Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMP-activated protein kinase(AMPK)activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis(MASH).Rhizoma Atractylodis Mac-rocephalae(RAM)has been clinically used to treat obesity-related health problems,but its therapeutic effects on MAFLD and the underlying mechanism remain unclear.Therefore,this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.Methods:The effect of RAM decoction on MAFLD was evaluated using a high-fat diet(HFD)-induced MAFLD mouse model.In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum.The underlying mechanisms were elucidated through a combination of network pharmacology analysis,immunohis-tochemistry,western blotting,and polymerase chain reaction analysis.Results:Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake.The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment.Additionally,RAM administration decreased serum levels of alanine aminotrans-ferase,aspartate transaminase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,and glucose,while reducing lipid droplet accumulation in the liver tissues of MAFLD mice.The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase(ACC),and inhibition of the expression of sterol regulatory element binding protein 1(SREBP1).However,RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α.Furthermore,the RAM-induced upregulation of phosphorylated AMPK,phos-phorylated ACC,and SREBP1 expression,as well as the downregulation of fatty acid synthase expression,were reversed by using an AMPK inhibitor.Conclusions:Through a combination of network pharmacology and experimental validation,we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.

Objective To explore the pathogenesis of Alzheimer's disease by examining the effects of dihydroartemisinin(DHA)on cognitive behavior,hippocampal,cerebral cortex and retinal cell morphology,β-amyloid(Aβ)and autophagy-related proteins in 5×FAD mice.Methods Twenty 5×FAD mice and 5 wild type(WT)mice were selected,all of which were female.The 5×FAD mice were randomly divided into model(M)group,donepezil(D)group,low-dose DHA(DHA-L)group,and high-dose DHA(DHA-H)group.The WT and M groups were not treated,and the D group was given donepezil 0.1 mg/kg per day.DHA-L group and DHA-H group were given 10 mg/kg and 20 mg/kg DHA per day,respectively.Group D,group DHA-L and group DHA-H were given intragastric administration once a day for 3 months.The changes of in cognitive behavior were measured by Morris experiment.HE staining was used to observe the arrangement and morphology of nerve cells in cerebral cortex,hippocampus and retina.The expressions of Aβ protein in cerebral cortex,hippocampus and retina were detected by immunohistochemistry.Western blotting detected the expression of autophagy related proteins(LC3-Ⅰ,LC3-Ⅱ,Beclin-1,P62,β-actin).Results The DHA-H group and the D group exhibited more frequent adoption of both linear and trending exploration routes.Compared to the model group,significant differences in the contents of Aβ in the hippocampal CA1,cerebral cortex S1,and retinal were observed(P＜0.0001)in the other four groups.The analysis also showed significant differences in autophagy-associated proteins between the DHA-L,DHA-H,and model groups(P＜0.01).Conclusion DHA improves cognitive function and increases the number of nerve cells in mice.It also reduces Aβ content in the cerebral cortex,hippocampus,and retina,along with improving autophagy-associated protein deposition in mice.

Objective:To investigate the diagnostic and prognostic value of systemic immune inflammatory index (SII) for severe traumatic brain injury secondary to acute lung injury (sTBI-ALI).Methods:A retrospective study was conducted on patients with severe traumatic brain injury admitted to the trauma center of the First Affiliated Hospital of Soochow University from January 2021 to November 2023. Patients received standard treatments including hemostasis and intracranial pressure management. Vital signs and blood routine data were collected upon admission. Patients were categorized into sTBI group and sTBI-ALI group based on established clinical diagnostic criteria for ALI to evaluate the diagnostic utility of SII. Subsequently, within the sTBI-ALI group, patients were stratified into survival and non-survival groups based on their 30-day outcomes to assess the prognostic value of SII.Results:A total of 260 sTBI patients were enrolled, of whom 113 developed ALI. Among the sTBI-ALI patients, 73 survived at 30 days. Compared to the sTBI group, the sTBI-ALI group exhibited significantly higher respiratory rates, heart rates, white blood cell counts, neutrophil counts, platelet counts, and SII levels (all P<0.05). Multivariate logistic regression analysis showed that SII index ( OR=1.003, 95% CI: 1.002-1.004, P<0.001) was an independent risk factor for ALI development in sTBI patients. The combined predictive model incorporating SII and heart rate yielded an AUC of 0.801 (95% CI: 0.740-0.862). The non-survival group had significantly higher neutrophil counts and SII levels, and significantly lower Glasgow Coma Scale scores than the survival group (all P<0.05). Multifactorial regression analysis indicated that SII index ( OR=1.002, P=0.004, 95% CI: 1.000-1.003) served as an independent risk factor for 30-day mortality in sTBI-ALI patients. The combined predictive model of SII and GCS achieved an AUC of 0.904 (95% CI: 0.848-0.960). Conclusions:SII demonstrates potential as a biomarker for predicting the development of ALI following sTBI. Furthermore, incorporating SII into predictive models significantly enhances the ability to forecast mortality risk in sTBI-ALI patients.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

AIM To investigate the clinical effects of Cinobufosin Injection combined with RALOX-HAIC regimen on patients with hepatocellular carcinoma.METHODS Ninety-two patients were randomly assigned into control group(46 cases)for intervention of RALOX-HAIC regimen,and observation group(46 cases)for intervention of both Cinobufosin Injection and RALOX-HAIC regimen.The changes in short-term effects,survival situation,inflammatory indices(LCN2,NLRP3 inflammasome,NLR,PLR),immune indices(NK cells,CD8+T cells,IL-17,Th17/Treg)and incidence of toxic and side effects were detected.RESULTS Based on mRECIST,the observation group demonstrated higher disease control rate and objective remission rate than the control group(P＜0.05),along with lower disease progression(P＜0.05).After the treatment,the two groups displayed decreased inflammatory indices,IL-17,Th17/Treg(P＜0.05),and increased NK cells,CD8+T cells(P＜0.05),especially for the observation group(P＜0.05).The observation group exhibited lower incidence of abdominal pain,nausea,vomiting,diarrhea,leukopenia and thrombocytopenia than the control group(P＜0.05),and no significant differences in overall survival and incidence of other toxic and side effects were found between the two groups(P＞0.05).CONCLUSION For the patients with hepatocellular carcinoma,Cinobufosin Injection combined with RALOX-HAIC regimen can safely and effectively enhance body immune functions,and reduce in vivo immune indices.

Plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in the environment are important"fingerprint"nuclides in the study of nuclear activity traceability.The content of plutonium isotopes in the environmental metrics is usually very low,and the measurement of these isotopes,especially 238Pu,using mass spectrometry is seriously interfered with by the coexisting 238U.The analysis of several plutonium isotopes in soil usually requires combination of multiple measurement techniques,which leads to a long analysis time and large uncertainty in the isotope ratio.In this work,the hydrous titanium oxide(HTiO)precipitated by the hydrolysis of titanium oxydichloride(TiOCl2)under near-neutral condition was used to preconcentrate plutonium from the soil digestion solution,and the highly efficient decontamination of 238U in the sample was achieved by TK200 resin column chromatography with a decontamination factor of 108.Simulation resuts of density functional theory(DFT)showed that NH3 was considered as a promising reaction gas to eliminate the interference of 238U from 238Pu measurement using mass spectrometry due to the significant discrepancy of the chemical reactivity of U+and Pu+with the reactive gas NH3.Experiments confirmed that by optimizing the flow rates of collision gas(He)and reaction gas(NH3),the interference of 238U could be effectively suppressed,and the decontamination factor of 238U was 104.Combined with chemical separation,the overall decontamination factor of 238U could reach 1012 by using the developed method.By combining chemical separation and tandem quadrupole inductively coupled plasmon-mass spectrometry(ICP-MS/MS)measurement,the simultaneous determination of four ultra-trace plutonium isotopes in soil was realized,and the detection limit of plutonium isotopes was at the femtogram level.Analysis of the international standard reference materials(NIST-SRM-4357 and IAEA-384)showed that the established method could be successfully used for the accurate analysis of ultra-trace four plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in soil samples.

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

Objective To analyze the characteristics of TCM symptoms of aging in female insomnia patients;To provide syndrome differentiation evidence for clinical prevention and treatment of female aging.Methods A cross-sectional study method was used to include female insomnia patients who attended outpatient clinics at Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing Changping District Hospital of Traditional Chinese Medicine,and the Third Affiliated Hospital of Beijing University of Chinese Medicine from August 2021 to July 2024.The patients'clinical information was collected,and frequency analysis,factor analysis,and clustering analysis of the relevant clinical information of the 107 female insomnia patients were conducted,which,together with the experts'opinions,resulted in characteristics of TCM syndrome elements and syndrome distribution of aging in female insomnia patients.Results Totally 20 core items were screened and 7 common factors were obtained from the factor analysis.There were 5 types of syndrome elements of disease location associated with aging symptoms in female patients with insomnia,including heart,liver,spleen,kidney and lung;and there were 7 types of syndrome elements of disease property,including qi deficiency,yin deficiency,qi stagnation,blood deficiency,heat,phlegm,and dampness.There were 4 types of syndromes were obtained from the systematic clustering,including heart-kidney disharmony syndrome,heart-liver stagnation syndrome,spleen deficiency and qi stagnation syndrome,lung-spleen qi deficiency syndrome.Conclusion By analyzing the TCM syndrome characteristics of aging symptoms in female patients with insomnia,four types of syndromes are obtained.The heart-kidney disharmony syndrome is the common syndrome.The internal relationship between insomnia and aging process in female patients with insomnia is revealed from the perspective of pathogenesis,which can provide a research basis for the clinical practice of TCM anti-aging guided by syndrome differentiation and treatment in the future.

Objective:To investigate the role of platelet-derived zyxin in promoting tumor migration by platelets.Methods:The gene expression profile of platelets was analyzed from cancer patients by using the GEO database.Isolated platelets from wild-type(WT)and Zyx-/-mice were co-cultured with B16F10 cells labeled with green fluorescence to investigate the influence of zyxin deficiency on tumor cell migration,invasion,and wound healing.Optical microscopy was employed to evaluate the impact of zyxin deficiency on epithelial-mesenchymal transition(EMT)in B16F10 cells induced by platelets.Employing specific markers to label platelets,fluorescence confocal microscopy was utilized to investigate the impact of platelet-derived zyxin on the binding between tumor cells and platelets.And an aggregometer was employed to observe the influence of zyxin deficiency on tumor cell-induced platelet aggregation.Results:Compared to platelets from healthy volunteers,zyxin was upregulated in platelets from cancer patients.Zyx-/-mouse platelets exhibited a significant reduction in tumor cell invasion and migration,impaired wound healing,and delayed tumor cell EMT compared to WT mouse platelets.Additionally,zyxin deficiency attenuated the interaction between platelets and tumor cells,and diminished the capacity for tumor cell-induced platelet aggregation.Conclusion:Platelet-derived zyxin deficiency diminishes platelet-tumor cell interactions and weakens the ability of tumor cell-induced platelet aggregation,ultimately suppressing tumor cell migration.

Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.