysis showed that Vmin difference and Vmean difference were moderately correlated with CK value(r=0.512, 0.601; all P<0.05). Conclusions Reduced VTIQ values or relative reduction of VTIQ values compared with other non-involved muscles are the manifestations of initial PM, VTIQ have certain diagnostic efficacy for initial PM.