Objective: To analyze the impact of premature death due to four major chronic diseases on life expectancy in Yangpu District, Shanghai Municipality from 2010 to 2021, so as to provide the evidence for formulating chronic disease prevention and control strategies. Methods : Mortality data of registered residents in Yangpu District from 2010 to 2021 were collected through the Death Information Registration and Management System of the Shanghai Municipal Disease Control and Prevention Information Management Platform. The premature death probability of malignant tumors, diabetes, cardiovascular and cerebrovascular diseases, and chronic respiratory diseases, and life expectancy of residents were calculated using the abridged life table method. Trends in premature death probability for four types of chronic diseases were analyzed using the average annual percent change (AAPC). The impact of premature death probability due to four chronic diseases on life expectancy was assessed by Arriaga's decomposition method. Results : The premature death probability due to four major chronic diseases in Yangpu District decreased from 9.88% in 2010 to 9.22% in 2021, showing an overall declining trend (AAPC=-0.540%, P<0.05). Among females, the premature death probability declined from 6.71% to 4.90% (AAPC=-2.715%, P<0.05), whereas no statistically significant trend was observed in males (P>0.05). Life expectancy increased from 82.52 years in 2010 to 84.50 years in 2021, with an overall upward trend (AAPC=0.244%, P<0.05). Life expectancy rose by 1.71 years for males and 2.34 years for females (AAPC=0.197% and 0.303%,both P<0.05). Declines in premature death probability from malignant tumors (AAPC=-0.967%, P< 0.05) and chronic respiratory diseases (AAPC=-3.071%, P<0.05) contributed to gains in life expectancy of 0.30 years and 0.03 years, with contribution rates of 12.18% and 1.29%, respectively. Changes in premature death probability due to diabetes as well as cardiovascular and cerebrovascular diseases were not statistically significant (both P>0.05), resulting in reductions in life expectancy of 0.05 years and 0.10 years, with contribution rates of -2.40% and -5.05%, respectively. Notably, an increase in premature death probability due to cardiovascular and cerebrovascular diseases among males (AAPC=1.673%) contributed to a decrease of 0.22 years in male life expectancy, whereas a decrease among females (AAPC=-3.824%) contributed to an increase of 0.03 years in female life expectancy, with contribution rates of -13.03% and 1.14%, respectively. Conclusions From 2010 to 2021, Yangpu District experienced an overall decline in premature death probability due to four major chronic diseases and an increase in life expectancy. Greater attention should be paid to the negative impacts of premature death probability from diabetes as well as cardiovascular and cerebrovascular diseases among males on life expectancy.

An ion chromatography method was developed for detection of nine kinds of trace organic amines(Methylamine,dimethylamine,trimethylamine,ethylamine,diethylamine,triethylamine,n-propylamine,n-butylamine,and ethanolamine)and six kinds of trace water-soluble inorganic cations(Li+,Na+,NH4+,K+,Ca2+,and Mg2+)in atmospheric fine particulate matter(PM2.5)in this wok.Various chromatographic columns(IonPac CS12,IonPac CS17 and IonPac CS19)were compared in terms of their separation efficiency for target analytes,and IonPac CS19 column was ultimately selected.Through meticulous optimization of the column temperature,a low temperature condition of 20℃was found to achieve the highest separation efficiency(All are above 1),effectively separating all 15 kinds of target analytes.Under the optimal analytical conditions inculding methanesulfonic acid(MSA)as eluent,100 μL of injection volume,column temperature at 20℃and eluent at flow rate of 1 mL/min,the detection limits of this method ranged from 0.05 to 7.15 μg/L,the quantification limits were 0.16-23.82 μg/L,and the spiking recoveries were 84%-105%.The proposed method exhibited high accuracy and excellent reproducibility,and was suitable for concurrent analysis and measurement of organic amines and water-soluble inorganic cations in PM2.5.

Liquiritigenin(LG)is a flavone of pharmacological importance,however,its application potential is severely limited due to its poor water solubility.LG could be disassociated slightly in water to form phenolate anion,therefore,better solubilization effect is expected by inclusion with cationic cyclodextrins(CCDs).In this work,four kinds of CCDs modified with amino groups at the primary face were synthesized,and their solid inclusion complexes with LG were successfully prepared by preparing their saturated solutions.The formation of the solid inclusion complexes was confirmed by scanning electron microscopy(SEM)and powder X-ray diffraction(PXRD),and their supramolecular binding behavior in solution was studied using multiple techniques.A 1∶1 inclusion stoichiometry of inclusion complexation was defined using Job plot by ultraviolet-visible(UV-vis)spectroscopy,and their binding stability constants(Ks)were determined as 2862.77,3494.70,6521.85 and 9599.48 L/mol using UV-vis spectroscopic titration,far more superior to that of nativeβ-CD(Ks=236.79 L/mol).This indicated that the amino side chains on CCDs could actively participate in the inclusion complexation through anion-cation interactions,significantly strengthening the host-guest binding between CCDs and LG.The inclusion modes were further elucidated based on proton and two-dimensional rotating-frame overhauser enhancement spectroscopy(2D-ROESY)nuclear magnetic resonance(NMR)experiments and molecular docking.Water solubility of LG was dramatically promoted up to 4.9 mg/mL,which was 70-fold higher than that of native LG.This study could draw inspiration for the binding and solubilization of phenols such as flavones by design of cationic macrocyclic molecules.

Apurinic/apyrimidinic endonuclease 1(APE 1)is a multifunctional protein that plays important roles in DNA repair and regulation of gene expression.Because APE 1 is overexpressed in various cancers,it can serve as a cancer biomarker for aiding clinical diagnosis,guiding therapy,and monitoring prognosis.On this basis,a label-free fluorescent probe was designed based on the primer exchange reaction(PER)strategy for highly sensitive detection of APE 1 activity.In the absence of APE 1,the structure of catalytic hairpin(HP)was stable and could not form G-quadruplex.Therefore,the background fluorescence of this sensing system was very low due to the dissociation of thioflavin T(ThT).In the presence of APE 1,the apurinic/apyrimidinic(AP)site of HP was cleaved by APE 1 and a short nucleic acid fragment that acted as a primer to initiate PER was generated.After PER reaction,a large number of G-quadruplex were produced,which could specifically bind with ThT and resulted in significant increase of fluorescence signal.The combination of low background design of HP and PER amplification made this biosensor had high sensitivity with a detection limit(3σ)of 0.0008 U/mL.Furthermore,the primer sequence was directly generated by the cleavage of APE 1 without additional addition,which not only increased the specificity of the reaction,but also simplified the experiment procedure.Moreover,the use of label-free fluorescence signal reduced the cost of the experiment,and realized rapid detection of APE 1.Finally,this sensor was used to detect APE 1 in human serum samples with spiked recoveries of 91%-104%,proving great potential in study of biological enzyme.

The stability of ammonium ion selective electrode is an important indicator to ensure accurate monitoring of ammonia nitrogen concentration in drinking water.However,in long-term monitoring process,interfering ions and water molecules in water samples may penetrate into the interior of the ammonium ion selective electrode to form a water layer,which affects the potential response and stability of the electrode.Perfluorooctanoic acid is a low surface energy material,and doping it in polyaniline can reduce surface energy of the composite and improve surface roughness.In this work,five ammonium ion selective electrodes were prepared by doping polyaniline with different concentrations of perfluorooctanoic acid as a solid contact layer,which made the solid contact layer of electrode had hydrophobic properties,thereby improving stability of the ammonium ion selective electrode.The stability of the ion-selective electrode was evaluated by potential drift experiment,and the optimal doping concentration of perfluorooctanoic acid in the sediment solution was determined to be 5 mmol/L.The experiment results showed that the solid contact layer had a water contact angle of 132o under the doping concentration,the potential drift rate was 41.66 μV/h,and potential drift rate in the aqueous layer test was 1.31 mV/h,which were all better than those of the unmodified electrode.The standard deviation of the electrode potential was 1.42 mV,which was obviously superior to that of the unmodified electrode.The characteristics of high stability of the electrode made it suitable for long-term monitoring of ammonia nitrogen content in water samples.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

ObjectiveTo understand the incidence and mortality trends of acute cardiovascular and cerebrovascular events in Yangpu District of Shanghai from 2009 to 2022, and provide a basis for the prevention and control of cardiovascular and cerebrovascular events. MethodsData were obtained from the Shanghai Acute Cardiovascular and Cerebrovascular Events Surveillance Platform. Data on the incidence and mortality of cardiovascular and cerebrovascular events in the population (age group, gender) from 2009 to 2022 were collected, and the Joinpoint Regression Program version 4.9 was used to calculate the average annual percent change (AAPC) in the incidence and mortality rates of acute cardiovascular and cerebrovascular events. ResultsFrom 2009 to 2022, the crude incidence and standardized incidence rate of acute cardiovascular and cerebrovascular events in Yangpu District showed no significant changes (AAPC=1.41%, P=0.569; AAPC=-1.03%, P=0.675), the crude mortality rate of acute cardiovascular and cerebrovascular events in Yangpu District did not change significantly (AAPC=-3.04%, P=0.213), while the standardized mortality rate showed a decreasing trend (AAPC=-6.23% P=0.014). From 2009 to 2022, the crude incidence rates and age-standardized incidence rates for both males and females in Yangpu District showed no significant changes. The crude mortality trends for both genders were not significant, while the age-standardized mortality rates showed a decline (AAPC=-5.33%, P=0.029; AAPC=-7.50%, P=0.006). The incidence rate and age-standardized incidence rate were higher in males than in females. The crude incidence rates in the 30‒, 40‒, and 45‒year-old age groups increased annually (AAPC=9.13%、7.11%、4.67%, all P=0.001), and the crude mortality ratse in the 60‒, 65‒, 70‒, 75‒, 80‒, and 85‒year-old age groups declined annually (AAPC=-4.24%, P=0.044; AAPC=-5.41%, P=0.028; AAPC=-6.73%, P=0.004; AAPC=-7.46%, P=0.002; AAPC=-8.24%, P=0.002; AAPC=-6.16%, P=0.035). ConclusionFrom 2009 to 2022, the crude incidence, standardized incidence rate and crude mortality rate of cardiovascular and cerebrovascular events in Yangpu District tended to be stable, and the standardized mortality rate showed a downward trend. Men, middle-aged and young people were the key groups in the prevention and treatment of cardiovascular and cerebrovascular diseases, and it should be continued to improve the ability of medical emergency and increase the integration of medical and prevention.

BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.