OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-perf...OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.展开更多
Liver transplantation(LT)has made significant progress in the treatment of end stage liver disease(ESLD).However,many patients still die from disease progression while awaiting transplantation.As the number of patient...Liver transplantation(LT)has made significant progress in the treatment of end stage liver disease(ESLD).However,many patients still die from disease progression while awaiting transplantation.As the number of patients on LT waiting lists is increasing,and the organ shortage crisis is obvious,various efforts have been made to increase the pool of available liver grafts[1].In addition to living donor liver transplantation(LDLT),improving the utilization rate of extended criteria donor(ECD)livers is an important way.However,under traditional cold storage,ECD livers are usually associated with a higher risk of ischemic biliary disease,early allograft dysfunction(EAD)or even primary nonfunction(PNF).The frequently described definition in the literature for ECD grafts generally includes elderly,steatotic,long cold ischemia time(CIT),grafts obtained from donation after circulatory death(DCD),split liver grafts,donors with increased risk of infectious disease transmission and prolonged donor intensive care unit stay[2].展开更多
BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are rare malignancies frequently associated with liver metastases(LM).The benefit of primary tumor resection(PTR)in patients with unresectable LM remains controversial...BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are rare malignancies frequently associated with liver metastases(LM).The benefit of primary tumor resection(PTR)in patients with unresectable LM remains controversial.This study evaluates the impact of PTR on overall survival(OS)and tumor grading by integrating evidence from a systematic review,meta-analysis,and Surveillance,Epidemiology,and End Results(SEER)database analysis.AIM To evaluate the survival benefits of PTR in patients with PNETs and LM.METHODS This study was conducted in accordance with the PRISMA guidelines.A systematic literature search and meta-analysis were performed using five databases:PubMed,Web of Science,EMBASE,Cochrane Library,and CNKI,with records included up to February 2025.A total of 16 studies(n=8761;including 1 prospective and 15 retrospective studies)were included.A random-effects model was applied to pool hazard ratios for OS and odds ratios for tumor grading,with heterogeneity assessed by the I2 statistic.Risk of bias was evaluated using the ROBINS-I tool.In addition,an independent analysis based on the SEER database(n=791)was conducted using Kaplan-Meier survival curves and log-rank tests.RESULTS Meta-analysis results revealed that PTR significantly improved OS in patients showed that neither study design(prospective vs.retrospective)nor sample size(<400 vs≥400)significantly influenced the survival benefit.In terms of tumor grading,no statistically significant difference was observed between the surgical and non-surgical groups(odds ratio=1.60,95%confidence interval:0.70-3.63,P=0.26).Independent analysis of the SEER database(n=791)further confirmed the survival advantage of PTR across different tumor differentiation levels,with significant differences in OS between surgical and non-surgical groups(P<0.05).CONCLUSION PTR significantly improves OS in PNET patients with LM.However,its effect on tumor grading remains unclear,warranting further prospective studies to refine surgical strategies for this population.展开更多
Background:The benefit of adjuvant chemotherapy for stage I ovarian endometrioid carcinoma(OEC)remains controversial.Hence,the study sought to explore its value in stage I OEC patients.Methods:Stage I OEC patients(198...Background:The benefit of adjuvant chemotherapy for stage I ovarian endometrioid carcinoma(OEC)remains controversial.Hence,the study sought to explore its value in stage I OEC patients.Methods:Stage I OEC patients(1988–2018)were identified from the Surveillance,Epidemiology,and End Results(SEER)database.Multivariate Cox analysis was used to control confounders.Logistic regression was used to explore factors associated with adjuvant chemotherapy.Cox regression analysis and Kaplan-Meier curves were used to assess the survival benefits.Single-center clinical data and meta-analysis following PRISMA guidelines provided external validation.Result:Adjuvant chemotherapy correlated with improved survival(Hazard Ratio(HR):0.860,p=0.011),as did lymphadenectomy(HR:0.842,p<0.001).Higher age,pathological stage,and tumor grade negatively affected survival.Chemotherapy administration associated with higher pathological stage(IB:Odds Ratio(OR)1.565,p<0.001;IC:OR 4.091,p<0.001),higher grade(G2:OR 2.336,p<0.001;G3:OR 4.563,p<0.001),and lymphadenectomy(OR 1.148,p=0.040).Stratification analysis showed adjuvant chemotherapy failed to improve prognosis in stage IA/IB patients regardless of grade or lymphadenectomy.For stage IC patients,chemotherapy benefited grade 1-2 or grade 3 patients without lymphadenectomy,and grade 3 patients with lymphadenectomy.Meta-analysis revealed reduced recurrence in stage IC patients(OR=0.50,p=0.035).Conclusion:Adjuvant chemotherapy confers survival benefits for stage IC patients,particularly those without lymphadenectomy.展开更多
The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause o...The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality.The cardiovascular diseases that accompany diabetes include angina,myocardial infarction,stroke,peripheral artery disease,and congestive heart failure.Among the various risk factors generated secondary to hyperglycemic situations,advanced glycation end products(AGEs)are one of the important targets for future diagnosis and prevention of diabetes.In the last decade,AGEs have drawn a lot of attention due to their involvement in diabetic pathophysiology.AGEs can be derived exogenously and endogenously through various pathways.These are a nonhomogeneous,chemically diverse group of compounds formed nonenzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein,lipids,and nucleic acid.AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways.At the cellular level,they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation,inflammation,cellular proliferation,and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics.AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins;altering their structure,stability,and functions.Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities.In the present review,we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications.Furthermore,this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.展开更多
Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, like all NETs. However, the incidence of GI-NETS has been increasing in recent years. Gastric NETs (G-NETs) and duodenal NETs (D-NETs) are the commo...Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, like all NETs. However, the incidence of GI-NETS has been increasing in recent years. Gastric NETs (G-NETs) and duodenal NETs (D-NETs) are the common types of upper GI-NETs based on tumor location. G-NETs are classified into three distinct subgroups: type I, II, and III. Type I G-NETs, which are the most common subtype (70%-80% of all G-NETs), are associated with chronic atrophic gastritis, including autoimmune gastritis and Helicobacter pylori associated atrophic gastritis. Type II G-NETs (5%-6%) are associated with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome (MEN1-ZES). Both type I and II G-NETs are related to hypergastrinemia, are small in size, occur in multiple numbers, and are generally benign. In contrast, type III G-NETs (10%-15%) are not associated with hypergastrinemia, are large-sized single tumors, and are usually malignant. Therefore, surgical resection and chemotherapy are generally necessary for type III G-NETs, while endoscopic resection and follow-up, which are acceptable for the treatment of most type I and II G-NETs, are only acceptable for small and well differentiated type III G-NETs. D-NETs include gastrinomas (50%-60%), somatostatin-producing tumors (15%), nonfunctional serotonin-containing tumors (20%), poorly differentiated neuroendocrine carcinomas (< 3%), and gangliocytic paragangliomas (< 2%). Most D-NETs are located in the first or second part of the duodenum, with 20% occurring in the periampullary region. Therapy for D-NETs is based on tumor size, location, histological grade, stage, and tumor type. While endoscopic resection may be considered for small nonfunctional D-NETs (G1) located in the higher papilla region, surgical resection is necessary for most other D-NETs. However, there is no consensus regarding the ideal treatment of D-NETs.展开更多
BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal tract.Currently,only a few cases have been reported,resulting in limited information on survival.AIM To develop a dynamic nomogram ...BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal tract.Currently,only a few cases have been reported,resulting in limited information on survival.AIM To develop a dynamic nomogram using internal and external validation to predict survival in patients with ampullary adenocarcinoma.METHODS Data were sourced from the surveillance,epidemiology,and end results stat database.The patients in the database were randomized in a 7:3 ratio into training and validation groups.Using Cox regression univariate and multivariate analyses in the training group,we identified independent risk factors for overall survival and cancer-specific survival to develop the nomogram.The nomogram was validated with a cohort of patients from the First Affiliated Hospital of the Army Medical University.RESULTS For overall and cancer-specific survival,12(sex,age,race,lymph node ratio,tumor size,chemotherapy,surgical modality,T stage,tumor differentiation,brain metastasis,lung metastasis,and extension)and 6(age;surveillance,epidemiology,and end results stage;lymph node ratio;chemotherapy;surgical modality;and tumor differentiation)independent risk factors,respectively,were incorporated into the nomogram.The area under the curve values at 1,3,and 5 years,respectively,were 0.807,0.842,and 0.826 for overall survival and 0.816,0.835,and 0.841 for cancer-specific survival.The internal and external validation cohorts indicated good consistency of the nomogram.CONCLUSION The dynamic nomogram offers robust predictive efficacy for the overall and cancer-specific survival of ampullary adenocarcinoma.展开更多
Acceptor-donor-acceptor(A-D-A)type molecules,of which the novel non-fused azacyclic end-group pyrazoli-nones were modified with chlorine substitution on the phenyl ring,were synthesized.The non-fused azacyclic end-gro...Acceptor-donor-acceptor(A-D-A)type molecules,of which the novel non-fused azacyclic end-group pyrazoli-nones were modified with chlorine substitution on the phenyl ring,were synthesized.The non-fused azacyclic end-group py-razolinones have the advantages of simple synthesis steps,low cost and environmental friendliness,compared to the classical end-group dicyanomethyleneindianone.The properties of the synthesized A-D-A type molecules with non-fused azacyclic end groups were characterized by theoretical calculation,UV-vis absorption,cyclic voltammetry,X-ray diffraction and space charge limited current.It is shown that the strong UV-vis absorptions of the synthesized A-D-A type molecules are located in the wavelength range of 500~700 nm,with a moderate band gap of nearly 1.7 eV.At the same time,the influence of end-group chlorination on the properties of A-D-A type molecules was compared and explored.It is proven that this kind of A-D-A type molecule with non-fused azacyclic end groups has the potential to be applied as interfacial modified layer of the active layer in perovskite solar cell devices.展开更多
BACKGROUND Lung ultrasonography is being increasingly used in mechanically ventilated patients to evaluate the lung aeration during incremental positive end expiratory pressure(PEEP)adjustments and to evaluate the wea...BACKGROUND Lung ultrasonography is being increasingly used in mechanically ventilated patients to evaluate the lung aeration during incremental positive end expiratory pressure(PEEP)adjustments and to evaluate the weaning process from mechanical ventilation.The effects of PEEP may vary across different lung pathologies and may not consistently correlate with changes in lung aeration as assessed by lung ultrasound scores(LUSs).AIM To assess the role of lung ultrasonography in evaluating lung aeration during the application of PEEP in mechanically ventilated patients with various lung pathologies.METHODS An observational study was conducted over 18 months in a tertiary care hospital.Patients of both genders,aged between 18-75 years,who had been admitted to the intensive care unit,and required mechanical ventilation,were studied.A standard ventilatory strategy was used and incremental levels of PEEP[5,10,and 15 cm water(H_(2)O)]were applied.Baseline characteristics,including oxygen saturation(SpO2),LUS,mean arterial pressure(MAP),heart rate(HR),and their changes with incremental PEEP levels,were recorded and analyzed.RESULTS In this study,45.9%of patients required a PEEP of 5 cm H_(2)O to achieve the endpoint of lung aeration(LUS of 0).In addition,86.5% and 13.5% of patients reached the endpoint of lung aeration at PEEP levels of 10 and 15 cm H_(2)O,respectively.The proportion of patients with higher lung scores decreased significantly with increasing PEEP levels(P<0.001 for 5 and 10 cm H_(2)O and P=0.032 for 15 cm H_(2)O).SpO2 increased significantly with higher PEEP levels(P<0.001),confirming the effectiveness of PEEP in improving oxygenation.The results also revealed a significant increase in HR and a decrease in MAP following the application of higher PEEP levels.CONCLUSION Increasing PEEP levels in mechanically ventilated patients improves lung aeration,which can be effectively assessed using bedside lung ultrasonography.展开更多
Although it is known that the accumulation of methylglyoxal(MGO)and advanced glycosylation end products(AGEs)results in oxidative injury,the comparison between caffeic acid(CA)and chlorogenic acid(CGA)against oxidativ...Although it is known that the accumulation of methylglyoxal(MGO)and advanced glycosylation end products(AGEs)results in oxidative injury,the comparison between caffeic acid(CA)and chlorogenic acid(CGA)against oxidative damage remains unclear.Therefore,this study was conducted to compare the effects of CA and CGA using PC12 cells and Caenorhabditis elegans.The antioxidant regulatory targets for CA and CGA were primarily detected in the NRF2 pathway as predicted by network pharmacology.First,CA exerted higher effects than CGA in increasing cell viability and mitochondrial membrane potential,reducing ROS production and apoptosis,and promoting the expression of NRF2 translocation and downstream genes,which were consistent with the results of molecular docking,molecular dynamics,and covariance matrix simulations.Second,treatment with ML385(Nrf2 inhibitor)eliminated the anti-cytotoxic effect and ROS accumulation reduction effect of CA and CGA.Third,CA exhibited stronger capacities in extending lifespan,inhibiting ROS production,and increasing SKN-1 proportion than CGA in C.elegans.Multi-spectroscopy analysis also revealed a stronger inhibitory effect of CA on the formation of AGEs than that of CGA,which might be related to the alteration of the proteinα-helix.Therefore,considering the higher antioxidant effects of CA,it can be used as a promising antioxidant natural drug resource.展开更多
Chromosomal DNA double-strand breaks(DSBs)are often generated in the genome of all living organisms.To combat DNA damage,organisms have evolved several DSB repair mechanisms,with nonhomologous end-joining(NHEJ)and hom...Chromosomal DNA double-strand breaks(DSBs)are often generated in the genome of all living organisms.To combat DNA damage,organisms have evolved several DSB repair mechanisms,with nonhomologous end-joining(NHEJ)and homologous recombination(HR)being the two most prominent.Although two major pathways have been extensively studied in Arabidopsis,rice and other mammals,the exact functions and differences between the two DSB repair pathways in maize still remain less well understood.Here,we characterized mre11a and rad50,mutants of HR pathway patterns,which showed drastic degradation of the typically persistent embryo and endosperm during kernel development.Loss of MRE11 or RAD50 function led to chromosomal fragments and chromosomal bridges in anaphase.While we also reported that the NHEJ pathway patterns,KU70 and KU80 are associated with developmental growth and genome stability.ku70 and ku80 both displayed an obvious dwarf phenotype.Cytological analysis of the mutants revealed extensive chromosome fragmentation in metaphase and subsequent stages.Loss of KU70/80 function upregulated the expression of genes involved in cell cycle progression and nuclear division.These results provide insights into how NHEJ and HR are mechanistically executed during different plant developmental periods and highlight a competitive and complementary relationship between the NHEJ and HR pathways for DNA double-strand break repair in maize.展开更多
BACKGROUND Esophageal cancer is a significant global health concern,characterized by high mortality rates and diverse histological types,primarily adenocarcinoma and squamous cell carcinoma.AIM To analyze trends in es...BACKGROUND Esophageal cancer is a significant global health concern,characterized by high mortality rates and diverse histological types,primarily adenocarcinoma and squamous cell carcinoma.AIM To analyze trends in esophageal cancer using Surveillance,Epidemiology,and End Results(SEER)data,focusing on patient characteristics,stage at diagnosis,treatment modalities,and survival outcomes,to provide insights that may guide clinical practice and public health initiatives.METHODS Age-adjusted incidence and mortality rates for esophageal cancer,2004-2021,were obtained from SEER rate sessions using SEER*Stat version 8.4.4.Average percent changes(APC)over time in age-adjusted incidence and mortality rates relative to gender,race/ethnicity,and stage at diagnosis were assessed using Joinpoint’s loglinear regression.Finally,Poisson regression was used to ascertain incidence and mortality rate ratios to ascertain associations between age,gender,race/ethnicity,and staging with incidence and mortality rates.All analyses were further stratified by gender to assess interactions between gender and the other demographic and clinical characteristics.RESULTS Overall,the data reveals significant trends in both the incidence and mortality rates of esophageal cancer,with notable variations across gender,race,and stage at diagnosis.Age-adjusted incidence and mortality rates were higher in males compared to females(incidence:4.1 per 100000 vs 0.9 per 100000,mortality:3.4 per 100000 vs 0.7 per 100000),P<0.001.Furthermore,the APC among males decreased more significantly over time[APC(95%CI):-1.14(-1.52 to-0.78);P<0.001].Both non-Hispanic(NH)Blacks and NH Whites showed significant decreases in cancer incidence,with NH Blacks observing a 3.27%decline and NH Whites a 0.51%decline.Patients with distant staging had a 5%APC increase in mortality rates over time(P=0.003).Additionally,mortality rates increased with age,and all minority groups showed declines in incidence and mortality compared to NH Whites.Cancer diagnosed at a distant stage had a mortality rate 4.16 times higher than in situ cases.CONCLUSION The analysis reveals clear disparities in both the incidence and mortality of esophageal cancer,with males,particularly NH Whites,experiencing significantly higher rates than females.Despite a general decline in incidence rates over time,the upward trend in mortality for certain subgroups warrants further investigation into potential contributing factors such as healthcare access,treatment efficacy,and underlying socio-economic disparities.展开更多
To improve the accuracy of thermal response estimation and overcome the limitations of the linear regression model and Artificial Neural Network(ANN)model,this study introduces a deep learning estimation method specif...To improve the accuracy of thermal response estimation and overcome the limitations of the linear regression model and Artificial Neural Network(ANN)model,this study introduces a deep learning estimation method specifically based on the Long Short-Term Memory(LSTM)network,to predict temperature-induced girder end displacements of the Dasha Waterway Bridge,a suspension bridge in China.First,to enhance data quality and select target sensors,preprocessing based on the sigma rule and nearest neighbor interpolation is applied to the raw data.Furthermore,to eliminate the high-frequency components from the displacement signal,the wavelet transform is conducted.Subsequently,the linear regression model and ANN model are established,whose results do not meet the requirements and fail to address the time lag effect between temperature and displacements.The study proceeds to develop the LSTM network model and determine the optimal parameters through hyperparameter sensitivity analysis.Finally,the results of the LSTM network model are discussed by a comparative analysis against the linear regression model and ANN model,which indicates a higher accuracy in predicting temperatureinduced girder end displacements and the ability to mitigate the time-lag effect.To be more specific,in comparison between the linear regression model and LSTM network,the mean square error decreases from 6.5937 to 1.6808 and R^(2) increases from 0.683 to 0.930,which corresponds to a 74.51%decrease in MSE and a 36.14%improvement in R^(2).Compared to ANN,with an MSE of 4.6371 and an R^(2) of 0.807,LSTM shows a decrease in MSE of 63.75%and an increase in R^(2) of 13.23%,demonstrating a significant enhancement in predictive performance.展开更多
This article is a part of a larger study called The Abstract Truth of Media focused on the topic of the fictional media content opinions presented and perceived as truth.It will explore the abstract nature of truth in...This article is a part of a larger study called The Abstract Truth of Media focused on the topic of the fictional media content opinions presented and perceived as truth.It will explore the abstract nature of truth in online media and its different forms.These media truths are types of fictional stories with certain effects on the public rather than a truthful presentation of the facts.Thus,the end goal of mass media today is not to tell the truth,but to create moral communities based on common experience and beliefs.Articles,opinions,and news in media are seen as a narrative strategy that can be understood only through storytelling analysis.Here the focus is on the understanding of Truth and Untruth in online media as well as the connection of Internet media technology with the increase of disinformation online.The new media model creates hostile groups instead of generating consent for the nation-state,the new online media model within through,Pseudo-communication,manipulation,delusion,lies,propaganda,and deliberate causing of moral anger.“The end of the truth”means that the truth on the Internet is lost among the vast amount of information and the lack of regulation regarding the correctness of the published data.Instead of truth,media researchers formally talk about post-truth,fake news,and“alternative facts”.Truth on the Internet is more like“Truthiness”or a belief that a statement is true based on the intuition or understanding of individuals,regardless of evidence,logic or facts.The subject of research is the connection between every new technology in mass media and the truth of the information and the effects on the consensus in society.Since the beginning of the 21st century,misinformation on the Internet has increased with the development of online media and social networks,and it is a problem of social peace and consent in every country.展开更多
Sepsis management has significantly improved over the past decades,with intensivists playing a pivotal role in its identification and treatment.[1,2]However,resource constraints in large tertiary hospitals in China li...Sepsis management has significantly improved over the past decades,with intensivists playing a pivotal role in its identification and treatment.[1,2]However,resource constraints in large tertiary hospitals in China limit patient admissions,leading to overcrowding in the emergency departments(EDs)with critically ill patients.[3]This highlights the urgent need for enhanced risk stratification and optimized sepsis management in emergency settings.展开更多
Advanced glycation end products(AGEs),a group of complex compounds generated by nonenzymatic interactions between amino acids,proteins and reducing sugars or lipids,accumulate in vivo and activate various signaling pa...Advanced glycation end products(AGEs),a group of complex compounds generated by nonenzymatic interactions between amino acids,proteins and reducing sugars or lipids,accumulate in vivo and activate various signaling pathways closely related to the occurrence of various chronic metabolic diseases.This study aims to explore the structure-activity relationship between phenolic acids with different structure and affecting the AGEs generation,and to provide data support for AGEs control.Phenolic acids(4-hydroxybenzoic,protocatechuic,gallic,p-coumaric,caffeic,ferulic and sinapic acids)were employed to indicate the AGEs formation condition in Maillard reaction performed in the glucose-lysine model system.Three 1,2-dicarbonyl compounds were reacted with phenolic acids and then tested by liquid chromatography-mass spectrometry.The results showed that N^(ε)-carboxy-methyl-lysine(CML),N^(ε)-carboxy-ethyl-lysine(CEL),and pyrraline formation inhibited by phenolic acids varied from(8.7±2.5)%to(33.2±2.5)%,(10.5±0.8)%to(57.1±3.2)%and(1.3±0.3)%to(23.3±0.8)%,respectively.The p-coumaric acid has no inhibitory effect on CML and CEL formation.Gallic acid shows the best inhibitory effect on CML formation due to its strong antioxidant activity.Sinapic acid showed the best glyoxal(GO)trapping rate and thus had the stronger inhibitory effect on CML formation.Ferulic acid can react with mono-,di-,and tri-methylglyoxal(MGO)to form adduct products,showing the best MGO scavenging rate and a good inhibitory effect on CEL formation.The main role of phenolic acid is an antioxidant agent to inhibit pyrraline formation.The glucose itself or ammonia-induced degradation and Amadori rearrangement products oxidation were lowered by protocatechuic,gallic and caffeic acids due to their antioxidant activities to form AGEs,while AGEs inhibited by ferulic and sinapic acids were mainly dependent on their trapping ability on 1,2-dicarbonyl compounds.展开更多
基金the Guangdong Provincial Basic and Applied Basic Research Project:Mechanistic Study on the Regulation of Inflammatory Microenvironment and Improvement of Ulcerative Colitis by Lingnan Traditional Medicine Ficus Pandurata Hance through Wilms'Tumor 1-associating Protein-Mediated RNA Methyltransferase Promoting Toll Like Receptor 4 m6A Modification(2023A1515011699)the Zhongshan Medical Research Project:Mechanistic Study on the Action of Xiahuo Pingwei San in the Treatment of Ulcerative Colitis(2022A020446)。
文摘OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.
文摘Liver transplantation(LT)has made significant progress in the treatment of end stage liver disease(ESLD).However,many patients still die from disease progression while awaiting transplantation.As the number of patients on LT waiting lists is increasing,and the organ shortage crisis is obvious,various efforts have been made to increase the pool of available liver grafts[1].In addition to living donor liver transplantation(LDLT),improving the utilization rate of extended criteria donor(ECD)livers is an important way.However,under traditional cold storage,ECD livers are usually associated with a higher risk of ischemic biliary disease,early allograft dysfunction(EAD)or even primary nonfunction(PNF).The frequently described definition in the literature for ECD grafts generally includes elderly,steatotic,long cold ischemia time(CIT),grafts obtained from donation after circulatory death(DCD),split liver grafts,donors with increased risk of infectious disease transmission and prolonged donor intensive care unit stay[2].
文摘BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are rare malignancies frequently associated with liver metastases(LM).The benefit of primary tumor resection(PTR)in patients with unresectable LM remains controversial.This study evaluates the impact of PTR on overall survival(OS)and tumor grading by integrating evidence from a systematic review,meta-analysis,and Surveillance,Epidemiology,and End Results(SEER)database analysis.AIM To evaluate the survival benefits of PTR in patients with PNETs and LM.METHODS This study was conducted in accordance with the PRISMA guidelines.A systematic literature search and meta-analysis were performed using five databases:PubMed,Web of Science,EMBASE,Cochrane Library,and CNKI,with records included up to February 2025.A total of 16 studies(n=8761;including 1 prospective and 15 retrospective studies)were included.A random-effects model was applied to pool hazard ratios for OS and odds ratios for tumor grading,with heterogeneity assessed by the I2 statistic.Risk of bias was evaluated using the ROBINS-I tool.In addition,an independent analysis based on the SEER database(n=791)was conducted using Kaplan-Meier survival curves and log-rank tests.RESULTS Meta-analysis results revealed that PTR significantly improved OS in patients showed that neither study design(prospective vs.retrospective)nor sample size(<400 vs≥400)significantly influenced the survival benefit.In terms of tumor grading,no statistically significant difference was observed between the surgical and non-surgical groups(odds ratio=1.60,95%confidence interval:0.70-3.63,P=0.26).Independent analysis of the SEER database(n=791)further confirmed the survival advantage of PTR across different tumor differentiation levels,with significant differences in OS between surgical and non-surgical groups(P<0.05).CONCLUSION PTR significantly improves OS in PNET patients with LM.However,its effect on tumor grading remains unclear,warranting further prospective studies to refine surgical strategies for this population.
基金supported by the scientific research project of Jiangsu Province’s“333 Project”(BRA2019097)Jiangsu Provincial Key Medical Discipline of the 14th Five-Year Plan(ZDXK202210)Jiangsu Province Medicine Science and Technology Development Project(No.ZD202014).
文摘Background:The benefit of adjuvant chemotherapy for stage I ovarian endometrioid carcinoma(OEC)remains controversial.Hence,the study sought to explore its value in stage I OEC patients.Methods:Stage I OEC patients(1988–2018)were identified from the Surveillance,Epidemiology,and End Results(SEER)database.Multivariate Cox analysis was used to control confounders.Logistic regression was used to explore factors associated with adjuvant chemotherapy.Cox regression analysis and Kaplan-Meier curves were used to assess the survival benefits.Single-center clinical data and meta-analysis following PRISMA guidelines provided external validation.Result:Adjuvant chemotherapy correlated with improved survival(Hazard Ratio(HR):0.860,p=0.011),as did lymphadenectomy(HR:0.842,p<0.001).Higher age,pathological stage,and tumor grade negatively affected survival.Chemotherapy administration associated with higher pathological stage(IB:Odds Ratio(OR)1.565,p<0.001;IC:OR 4.091,p<0.001),higher grade(G2:OR 2.336,p<0.001;G3:OR 4.563,p<0.001),and lymphadenectomy(OR 1.148,p=0.040).Stratification analysis showed adjuvant chemotherapy failed to improve prognosis in stage IA/IB patients regardless of grade or lymphadenectomy.For stage IC patients,chemotherapy benefited grade 1-2 or grade 3 patients without lymphadenectomy,and grade 3 patients with lymphadenectomy.Meta-analysis revealed reduced recurrence in stage IC patients(OR=0.50,p=0.035).Conclusion:Adjuvant chemotherapy confers survival benefits for stage IC patients,particularly those without lymphadenectomy.
文摘The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality.The cardiovascular diseases that accompany diabetes include angina,myocardial infarction,stroke,peripheral artery disease,and congestive heart failure.Among the various risk factors generated secondary to hyperglycemic situations,advanced glycation end products(AGEs)are one of the important targets for future diagnosis and prevention of diabetes.In the last decade,AGEs have drawn a lot of attention due to their involvement in diabetic pathophysiology.AGEs can be derived exogenously and endogenously through various pathways.These are a nonhomogeneous,chemically diverse group of compounds formed nonenzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein,lipids,and nucleic acid.AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways.At the cellular level,they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation,inflammation,cellular proliferation,and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics.AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins;altering their structure,stability,and functions.Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities.In the present review,we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications.Furthermore,this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.
文摘Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, like all NETs. However, the incidence of GI-NETS has been increasing in recent years. Gastric NETs (G-NETs) and duodenal NETs (D-NETs) are the common types of upper GI-NETs based on tumor location. G-NETs are classified into three distinct subgroups: type I, II, and III. Type I G-NETs, which are the most common subtype (70%-80% of all G-NETs), are associated with chronic atrophic gastritis, including autoimmune gastritis and Helicobacter pylori associated atrophic gastritis. Type II G-NETs (5%-6%) are associated with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome (MEN1-ZES). Both type I and II G-NETs are related to hypergastrinemia, are small in size, occur in multiple numbers, and are generally benign. In contrast, type III G-NETs (10%-15%) are not associated with hypergastrinemia, are large-sized single tumors, and are usually malignant. Therefore, surgical resection and chemotherapy are generally necessary for type III G-NETs, while endoscopic resection and follow-up, which are acceptable for the treatment of most type I and II G-NETs, are only acceptable for small and well differentiated type III G-NETs. D-NETs include gastrinomas (50%-60%), somatostatin-producing tumors (15%), nonfunctional serotonin-containing tumors (20%), poorly differentiated neuroendocrine carcinomas (< 3%), and gangliocytic paragangliomas (< 2%). Most D-NETs are located in the first or second part of the duodenum, with 20% occurring in the periampullary region. Therapy for D-NETs is based on tumor size, location, histological grade, stage, and tumor type. While endoscopic resection may be considered for small nonfunctional D-NETs (G1) located in the higher papilla region, surgical resection is necessary for most other D-NETs. However, there is no consensus regarding the ideal treatment of D-NETs.
基金Supported by the Appropriate Technology Promotion Program in Chongqing,No.2023jstg005.
文摘BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal tract.Currently,only a few cases have been reported,resulting in limited information on survival.AIM To develop a dynamic nomogram using internal and external validation to predict survival in patients with ampullary adenocarcinoma.METHODS Data were sourced from the surveillance,epidemiology,and end results stat database.The patients in the database were randomized in a 7:3 ratio into training and validation groups.Using Cox regression univariate and multivariate analyses in the training group,we identified independent risk factors for overall survival and cancer-specific survival to develop the nomogram.The nomogram was validated with a cohort of patients from the First Affiliated Hospital of the Army Medical University.RESULTS For overall and cancer-specific survival,12(sex,age,race,lymph node ratio,tumor size,chemotherapy,surgical modality,T stage,tumor differentiation,brain metastasis,lung metastasis,and extension)and 6(age;surveillance,epidemiology,and end results stage;lymph node ratio;chemotherapy;surgical modality;and tumor differentiation)independent risk factors,respectively,were incorporated into the nomogram.The area under the curve values at 1,3,and 5 years,respectively,were 0.807,0.842,and 0.826 for overall survival and 0.816,0.835,and 0.841 for cancer-specific survival.The internal and external validation cohorts indicated good consistency of the nomogram.CONCLUSION The dynamic nomogram offers robust predictive efficacy for the overall and cancer-specific survival of ampullary adenocarcinoma.
文摘Acceptor-donor-acceptor(A-D-A)type molecules,of which the novel non-fused azacyclic end-group pyrazoli-nones were modified with chlorine substitution on the phenyl ring,were synthesized.The non-fused azacyclic end-group py-razolinones have the advantages of simple synthesis steps,low cost and environmental friendliness,compared to the classical end-group dicyanomethyleneindianone.The properties of the synthesized A-D-A type molecules with non-fused azacyclic end groups were characterized by theoretical calculation,UV-vis absorption,cyclic voltammetry,X-ray diffraction and space charge limited current.It is shown that the strong UV-vis absorptions of the synthesized A-D-A type molecules are located in the wavelength range of 500~700 nm,with a moderate band gap of nearly 1.7 eV.At the same time,the influence of end-group chlorination on the properties of A-D-A type molecules was compared and explored.It is proven that this kind of A-D-A type molecule with non-fused azacyclic end groups has the potential to be applied as interfacial modified layer of the active layer in perovskite solar cell devices.
文摘BACKGROUND Lung ultrasonography is being increasingly used in mechanically ventilated patients to evaluate the lung aeration during incremental positive end expiratory pressure(PEEP)adjustments and to evaluate the weaning process from mechanical ventilation.The effects of PEEP may vary across different lung pathologies and may not consistently correlate with changes in lung aeration as assessed by lung ultrasound scores(LUSs).AIM To assess the role of lung ultrasonography in evaluating lung aeration during the application of PEEP in mechanically ventilated patients with various lung pathologies.METHODS An observational study was conducted over 18 months in a tertiary care hospital.Patients of both genders,aged between 18-75 years,who had been admitted to the intensive care unit,and required mechanical ventilation,were studied.A standard ventilatory strategy was used and incremental levels of PEEP[5,10,and 15 cm water(H_(2)O)]were applied.Baseline characteristics,including oxygen saturation(SpO2),LUS,mean arterial pressure(MAP),heart rate(HR),and their changes with incremental PEEP levels,were recorded and analyzed.RESULTS In this study,45.9%of patients required a PEEP of 5 cm H_(2)O to achieve the endpoint of lung aeration(LUS of 0).In addition,86.5% and 13.5% of patients reached the endpoint of lung aeration at PEEP levels of 10 and 15 cm H_(2)O,respectively.The proportion of patients with higher lung scores decreased significantly with increasing PEEP levels(P<0.001 for 5 and 10 cm H_(2)O and P=0.032 for 15 cm H_(2)O).SpO2 increased significantly with higher PEEP levels(P<0.001),confirming the effectiveness of PEEP in improving oxygenation.The results also revealed a significant increase in HR and a decrease in MAP following the application of higher PEEP levels.CONCLUSION Increasing PEEP levels in mechanically ventilated patients improves lung aeration,which can be effectively assessed using bedside lung ultrasonography.
基金supported by the Open Project of State Key Laboratory of Food Nutrition and Safety,Tianjin University of Science&Technology(SKLFNS-KF-202201)Tianjin Food Processing Control and Safety Engineering Technology Center(GCZX202303)。
文摘Although it is known that the accumulation of methylglyoxal(MGO)and advanced glycosylation end products(AGEs)results in oxidative injury,the comparison between caffeic acid(CA)and chlorogenic acid(CGA)against oxidative damage remains unclear.Therefore,this study was conducted to compare the effects of CA and CGA using PC12 cells and Caenorhabditis elegans.The antioxidant regulatory targets for CA and CGA were primarily detected in the NRF2 pathway as predicted by network pharmacology.First,CA exerted higher effects than CGA in increasing cell viability and mitochondrial membrane potential,reducing ROS production and apoptosis,and promoting the expression of NRF2 translocation and downstream genes,which were consistent with the results of molecular docking,molecular dynamics,and covariance matrix simulations.Second,treatment with ML385(Nrf2 inhibitor)eliminated the anti-cytotoxic effect and ROS accumulation reduction effect of CA and CGA.Third,CA exhibited stronger capacities in extending lifespan,inhibiting ROS production,and increasing SKN-1 proportion than CGA in C.elegans.Multi-spectroscopy analysis also revealed a stronger inhibitory effect of CA on the formation of AGEs than that of CGA,which might be related to the alteration of the proteinα-helix.Therefore,considering the higher antioxidant effects of CA,it can be used as a promising antioxidant natural drug resource.
基金supported by the National Natural Science Foundation of China(32372116)to Yan He.
文摘Chromosomal DNA double-strand breaks(DSBs)are often generated in the genome of all living organisms.To combat DNA damage,organisms have evolved several DSB repair mechanisms,with nonhomologous end-joining(NHEJ)and homologous recombination(HR)being the two most prominent.Although two major pathways have been extensively studied in Arabidopsis,rice and other mammals,the exact functions and differences between the two DSB repair pathways in maize still remain less well understood.Here,we characterized mre11a and rad50,mutants of HR pathway patterns,which showed drastic degradation of the typically persistent embryo and endosperm during kernel development.Loss of MRE11 or RAD50 function led to chromosomal fragments and chromosomal bridges in anaphase.While we also reported that the NHEJ pathway patterns,KU70 and KU80 are associated with developmental growth and genome stability.ku70 and ku80 both displayed an obvious dwarf phenotype.Cytological analysis of the mutants revealed extensive chromosome fragmentation in metaphase and subsequent stages.Loss of KU70/80 function upregulated the expression of genes involved in cell cycle progression and nuclear division.These results provide insights into how NHEJ and HR are mechanistically executed during different plant developmental periods and highlight a competitive and complementary relationship between the NHEJ and HR pathways for DNA double-strand break repair in maize.
文摘BACKGROUND Esophageal cancer is a significant global health concern,characterized by high mortality rates and diverse histological types,primarily adenocarcinoma and squamous cell carcinoma.AIM To analyze trends in esophageal cancer using Surveillance,Epidemiology,and End Results(SEER)data,focusing on patient characteristics,stage at diagnosis,treatment modalities,and survival outcomes,to provide insights that may guide clinical practice and public health initiatives.METHODS Age-adjusted incidence and mortality rates for esophageal cancer,2004-2021,were obtained from SEER rate sessions using SEER*Stat version 8.4.4.Average percent changes(APC)over time in age-adjusted incidence and mortality rates relative to gender,race/ethnicity,and stage at diagnosis were assessed using Joinpoint’s loglinear regression.Finally,Poisson regression was used to ascertain incidence and mortality rate ratios to ascertain associations between age,gender,race/ethnicity,and staging with incidence and mortality rates.All analyses were further stratified by gender to assess interactions between gender and the other demographic and clinical characteristics.RESULTS Overall,the data reveals significant trends in both the incidence and mortality rates of esophageal cancer,with notable variations across gender,race,and stage at diagnosis.Age-adjusted incidence and mortality rates were higher in males compared to females(incidence:4.1 per 100000 vs 0.9 per 100000,mortality:3.4 per 100000 vs 0.7 per 100000),P<0.001.Furthermore,the APC among males decreased more significantly over time[APC(95%CI):-1.14(-1.52 to-0.78);P<0.001].Both non-Hispanic(NH)Blacks and NH Whites showed significant decreases in cancer incidence,with NH Blacks observing a 3.27%decline and NH Whites a 0.51%decline.Patients with distant staging had a 5%APC increase in mortality rates over time(P=0.003).Additionally,mortality rates increased with age,and all minority groups showed declines in incidence and mortality compared to NH Whites.Cancer diagnosed at a distant stage had a mortality rate 4.16 times higher than in situ cases.CONCLUSION The analysis reveals clear disparities in both the incidence and mortality of esophageal cancer,with males,particularly NH Whites,experiencing significantly higher rates than females.Despite a general decline in incidence rates over time,the upward trend in mortality for certain subgroups warrants further investigation into potential contributing factors such as healthcare access,treatment efficacy,and underlying socio-economic disparities.
基金The National Key Research and Development Program of China grant No.2022YFB3706704 received by Yuan Renthe National Natural and Science Foundation of China grant No.52308150 received by Xiang Xu.
文摘To improve the accuracy of thermal response estimation and overcome the limitations of the linear regression model and Artificial Neural Network(ANN)model,this study introduces a deep learning estimation method specifically based on the Long Short-Term Memory(LSTM)network,to predict temperature-induced girder end displacements of the Dasha Waterway Bridge,a suspension bridge in China.First,to enhance data quality and select target sensors,preprocessing based on the sigma rule and nearest neighbor interpolation is applied to the raw data.Furthermore,to eliminate the high-frequency components from the displacement signal,the wavelet transform is conducted.Subsequently,the linear regression model and ANN model are established,whose results do not meet the requirements and fail to address the time lag effect between temperature and displacements.The study proceeds to develop the LSTM network model and determine the optimal parameters through hyperparameter sensitivity analysis.Finally,the results of the LSTM network model are discussed by a comparative analysis against the linear regression model and ANN model,which indicates a higher accuracy in predicting temperatureinduced girder end displacements and the ability to mitigate the time-lag effect.To be more specific,in comparison between the linear regression model and LSTM network,the mean square error decreases from 6.5937 to 1.6808 and R^(2) increases from 0.683 to 0.930,which corresponds to a 74.51%decrease in MSE and a 36.14%improvement in R^(2).Compared to ANN,with an MSE of 4.6371 and an R^(2) of 0.807,LSTM shows a decrease in MSE of 63.75%and an increase in R^(2) of 13.23%,demonstrating a significant enhancement in predictive performance.
文摘This article is a part of a larger study called The Abstract Truth of Media focused on the topic of the fictional media content opinions presented and perceived as truth.It will explore the abstract nature of truth in online media and its different forms.These media truths are types of fictional stories with certain effects on the public rather than a truthful presentation of the facts.Thus,the end goal of mass media today is not to tell the truth,but to create moral communities based on common experience and beliefs.Articles,opinions,and news in media are seen as a narrative strategy that can be understood only through storytelling analysis.Here the focus is on the understanding of Truth and Untruth in online media as well as the connection of Internet media technology with the increase of disinformation online.The new media model creates hostile groups instead of generating consent for the nation-state,the new online media model within through,Pseudo-communication,manipulation,delusion,lies,propaganda,and deliberate causing of moral anger.“The end of the truth”means that the truth on the Internet is lost among the vast amount of information and the lack of regulation regarding the correctness of the published data.Instead of truth,media researchers formally talk about post-truth,fake news,and“alternative facts”.Truth on the Internet is more like“Truthiness”or a belief that a statement is true based on the intuition or understanding of individuals,regardless of evidence,logic or facts.The subject of research is the connection between every new technology in mass media and the truth of the information and the effects on the consensus in society.Since the beginning of the 21st century,misinformation on the Internet has increased with the development of online media and social networks,and it is a problem of social peace and consent in every country.
基金supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-062,to BD).
文摘Sepsis management has significantly improved over the past decades,with intensivists playing a pivotal role in its identification and treatment.[1,2]However,resource constraints in large tertiary hospitals in China limit patient admissions,leading to overcrowding in the emergency departments(EDs)with critically ill patients.[3]This highlights the urgent need for enhanced risk stratification and optimized sepsis management in emergency settings.
基金supported by the National Natural Science Foundation of China(32472468 and 32001817)the Fundamental Research Program of Shanxi Province(202303021221123)+1 种基金the Youth Project of the Shanxi Fundamental Research Program(202203021222032)theStart-up Funds forScientific Research atNorth University of China(304-1101285714).
文摘Advanced glycation end products(AGEs),a group of complex compounds generated by nonenzymatic interactions between amino acids,proteins and reducing sugars or lipids,accumulate in vivo and activate various signaling pathways closely related to the occurrence of various chronic metabolic diseases.This study aims to explore the structure-activity relationship between phenolic acids with different structure and affecting the AGEs generation,and to provide data support for AGEs control.Phenolic acids(4-hydroxybenzoic,protocatechuic,gallic,p-coumaric,caffeic,ferulic and sinapic acids)were employed to indicate the AGEs formation condition in Maillard reaction performed in the glucose-lysine model system.Three 1,2-dicarbonyl compounds were reacted with phenolic acids and then tested by liquid chromatography-mass spectrometry.The results showed that N^(ε)-carboxy-methyl-lysine(CML),N^(ε)-carboxy-ethyl-lysine(CEL),and pyrraline formation inhibited by phenolic acids varied from(8.7±2.5)%to(33.2±2.5)%,(10.5±0.8)%to(57.1±3.2)%and(1.3±0.3)%to(23.3±0.8)%,respectively.The p-coumaric acid has no inhibitory effect on CML and CEL formation.Gallic acid shows the best inhibitory effect on CML formation due to its strong antioxidant activity.Sinapic acid showed the best glyoxal(GO)trapping rate and thus had the stronger inhibitory effect on CML formation.Ferulic acid can react with mono-,di-,and tri-methylglyoxal(MGO)to form adduct products,showing the best MGO scavenging rate and a good inhibitory effect on CEL formation.The main role of phenolic acid is an antioxidant agent to inhibit pyrraline formation.The glucose itself or ammonia-induced degradation and Amadori rearrangement products oxidation were lowered by protocatechuic,gallic and caffeic acids due to their antioxidant activities to form AGEs,while AGEs inhibited by ferulic and sinapic acids were mainly dependent on their trapping ability on 1,2-dicarbonyl compounds.
