The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to r...The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to represent human chronic AC administrations for 13 days.Organ pathology was determined using hematoxylin-eosin staining and immunohistochemistry.Fecal and proximal intestinal content samples were collected to perform shotgun metagenomic sequencing.Serum samples were collected,and untargeted metabolomics was performed.In this study,AC administration induced proximal intestine,liver,and kidney injury.Microbiome composition remained stable after AC exposure,while several microbes presented dynamic alteration.Moreover,AC affected the abundance of the fatty acid biosynthesis rate-limiting gene acc A at day 7.AC induces 30 serum metabolites to significantly change at day 14,including several short-chain acylcarnitines.WGCNA revealed 2 sub-modules associated with the level of several short-chain acylcarnitines.In summary,AC affects the digestive tract and serum metabolism after chronic administration.AC may affect the enrichment of microbial-derived acc A gene.The abundance of serum acylcarnitines detected in the AC group may associate with its anti-heart failure effects.展开更多
BACKGROUND:Serum osmolality is a prognostic indicator in critically ill patients.This study aimed to evaluate the association between high osmolality and 28-day mortality in patients with cardiac arrest(CA)admitted to...BACKGROUND:Serum osmolality is a prognostic indicator in critically ill patients.This study aimed to evaluate the association between high osmolality and 28-day mortality in patients with cardiac arrest(CA)admitted to the intensive care unit(ICU).METHODS:Baseline data of adult patients with CA who were admitted to the ICU from 2008 to 2019 were collected from the Medical Information Mart for Intensive Care(MIMIC)-IV.Patients were divided into survivor and non-survivor groups according to the 28-day prognosis.Serum concentrations of sodium,potassium,glucose,and urea nitrogen on the fi rst day of ICU admission were used to determine serum osmolarity.The primary endpoint of this study was 28-day all-cause mortality.Propensity score matching(PSM)analysis was performed to reduce bias between the survivor and nonsurvivor groups.RESULTS:Among the 798 included CA patients,the high osmolarity on the first day of ICU admission remained significantly associated with increased 28-day mortality(62.0%vs.35.5%,P<0.001)and reduced cumulative survival(log-rank P<0.05)after PSM.Cox regression identifi ed the high osmolarity on the fi rst day of ICU admission as an independent predictor.High serum osmolarity on the fi rst day of ICU admission eff ectively predicted 1-,3-,7-,and 28-day all-cause mortality,with the strongest predictive performance for 1-day mortality both before and after PSM(all P<0.05).CONCLUSION:In this study,elevated serum osmolarity on the first day of ICU admission was independently associated with increased 28-day mortality in CA patients and could serve as a prognostic marker.展开更多
AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analy...AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.展开更多
In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflamma...In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.展开更多
BACKGROUND Low serum albumin levels are established predictors of adverse outcomes in various cardiovascular conditions.However,the role of serum albumin in mortality among elderly patients with chronic aortic regurgi...BACKGROUND Low serum albumin levels are established predictors of adverse outcomes in various cardiovascular conditions.However,the role of serum albumin in mortality among elderly patients with chronic aortic regurgitation(AR)has not been thoroughly investigated.This study aims to assess the relationship between serum albumin levels and mortality in this specific patient population.METHODS Our analysis included 873 elderly AR patients from the China Valvular Heart Disease study,with baseline serum albumin measured at enrollment.Mortality outcomes were monitored for two years post-enrollment,employing a Cox proportional hazards model with a two-piecewise Cox proportional hazards framework to investigate the nonlinear relationship between serum albumin levels and all-cause mortality.RESULTS During the 2-year follow-up period,we observed 63 all-cause deaths.The association between serum albumin levels and all-cause mortality displayed an approximating L-shaped curve,indicating a mortality threshold at 35 g/L.For serum albumin levels below 35 g/L,each 1 g/L decrease was associated with a 25%higher risk of all-cause mortality(HR=1.25,95%CI:1.07–1.45).In contrast,no significant change in mortality risk was observed when serum albumin levels were greater than or equal to 35 g/L.Moreover,when serum albumin is classified as hypoproteinemia(serum albumin<35 g/L),the higher risks of all-cause death were observed in hypoproteinemic patients(HR=2.93,95%CI:1.50–5.74).More importantly,the association between serum albumin and death was significantly stronger in overweight/obese patients(≥24 kg/m^(2)vs.<24 kg/m^(2),Pinteraction=0.006).CONCLUSIONS In elderly patients with AR,serum albumin levels showed an approximating L-shaped relationship with all-cause death,with thresholds of 35 g/L.Body mass index was significant effect modifiers of the association.These results suggest that serum albumin,as an inexpensive and readily available biochemical marker,may further improve the stratified risk of mortality in older AR patients.展开更多
BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer(GC)resection despite the substantial...BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer(GC)resection despite the substantial curative benefits provided by surgical interventions for GC.Hence,the investigation of more optimal and efficacious treatment approaches has become an urgent necessity in the medical community.AIM To investigate the association of Sijunzi decoction plus chemotherapy with the gastrointestinal function and serum markers of patients after GC surgery.METHODS This study included patients who underwent GC surgery from June 2022 to February 2024.The control group included 45 patients who received chemotherapy(oxaliplatin+calcium folinate+5-fluorouracil),whereas the research group consisted of 54 patients who received Sijunzi decoction therapy in addition to the treatment administered in the control group.Comparative analyses were conducted from the following perspectives:Gastrointestinal function(defecation time,intestinal gas discharge time,and hospitalization time),serum markers[carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125,and CA199],nutritional indicators total protein(TP)and transferrin(TRF),traditional Chinese medicine(TCM)syndrome score,and grades Ⅲ–Ⅳ adverse events(gastrointestinal reactions,renal/liver function impairment,and myelosuppression).RESULTS The two groups demonstrated similar defecation time(P>0.05),but the intestinal gas discharge time and hospitalization time were significantly shortened in the research group(P<0.05).Further,the research group exhibited significant CEA,CA125,and CA199 reductions after treatment,which were lower compared to the control group,as well as notable increases in TP and TRF that were statistically higher than the control group(all P<0.05).Furthermore,the research group demonstrated an evident decrease in TCM syndrome scores in areas,such as poor appetite,epigastric distension and pain,fatigue and weakness(P<0.01),and abdominal distension after eating,which are notably lower than those in the control group(P<0.01),with a comparable incidence of grades Ⅲ-Ⅳ adverse events(P>0.05).CONCLUSION Our research results indicate that Sijunzi decoction plus chemotherapy exerts a good rehabilitation-promoting effect on gastrointestinal function in patients after GC surgery and significantly downregulates abnormally increased CEA,CA125,and CA199 levels.展开更多
The associations of polycyclic aromatic hydrocarbon(PAH)exposure with serum uric acid(SUA)or hyperuricemia have been rarely assessed.We aimed to investigate the relationships between urinary PAH metabolites and SUA or...The associations of polycyclic aromatic hydrocarbon(PAH)exposure with serum uric acid(SUA)or hyperuricemia have been rarely assessed.We aimed to investigate the relationships between urinary PAH metabolites and SUA or hyperuricemia among US adults and to explore the mediating role of systemic inflammation in the associations.A total of 10,307 US adults were conducted to assess the associations of seven urinary hydroxy–PAH with SUA and hyperuricemia and evaluate the role of C-reactive protein(CRP),a biomarker of systemic inflammation,in such associations.Results showed that each 1-unit increase in ln-transformed 2-hydroxynaphthalene(2-OHNa),1-hydroxyphenanthrene(1-OHPh),2&3-hydroxyphenanthrene(2&3-OHPh)and total hydroxyphenanthrene(OHPh)was associated with a 1.68(95%confidence interval(CI):0.19 to 3.17),2.46(0.78 to 4.13),3.34(1.59 to 5.09),and 2.99(1.23 to 4.75)μmol/L increase in SUA,and a 8%(odds ratio(OR):1.08,1.02 to 1.15),9%(OR:1.09,1.02 to 1.18),13%(OR:1.13,1.05 to 1.22),and 12%(OR:1.12,95%CI:1.03,1.21)increase in hyperuricemia,respectively.Co-exposure of seven PAHs was positively associated with SUA and hyperuricemia,with 2&3-OHPh showing the highest weight(components weights:0.83 and 0.78,respectively).The CRP mediated 11.47%and 10.44%of the associations ofΣOHPh and 2&3-OHPh with SUA and mediated 8.60%and 8.62%in associations ofΣOHPh and 2&3-OHPh with hyperuricemia,respectively.In conclusion,internal levels of PAH metabolites were associated with elevated SUA levels and the increased risk of hyperuricemia among US adults,and CRP played a mediating role in the associations.展开更多
BACKGROUND Laparoscopic surgery,with the advantage of less trauma,has been predominantly performed to treat pediatric inguinal hernia.However,the traditional three-port laparoscopic surgery remains extremely traumatic...BACKGROUND Laparoscopic surgery,with the advantage of less trauma,has been predominantly performed to treat pediatric inguinal hernia.However,the traditional three-port laparoscopic surgery remains extremely traumatic for children,whereas singleport laparoscopic surgery causes less damage to children than traditional laparoscopy.However,single-port laparoscopic surgery is more challenging;thus,studies on the effect of its application in pediatric inguinal hernia remain relatively limited.AIM To analyze the association of single-incision laparoscopic herniorrhaphy needle treatment with surgical outcomes,postoperative complications,and serum inflammation in pediatric inguinal hernia.METHODS This retrospective study included 113 pediatric patients with inguinal hernia who underwent surgery at the Children’s Hospital,Capital Institute of Pediatrics,from April 2022 to May 2023.Participants were categorized into the observation group(single-incision laparoscopic herniorrhaphy needle,n=60)and the control group(two-port laparoscopic surgery,n=53).Comparative analyses involved surgical duration,intraoperative blood loss,and length of hospital stay.C-reactive protein(CRP)and white blood cell count(WBC)levels were measured preoperatively and 24 hours postoperatively.Postoperative pain was evaluated with the face,legs,activity,cry,and Consolability scale.Further,the incidence of complications,recurrence,and reoperation rates was assessed.Logistic regression was employed to determine independent risk factors related to poor prognosis.RESULTS The observation group demonstrated significantly reduced intraoperative blood loss and shorter hospitalization compared to the control group(P<0.05).Both groups demonstrated increased CRP and WBC levels postoperatively,but the observation group exhibited significantly lower levels(P<0.05).Further,pain scores at 24 hours postoperatively were significantly lower in the observation group(P<0.05).Additionally,the observation group experienced fewer adverse events,recurrence rates,and reoperations compared to the control group(P<0.05).Logistic regression analysis determined increased postoperative stress markers and surgical technique as independent predictors of recurrence(P<0.05).CONCLUSION Single-incision laparoscopic herniorrhaphy needle treatment for pediatric inguinal hernia exhibits significant efficacy,effectively reduces postoperative complications,ensures a more concealed surgical incision,and promotes faster postoperative recovery than conventional two-port laparoscopy.This approach merits wider application.展开更多
Helicobacter pylori(H.pylori)infection induces pathological changes via chronic inflammation and virulence factors,thereby increasing the risk of gastric cancer development.Compared with invasive examination methods,H...Helicobacter pylori(H.pylori)infection induces pathological changes via chronic inflammation and virulence factors,thereby increasing the risk of gastric cancer development.Compared with invasive examination methods,H.pylori-related serum indicators are cost-effective and valuable for the early detection of gastric cancer(GC);however,large-scale clinical validation and sufficient understanding of the specific molecular mechanisms involved are lacking.Therefore,a comprehensive review and analysis of recent advances in this field is necessary.In this review,we systematically analyze the relationship between H.pylori and GC and discuss the application of new molecular biomarkers in GC screening.We also summarize the screening potential and application of anti-H.pylori immunoglobulin G and virulence factor-related serum antibodies for identifying GC risk.These indicators provide early warning of infection and enhance screening accuracy.Additionally,we discuss the potential combination of multiple screening indicators for the comprehensive analysis and development of emerging testing methods to improve the accuracy and efficiency of GC screening.Although this review may lack sufficient evidence due to limitations in existing studies,including small sample sizes,regional variations,and inconsistent testing methods,it contributes to advancing personalized precision medicine in high-risk populations and developing GC screening strategies.展开更多
BACKGROUND Rectal cancer requires accurate preoperative assessment of T stage and differentiation grade for treatment planning.Traditional imaging and serum markers have limitations in diagnostic accuracy.AIM To evalu...BACKGROUND Rectal cancer requires accurate preoperative assessment of T stage and differentiation grade for treatment planning.Traditional imaging and serum markers have limitations in diagnostic accuracy.AIM To evaluate the predictive value of dynamic contrast-enhanced-magnetic resonance imaging(DCE-MRI)parameters and serum biomarkers[carbohydrate antigen(CA)19-9,CA125]for determining T stage and differentiation grade in rectal cancer.METHODS We conducted a retrospective review of clinical data from 126 patients who were pathologically diagnosed with rectal cancer between January 2021 to June 2024.Each patient underwent DCE-MRI scans and serum tests for CA19-9 and CA125.Receiver operating characteristic curves were utilized to assess the diagnostic value of DCE-MRI parameters,including volume transfer constant(Ktrans),rate constant(Kep),and volume fraction of extravascular extracellular space(Ve),as well as serum biomarkers for staging and grading rectal cancer.The DeLong test algorithm was employed to evaluate differences in diagnostic performance among the various indicators.RESULTS There were statistically higher levels of Ktrans,Ve,CA19-9,and CA125 serum concentrations of patients with advanced T stages and on poorly differentiated tumors than that in patients with low stages and moderate to high differentiation(P<0.05).Combined use of Ktrans and Ve for T stage diagnosis showed an area under the curve(AUC)of 0.892[95%confidence interval(CI):0.832-0.952],which increased to 0.923(95%CI:0.865-0.981)when combined with serum biomarkers.For grades differentiation,the combined DCE-MRI parameters had an AUC of 0.883(95%CI:0.821-0.945),which rose to 0.912(95%CI:0.855-0.969)when combined with serum markers.According to the Delong test,the combined diagnostic method performed better than a single diagnostic method(P<0.05).CONCLUSION The combined application of DCE-MRI functional parameters and serum tumor markers can significantly improve the diagnostic accuracy of T staging and differentiation degree of rectal cancer,providing a new approach to improve the preoperative assessment system of rectal cancer.This combined diagnostic model has important clinical application value,but further validation is needed through large-scale multicenter studies.展开更多
Dear Editor,Local recurrence and cervical lymph node metastases are major causes of mortality in patients with head and neck squamous cell carcinoma(HNSCC).To date,none of the proposed strategies for predicting outcom...Dear Editor,Local recurrence and cervical lymph node metastases are major causes of mortality in patients with head and neck squamous cell carcinoma(HNSCC).To date,none of the proposed strategies for predicting outcomes in this disease have proven fully effective,and a comprehensive physical examination remains the primary method for early detection and monitoring of HNSCC.展开更多
BACKGROUND In recent years,metabolomics has emerged as a novel platform for biomarker discovery.However,the metabolic profiles associated with gastric carcinoma(GC)remain insufficiently explored.AIM To examine the dif...BACKGROUND In recent years,metabolomics has emerged as a novel platform for biomarker discovery.However,the metabolic profiles associated with gastric carcinoma(GC)remain insufficiently explored.AIM To examine the differences in metabolites between patients with GC and healthy controls,with the objective of identifying potential serum biomarkers for GC diagnosis through a non-targeted metabolomics approach.METHODS An untargeted metabolic analysis was conducted on serum samples from 6 patients with GC and 6 healthy controls.Subsequently,the differential metabolites identified were further validated in serum samples from an expanded cohort of 50 patients with GC and 50 healthy controls.The discriminative capacity of differential metabolites in distinguishing patients with GC from healthy controls was assessed utilizing the receiver operating characteristic curve analysis.The association between the serum levels of differential metabolites and the disease severity,as determined by the tumor-node-metastasis staging system,was evaluated using Spearman’s rank correlation coefficient.RESULTS Our findings revealed a significant alteration in the metabolic profile,characterized by 111 up-regulated and 55 down-regulated metabolites in patients with GC compared to healthy controls.Among the top 10 up-regulated metabolites,the serum concentrations of eight metabolites including fenpiclonil,methyclothiazide,5-hydroxyindoleacetate,3-pyridinecarboxylic acid,guanabenz,2,2-dichloro-N-(3-chloro-1,4-dioxo-2-naphthyl)acetamide,epigallocatechin gallate,and dimethenamid,were further validated to be significantly elevated in a cohort of 50 patients diagnosed with GC compared to 50 healthy control subjects(P<0.001).With the exception of 3-pyridinecarboxylic acid,the area under the curve values for the remaining seven metabolites exceeded 0.7,suggesting that these metabolites possess substantial diagnostic potential for distinguishing patients with GC from healthy individuals.Additionally,the serum concentrations of methyclothiazide(r=0.615,P<0.001),epigallocatechin gallate(r=0.482,P=0.004),and dimethenamid(r=0.634,P<0.001)demonstrated a significant positive correlation with the T stage in patients with GC.The serum concentrations of methyclothiazide(r=0.438,P=0.008)and epigallocatechin gallate(r=0.383,P=0.023)exhibited a significant positive correlation with the N stage in these patients.CONCLUSION This study provides insights into the metabolic alterations associated with GC,and the identification of these biomarkers may enhance the clinical detection and management of the disease.展开更多
BACKGROUND Exosomal microRNAs(miRNAs)have emerged as promising biomarkers for cancer diagnosis due to their stability,tumor specificity,and accessibility.How-ever,the diagnostic potential of serum exosomal miRNAs in m...BACKGROUND Exosomal microRNAs(miRNAs)have emerged as promising biomarkers for cancer diagnosis due to their stability,tumor specificity,and accessibility.How-ever,the diagnostic potential of serum exosomal miRNAs in metastatic pancreatic cancer remains underexplored.AIM To investigate the diagnostic potential of serum exosomal miRNAs in metastatic pancreatic cancer.METHODS A total of 36 patients were enrolled,comprising 8 patients in the discovery phase(4 with metastatic and 4 with non-metastatic pancreatic cancer)and 28 in the validation cohort(15 non-metastatic and 13 metastatic cases).Exosomes were isolated using the exoEasy Maxi Kit and characterized by transmission electron microscopy,nanoparticle tracking analysis,and western blotting.High-throu-ghput sequencing was conducted to identify differentially expressed serum exosomal miRNAs,which were subsequently validated using TaqMan probe-based reverse transcription-quantitative polymerase chain reaction.Bioinformatic analyses were performed to predict downstream target genes and explore their roles in metastatic progression.RESULTS Transmission electron microscopy revealed that the isolated exosomes were predominantly round or oval with well-defined membrane boundaries.Nano-particle tracking analysis showed a peak particle size of approximately 138 nm,accounting for 99.2%of total particles,consistent with the typical size range of exosomes.Western blotting confirmed the expression of exosome-specific markers CD63 and CD81.High-throughput sequencing identified 42 differentially expressed exosomal miRNAs between metastatic and non-metastatic groups.Among them,hsa-let-7f-5p was significantly upregulated in metastatic pancreatic cancer(P=0.007),as validated by reverse transcription-quantitative polymerase chain reaction.Target gene prediction indicated that hsa-let-7f-5p may be involved in metastasis through its interactions with nerve growth factor,cyclin-dependent kinase inhibitor 1A,high mobility group AT-hook 2,insulin-like growth factor 2 mRNA-binding protein 1,and insulin-like growth factor 2 mRNA-binding protein 3.CONCLUSION The elevated expression of serum exosomal hsa-let-7f-5p in metastatic pancreatic cancer suggests its potential as a non-invasive biomarker for distinguishing metastatic from non-metastatic disease.展开更多
BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnos...BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnosis.METHODS The study cohort comprised 50 patients diagnosed with GC and 50 healthy control subjects.A panel of 7 pro-inflammatory cytokines,including interleukin(IL)-1β,IL-2,IL-6,IL-8,IL-12,tumor necrosis factor-α,and interferon-γ(IFN-γ)were quantified using multiplex Luminex assays.Comparative analyses were conducted to evaluate cytokine levels between the GC patients and healthy controls.The diagnostic potential of serum pro-inflammatory cytokines in differentiating GC patients from healthy individuals was assessed through receiver operating characteristic(ROC)curve analysis.The correlation between serum cytokine levels and disease severity,as classified by the tumor-node-metastasis staging system,was analyzed using Spearman's rank correlation coefficient.RESULTS In comparison to the control group,patients with GC demonstrated significantly elevated serum levels of IL-1β(t=-4.089,P<0.001),IL-6(t=-3.983,P<0.001),IL8(t=-5.460,P<0.001),and IFN-γ(t=-2.856,P=0.005).ROC curve analysis indicated that the area under the curve values for IL-1β,IL-6,and IL-8 exceeded 0.7,effectively distinguishing GC patients from healthy controls.Additionally,serum levels of IL-1β(r=0.424,P=0.012)and IL-6(r=0.742,P<0.001)were positively correlated with the T stage in GC patients.Similarly,serum concentrations of IL-1β(r=0.356,P=0.039)and IL-6(r=0.441,P=0.008)exhibited a positive association with the N stage in these patients.CONCLUSION These findings suggest that circulating pro-inflammatory cytokines,such as IL-1β,IL-6,and IL-8,may serve as potential biomarkers for the diagnosis of GC.展开更多
Fructose consumption has risen dramatically in recent decades due to the use of sucrose and high fructose corn syrup in beverages and processed foods,contributing to rising rates of hyperuricemia.The purpose of this e...Fructose consumption has risen dramatically in recent decades due to the use of sucrose and high fructose corn syrup in beverages and processed foods,contributing to rising rates of hyperuricemia.The purpose of this experiment was to explore the anti-hyperuricemia effects of an active oligopeptide(GPSGRP)derived from sea cucumber in fructose induced hyperuricemia mouse model,and to clarify the underlying mechanism in sight of gut microbiota and serum metabolites.Peptide GPSGRP treatment rebalanced uric acid metabolism and alleviated inflammatory response in mice.In addition,treatment with GPSGRP decreased the abundance of Bacteroides and Proteobacteria at the phylum level,Muribaculum,Prevotella and Bacteroides at the genus level,and inhibited the related pathways of purine metabolism and glycolysis/gluconeogenesis metabolism.Moreover,serum metabolites,including linoleic acid,indole and its derivatives,arachidonic acid and uridine,as well as related metabolic pathways,such as tricarboxylic acid cycle,ketone production and sugar production,were altered in response to GPSGRP treatment.This study provides a valuable reference for the application and development of marine biological peptides in uric acid management.展开更多
The association of copper(Cu)with preterm birth(PTB)and its subtypes,spontaneous preterm birth(SPB)and iatrogenic preterm birth(IPB),are still unclear.In addition,previous studies suggested that serum lipid was associ...The association of copper(Cu)with preterm birth(PTB)and its subtypes,spontaneous preterm birth(SPB)and iatrogenic preterm birth(IPB),are still unclear.In addition,previous studies suggested that serum lipid was associated with both Cu and PTB.Therefore,we explored the association of blood Cu in the first trimester with the risk of PTB and its subtypes,as well as the potential mediating effect of serum lipid using a nested case-control study.The concentrations of Cu in the serum and blood cells,and serum lipids in the first trimester were measured.The concentration of Cu in whole blood was calculated based on hematocrit.Compared to the lowest tertile of Cu concentrations in the first trimester,the highest tertile of Cu significantly increased the risk of SPB with adjusted odds ratios(AORs)of 2.75(95% confidence interval(CI):1.41-5.34)for serum and 3.75(95% CI:1.21-11.60)for whole blood,and significantly increased the risk of IPB with AORs of 3.25(95%CI:1.06-9.94)for blood cells.According to the mediation analysis,the indirect effect of triglyceride(β=0.016,95%CI:0.0002-0.042)was the only significant effect in the association between Cu and SPB,with the mediating proportion of 9.8%(95%CI:0.2%-33.4%).It suggested that a high level of serum Cu may be associated with an increased risk of SPB with a possible mediator of serum triglyceride,and a high level of blood cell Cu may be associated with an increased risk of IPB.展开更多
BACKGROUND Current diagnostic standards for post-endoscopic retrograde cholangiopancreato-graphy(ERCP)pancreatitis(PEP)rely on 24-hour post-ERCP amylase and lipase levels,delaying timely intervention and highlighting ...BACKGROUND Current diagnostic standards for post-endoscopic retrograde cholangiopancreato-graphy(ERCP)pancreatitis(PEP)rely on 24-hour post-ERCP amylase and lipase levels,delaying timely intervention and highlighting the need for earlier predic-tive biomarkers.AIM To evaluate the utility of 4-hour post-ERCP serum amylase and lipase levels in a large cohort to establish optimal cut-off values and improve early PEP prediction.METHODS This prospective study involved patients with naïve major papillae who under-went diagnostic or therapeutic ERCP between June 2021 and December 2024.Serum amylase and lipase levels were measured before ERCP and 4 hours and 24 hours after ERCP.The primary endpoint was to determine optimal cut-off values for 4-hour serum amylase and lipase levels for the early prediction of PEP.RESULTS PEP occurred in 117 patients(6.1%).Diagnostic performance assessment of 4-hour serum amylase and lipase for predicting PEP yielded area under the curves of 0.877 and 0.893,respectively.Optimal cut-off values were 1.2 times the upper nor-mal limit(119.5 IU/L)for amylase and 8 times the upper normal limit(488.5 IU/L)for lipase.At these thresholds,4-hour amylase demonstrated a sensitivity of 0.846,a specificity of 0.806,and a negative predictive value of 0.988.Similarly,4-hour lipase showed a sensitivity of 0.863,a specificity of 0.862,and a negative predictive value of 0.990.These biomarkers effectively predicted moderately severe to severe PEP in high-risk groups.CONCLUSION Early measurement of 4-hour serum amylase and lipase shows strong predictive capabilities for PEP,with clinically meaningful cut-off values.These biomarkers enable timely interventions,potentially reducing PEP-related adverse events and the overall healthcare burden.展开更多
BACKGROUND Serum calcium ion(Ca2+)is an economical and readily available indicator as a routine screening test for hospitalized patients.There are no studies related to serum Ca2+level and digestive tract malignancy.A...BACKGROUND Serum calcium ion(Ca2+)is an economical and readily available indicator as a routine screening test for hospitalized patients.There are no studies related to serum Ca2+level and digestive tract malignancy.AIM To evaluate the effectiveness of serum Ca2+level in predicting the prognosis of patients with colorectal cancer(CRC).METHODS We retrospectively collected the data of 280 patients diagnosed with CRC who underwent radical surgery at the Affiliated Cancer Hospital of Xinjiang Medical University.By analyzing the clinicopathological features,differences between serum Ca2+concentrations on the first day after surgery were determined.We used the receiver operating characteristic curve to assess the predictive ability of serum Ca2+for survival.Survival analyses were performed using the Kaplan-Meier method,and multivariate Cox proportional risk regression was used to determine association between calibration serum Ca2+levels and CRC survival outcomes.RESULTS By receiver operating characteristic curve analysis,the ideal threshold value for Ca2+the first postoperative day and delta serum calcium(δCa2+)value were 1.975 and 0.245,respectively.Overall survival(OS)and progression-free survival(PFS)were better in both the high Ca2+group and highδCa2+group on the first postoperative day.The variables identified through univariate analysis were incorporated into multivariate analysis and showed that tumor differ-entiation(P=0.047),T stage(P=0.019),N stage(P<0.001),nerve vascular invasion(P=0.037),carcinoembryonic antigen(P=0.039),baseline serum Ca2+level(P=0.011),and serum Ca2+level on the first day(P=0.006)were independent predictors of prognosis for patients undergoing feasible radical CRC surgery.Using the findings from the multifactorial analysis,we developed a nomogram and the calibration showed a good predictive ability.CONCLUSION Low serum Ca2+level on the first postoperative day is an independent risk factor for OS and PFS in CRC.展开更多
BACKGROUND Splenectomy is an effective yet invasive intervention for alleviating portal pressure in patients with hepatitis cirrhosis.However,the current prognostic indicators for predicting long-term overall survival...BACKGROUND Splenectomy is an effective yet invasive intervention for alleviating portal pressure in patients with hepatitis cirrhosis.However,the current prognostic indicators for predicting long-term overall survival of these patients have several limitations.AIM To assess the potential of preoperative total bilirubin-albumin(B/A)ratio as a prognostic indicator for patients with hepatitis cirrhosis undergoing splenectomy.METHODS A total of 257 patients diagnosed with hepatitis cirrhosis were retrospectively enrolled in the study.Normality test,t-test,Wilcoxon test,χ2 test,or Fisher’s exact test was employed to analyze the intraoperative and postoperative conditions of the patients.Receiver operating characteristic(ROC)curve analysis was utilized to depict the 10-year overall survival rate.RESULTS During the follow-up period,85.99%of the patients survived,with a median survival time of 64.6 months.Multivariate analysis revealed that total serum B/A ratio was an independent risk factor for overall survival(P=0.037).ROC curve analysis demonstrated that a B/A ratio of 0.87 was the optimal cut-off value.Consequently,the patients were categorized into two groups:High B/A group(n=64)and low B/A group(n=193).The median follow-up time for the high B/A group and low B/A group was 56.8 months and 67.2 months,respectively(P=0.045).Notably,the high B/A group exhibited a significantly lower 10-year overall survival compared to the low B/A group(P<0.001).Patients with hepatocellular carcinoma(HCC)had lower overall survival rates.Patients with a high B/A ratio exhibited a lower overall survival than those with a low B/A rate in the overall cohort and the subgroups of patients with HCC or not,early Child-Pugh grade,low albumin-bilirubin grade,and model for end-stage liver disease score≥10(log-rank test,P<0.001 for all).CONCLUSION The B/A ratio can serve as an effective prognostic indicator for overall survival in patients with hepatitis B virusrelated cirrhosis following splenectomy,and a higher B/A ratio may suggest a poorer prognosis.展开更多
BACKGROUND Serum carcinoembryonic antigen(CEA)levels and magnetic resonance imaging(MRI)findings are widely used for the diagnosis and treatment of rectal cancer;however,research investigating their correlation remain...BACKGROUND Serum carcinoembryonic antigen(CEA)levels and magnetic resonance imaging(MRI)findings are widely used for the diagnosis and treatment of rectal cancer;however,research investigating their correlation remains limited.AIM To investigate the correlation between baseline MRI features and serum CEA levels in patients diagnosed with primary rectal cancer.METHODS Eighty patients(age:42-78 years)diagnosed with primary rectal cancer were enrolled.Baseline MRI examinations were performed to evaluate tumor size,T stage,circumferential resection margin status,extramural vascular invasion(EMVI),and lymph node metastasis.Serum CEA levels were concurrently measured.Statistical methods were used to analyze correlations.RESULTS Tumor size,T stage,EMVI,and lymph node metastasis were significantly correlated with serum CEA levels(P<0.05).Multivariate analysis identified T stage and lymph node metastasis as independent factors influencing serum CEA levels.CONCLUSION This study confirmed the correlation between baseline MRI features and serum CEA levels in patients with primary rectal cancer,highlighting their potential utility for precise diagnosis,staging,and prognostic evaluation.展开更多
基金supported by the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-055)the National Natural Science Foundation of China(82471925)。
文摘The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to represent human chronic AC administrations for 13 days.Organ pathology was determined using hematoxylin-eosin staining and immunohistochemistry.Fecal and proximal intestinal content samples were collected to perform shotgun metagenomic sequencing.Serum samples were collected,and untargeted metabolomics was performed.In this study,AC administration induced proximal intestine,liver,and kidney injury.Microbiome composition remained stable after AC exposure,while several microbes presented dynamic alteration.Moreover,AC affected the abundance of the fatty acid biosynthesis rate-limiting gene acc A at day 7.AC induces 30 serum metabolites to significantly change at day 14,including several short-chain acylcarnitines.WGCNA revealed 2 sub-modules associated with the level of several short-chain acylcarnitines.In summary,AC affects the digestive tract and serum metabolism after chronic administration.AC may affect the enrichment of microbial-derived acc A gene.The abundance of serum acylcarnitines detected in the AC group may associate with its anti-heart failure effects.
基金funded by the Shenzhen Science and Technology Program(JCYJ20230807112007014 to PG)the Shenzhen Key Medical Discipline Construction Fund(SZXK046 to PG).
文摘BACKGROUND:Serum osmolality is a prognostic indicator in critically ill patients.This study aimed to evaluate the association between high osmolality and 28-day mortality in patients with cardiac arrest(CA)admitted to the intensive care unit(ICU).METHODS:Baseline data of adult patients with CA who were admitted to the ICU from 2008 to 2019 were collected from the Medical Information Mart for Intensive Care(MIMIC)-IV.Patients were divided into survivor and non-survivor groups according to the 28-day prognosis.Serum concentrations of sodium,potassium,glucose,and urea nitrogen on the fi rst day of ICU admission were used to determine serum osmolarity.The primary endpoint of this study was 28-day all-cause mortality.Propensity score matching(PSM)analysis was performed to reduce bias between the survivor and nonsurvivor groups.RESULTS:Among the 798 included CA patients,the high osmolarity on the first day of ICU admission remained significantly associated with increased 28-day mortality(62.0%vs.35.5%,P<0.001)and reduced cumulative survival(log-rank P<0.05)after PSM.Cox regression identifi ed the high osmolarity on the fi rst day of ICU admission as an independent predictor.High serum osmolarity on the fi rst day of ICU admission eff ectively predicted 1-,3-,7-,and 28-day all-cause mortality,with the strongest predictive performance for 1-day mortality both before and after PSM(all P<0.05).CONCLUSION:In this study,elevated serum osmolarity on the first day of ICU admission was independently associated with increased 28-day mortality in CA patients and could serve as a prognostic marker.
基金Supported by the Central High Level Hospital Clinical Research Funding(No.BJ-2024-089).
文摘AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.
基金part of the EU consortium DCog Plast ‘Diet Cognition and Plasticity” funded by the Joint Programming Initiative “A Health Diet for a Healthy Life”(JPI-HDHL) via the BMWFW (BMWFW-10.420/0009-WF/V/3c/2015 and the Medical Research Council UK:MR/N030087/1)(to LA and ST)supported by the PMU-FFF Research Fund (A-16/01/019-AIG)+9 种基金BA by the PMU-Research and Innovation Fund (PMU-RIF)(project 2023-PRE-008-Altendorfer)supported by the Center for Urban Mental Healthby Alzheimer Nederlandthe Zon MW Program Mechanisms Of DEMentia (MODEM)by the Gravitation program iCNS of the Dutch Research Council (NWO)supported by Grant PID2020-114921RB-C21Maria de Maeztu Unit of Excellence grant CEX2021-001234-M funded by MCIU/AEI/and CIBERFESCB16/10/00269, from the Instituto de Salud Carlos III all of them by “ERDF A way of making Europe”the Generalitat de Catalunya’s Agency AGAUR of 2021SGR00687ICREA Award
文摘In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.
基金supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2017-12M-3-002)the Central High Level Hospital Clinical Research Operating Expenses,China(Zero Balance 2022-GSP-GG-15)the Natural Science Foundation Project of the Inner Mongolia Autonomous Region of China(2022LHQN08003).
文摘BACKGROUND Low serum albumin levels are established predictors of adverse outcomes in various cardiovascular conditions.However,the role of serum albumin in mortality among elderly patients with chronic aortic regurgitation(AR)has not been thoroughly investigated.This study aims to assess the relationship between serum albumin levels and mortality in this specific patient population.METHODS Our analysis included 873 elderly AR patients from the China Valvular Heart Disease study,with baseline serum albumin measured at enrollment.Mortality outcomes were monitored for two years post-enrollment,employing a Cox proportional hazards model with a two-piecewise Cox proportional hazards framework to investigate the nonlinear relationship between serum albumin levels and all-cause mortality.RESULTS During the 2-year follow-up period,we observed 63 all-cause deaths.The association between serum albumin levels and all-cause mortality displayed an approximating L-shaped curve,indicating a mortality threshold at 35 g/L.For serum albumin levels below 35 g/L,each 1 g/L decrease was associated with a 25%higher risk of all-cause mortality(HR=1.25,95%CI:1.07–1.45).In contrast,no significant change in mortality risk was observed when serum albumin levels were greater than or equal to 35 g/L.Moreover,when serum albumin is classified as hypoproteinemia(serum albumin<35 g/L),the higher risks of all-cause death were observed in hypoproteinemic patients(HR=2.93,95%CI:1.50–5.74).More importantly,the association between serum albumin and death was significantly stronger in overweight/obese patients(≥24 kg/m^(2)vs.<24 kg/m^(2),Pinteraction=0.006).CONCLUSIONS In elderly patients with AR,serum albumin levels showed an approximating L-shaped relationship with all-cause death,with thresholds of 35 g/L.Body mass index was significant effect modifiers of the association.These results suggest that serum albumin,as an inexpensive and readily available biochemical marker,may further improve the stratified risk of mortality in older AR patients.
基金Supported by Liaoning Provincial Science and Technology Plan Joint Plan,No.2023JH2/101700149。
文摘BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer(GC)resection despite the substantial curative benefits provided by surgical interventions for GC.Hence,the investigation of more optimal and efficacious treatment approaches has become an urgent necessity in the medical community.AIM To investigate the association of Sijunzi decoction plus chemotherapy with the gastrointestinal function and serum markers of patients after GC surgery.METHODS This study included patients who underwent GC surgery from June 2022 to February 2024.The control group included 45 patients who received chemotherapy(oxaliplatin+calcium folinate+5-fluorouracil),whereas the research group consisted of 54 patients who received Sijunzi decoction therapy in addition to the treatment administered in the control group.Comparative analyses were conducted from the following perspectives:Gastrointestinal function(defecation time,intestinal gas discharge time,and hospitalization time),serum markers[carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125,and CA199],nutritional indicators total protein(TP)and transferrin(TRF),traditional Chinese medicine(TCM)syndrome score,and grades Ⅲ–Ⅳ adverse events(gastrointestinal reactions,renal/liver function impairment,and myelosuppression).RESULTS The two groups demonstrated similar defecation time(P>0.05),but the intestinal gas discharge time and hospitalization time were significantly shortened in the research group(P<0.05).Further,the research group exhibited significant CEA,CA125,and CA199 reductions after treatment,which were lower compared to the control group,as well as notable increases in TP and TRF that were statistically higher than the control group(all P<0.05).Furthermore,the research group demonstrated an evident decrease in TCM syndrome scores in areas,such as poor appetite,epigastric distension and pain,fatigue and weakness(P<0.01),and abdominal distension after eating,which are notably lower than those in the control group(P<0.01),with a comparable incidence of grades Ⅲ-Ⅳ adverse events(P>0.05).CONCLUSION Our research results indicate that Sijunzi decoction plus chemotherapy exerts a good rehabilitation-promoting effect on gastrointestinal function in patients after GC surgery and significantly downregulates abnormally increased CEA,CA125,and CA199 levels.
基金supported by the Key Program of National Natural Science Foundation of China(No.82241088)the Natural Science Foundation of Hubei Province(No.2022CFB813).
文摘The associations of polycyclic aromatic hydrocarbon(PAH)exposure with serum uric acid(SUA)or hyperuricemia have been rarely assessed.We aimed to investigate the relationships between urinary PAH metabolites and SUA or hyperuricemia among US adults and to explore the mediating role of systemic inflammation in the associations.A total of 10,307 US adults were conducted to assess the associations of seven urinary hydroxy–PAH with SUA and hyperuricemia and evaluate the role of C-reactive protein(CRP),a biomarker of systemic inflammation,in such associations.Results showed that each 1-unit increase in ln-transformed 2-hydroxynaphthalene(2-OHNa),1-hydroxyphenanthrene(1-OHPh),2&3-hydroxyphenanthrene(2&3-OHPh)and total hydroxyphenanthrene(OHPh)was associated with a 1.68(95%confidence interval(CI):0.19 to 3.17),2.46(0.78 to 4.13),3.34(1.59 to 5.09),and 2.99(1.23 to 4.75)μmol/L increase in SUA,and a 8%(odds ratio(OR):1.08,1.02 to 1.15),9%(OR:1.09,1.02 to 1.18),13%(OR:1.13,1.05 to 1.22),and 12%(OR:1.12,95%CI:1.03,1.21)increase in hyperuricemia,respectively.Co-exposure of seven PAHs was positively associated with SUA and hyperuricemia,with 2&3-OHPh showing the highest weight(components weights:0.83 and 0.78,respectively).The CRP mediated 11.47%and 10.44%of the associations ofΣOHPh and 2&3-OHPh with SUA and mediated 8.60%and 8.62%in associations ofΣOHPh and 2&3-OHPh with hyperuricemia,respectively.In conclusion,internal levels of PAH metabolites were associated with elevated SUA levels and the increased risk of hyperuricemia among US adults,and CRP played a mediating role in the associations.
基金Supported by Research Unit of Minimally Invasive Pediatric Surgery on Diagnosis and Treatment,Chinese Academy of Medical Sciences,No.2021RU016.
文摘BACKGROUND Laparoscopic surgery,with the advantage of less trauma,has been predominantly performed to treat pediatric inguinal hernia.However,the traditional three-port laparoscopic surgery remains extremely traumatic for children,whereas singleport laparoscopic surgery causes less damage to children than traditional laparoscopy.However,single-port laparoscopic surgery is more challenging;thus,studies on the effect of its application in pediatric inguinal hernia remain relatively limited.AIM To analyze the association of single-incision laparoscopic herniorrhaphy needle treatment with surgical outcomes,postoperative complications,and serum inflammation in pediatric inguinal hernia.METHODS This retrospective study included 113 pediatric patients with inguinal hernia who underwent surgery at the Children’s Hospital,Capital Institute of Pediatrics,from April 2022 to May 2023.Participants were categorized into the observation group(single-incision laparoscopic herniorrhaphy needle,n=60)and the control group(two-port laparoscopic surgery,n=53).Comparative analyses involved surgical duration,intraoperative blood loss,and length of hospital stay.C-reactive protein(CRP)and white blood cell count(WBC)levels were measured preoperatively and 24 hours postoperatively.Postoperative pain was evaluated with the face,legs,activity,cry,and Consolability scale.Further,the incidence of complications,recurrence,and reoperation rates was assessed.Logistic regression was employed to determine independent risk factors related to poor prognosis.RESULTS The observation group demonstrated significantly reduced intraoperative blood loss and shorter hospitalization compared to the control group(P<0.05).Both groups demonstrated increased CRP and WBC levels postoperatively,but the observation group exhibited significantly lower levels(P<0.05).Further,pain scores at 24 hours postoperatively were significantly lower in the observation group(P<0.05).Additionally,the observation group experienced fewer adverse events,recurrence rates,and reoperations compared to the control group(P<0.05).Logistic regression analysis determined increased postoperative stress markers and surgical technique as independent predictors of recurrence(P<0.05).CONCLUSION Single-incision laparoscopic herniorrhaphy needle treatment for pediatric inguinal hernia exhibits significant efficacy,effectively reduces postoperative complications,ensures a more concealed surgical incision,and promotes faster postoperative recovery than conventional two-port laparoscopy.This approach merits wider application.
文摘Helicobacter pylori(H.pylori)infection induces pathological changes via chronic inflammation and virulence factors,thereby increasing the risk of gastric cancer development.Compared with invasive examination methods,H.pylori-related serum indicators are cost-effective and valuable for the early detection of gastric cancer(GC);however,large-scale clinical validation and sufficient understanding of the specific molecular mechanisms involved are lacking.Therefore,a comprehensive review and analysis of recent advances in this field is necessary.In this review,we systematically analyze the relationship between H.pylori and GC and discuss the application of new molecular biomarkers in GC screening.We also summarize the screening potential and application of anti-H.pylori immunoglobulin G and virulence factor-related serum antibodies for identifying GC risk.These indicators provide early warning of infection and enhance screening accuracy.Additionally,we discuss the potential combination of multiple screening indicators for the comprehensive analysis and development of emerging testing methods to improve the accuracy and efficiency of GC screening.Although this review may lack sufficient evidence due to limitations in existing studies,including small sample sizes,regional variations,and inconsistent testing methods,it contributes to advancing personalized precision medicine in high-risk populations and developing GC screening strategies.
文摘BACKGROUND Rectal cancer requires accurate preoperative assessment of T stage and differentiation grade for treatment planning.Traditional imaging and serum markers have limitations in diagnostic accuracy.AIM To evaluate the predictive value of dynamic contrast-enhanced-magnetic resonance imaging(DCE-MRI)parameters and serum biomarkers[carbohydrate antigen(CA)19-9,CA125]for determining T stage and differentiation grade in rectal cancer.METHODS We conducted a retrospective review of clinical data from 126 patients who were pathologically diagnosed with rectal cancer between January 2021 to June 2024.Each patient underwent DCE-MRI scans and serum tests for CA19-9 and CA125.Receiver operating characteristic curves were utilized to assess the diagnostic value of DCE-MRI parameters,including volume transfer constant(Ktrans),rate constant(Kep),and volume fraction of extravascular extracellular space(Ve),as well as serum biomarkers for staging and grading rectal cancer.The DeLong test algorithm was employed to evaluate differences in diagnostic performance among the various indicators.RESULTS There were statistically higher levels of Ktrans,Ve,CA19-9,and CA125 serum concentrations of patients with advanced T stages and on poorly differentiated tumors than that in patients with low stages and moderate to high differentiation(P<0.05).Combined use of Ktrans and Ve for T stage diagnosis showed an area under the curve(AUC)of 0.892[95%confidence interval(CI):0.832-0.952],which increased to 0.923(95%CI:0.865-0.981)when combined with serum biomarkers.For grades differentiation,the combined DCE-MRI parameters had an AUC of 0.883(95%CI:0.821-0.945),which rose to 0.912(95%CI:0.855-0.969)when combined with serum markers.According to the Delong test,the combined diagnostic method performed better than a single diagnostic method(P<0.05).CONCLUSION The combined application of DCE-MRI functional parameters and serum tumor markers can significantly improve the diagnostic accuracy of T staging and differentiation degree of rectal cancer,providing a new approach to improve the preoperative assessment system of rectal cancer.This combined diagnostic model has important clinical application value,but further validation is needed through large-scale multicenter studies.
文摘Dear Editor,Local recurrence and cervical lymph node metastases are major causes of mortality in patients with head and neck squamous cell carcinoma(HNSCC).To date,none of the proposed strategies for predicting outcomes in this disease have proven fully effective,and a comprehensive physical examination remains the primary method for early detection and monitoring of HNSCC.
文摘BACKGROUND In recent years,metabolomics has emerged as a novel platform for biomarker discovery.However,the metabolic profiles associated with gastric carcinoma(GC)remain insufficiently explored.AIM To examine the differences in metabolites between patients with GC and healthy controls,with the objective of identifying potential serum biomarkers for GC diagnosis through a non-targeted metabolomics approach.METHODS An untargeted metabolic analysis was conducted on serum samples from 6 patients with GC and 6 healthy controls.Subsequently,the differential metabolites identified were further validated in serum samples from an expanded cohort of 50 patients with GC and 50 healthy controls.The discriminative capacity of differential metabolites in distinguishing patients with GC from healthy controls was assessed utilizing the receiver operating characteristic curve analysis.The association between the serum levels of differential metabolites and the disease severity,as determined by the tumor-node-metastasis staging system,was evaluated using Spearman’s rank correlation coefficient.RESULTS Our findings revealed a significant alteration in the metabolic profile,characterized by 111 up-regulated and 55 down-regulated metabolites in patients with GC compared to healthy controls.Among the top 10 up-regulated metabolites,the serum concentrations of eight metabolites including fenpiclonil,methyclothiazide,5-hydroxyindoleacetate,3-pyridinecarboxylic acid,guanabenz,2,2-dichloro-N-(3-chloro-1,4-dioxo-2-naphthyl)acetamide,epigallocatechin gallate,and dimethenamid,were further validated to be significantly elevated in a cohort of 50 patients diagnosed with GC compared to 50 healthy control subjects(P<0.001).With the exception of 3-pyridinecarboxylic acid,the area under the curve values for the remaining seven metabolites exceeded 0.7,suggesting that these metabolites possess substantial diagnostic potential for distinguishing patients with GC from healthy individuals.Additionally,the serum concentrations of methyclothiazide(r=0.615,P<0.001),epigallocatechin gallate(r=0.482,P=0.004),and dimethenamid(r=0.634,P<0.001)demonstrated a significant positive correlation with the T stage in patients with GC.The serum concentrations of methyclothiazide(r=0.438,P=0.008)and epigallocatechin gallate(r=0.383,P=0.023)exhibited a significant positive correlation with the N stage in these patients.CONCLUSION This study provides insights into the metabolic alterations associated with GC,and the identification of these biomarkers may enhance the clinical detection and management of the disease.
文摘BACKGROUND Exosomal microRNAs(miRNAs)have emerged as promising biomarkers for cancer diagnosis due to their stability,tumor specificity,and accessibility.How-ever,the diagnostic potential of serum exosomal miRNAs in metastatic pancreatic cancer remains underexplored.AIM To investigate the diagnostic potential of serum exosomal miRNAs in metastatic pancreatic cancer.METHODS A total of 36 patients were enrolled,comprising 8 patients in the discovery phase(4 with metastatic and 4 with non-metastatic pancreatic cancer)and 28 in the validation cohort(15 non-metastatic and 13 metastatic cases).Exosomes were isolated using the exoEasy Maxi Kit and characterized by transmission electron microscopy,nanoparticle tracking analysis,and western blotting.High-throu-ghput sequencing was conducted to identify differentially expressed serum exosomal miRNAs,which were subsequently validated using TaqMan probe-based reverse transcription-quantitative polymerase chain reaction.Bioinformatic analyses were performed to predict downstream target genes and explore their roles in metastatic progression.RESULTS Transmission electron microscopy revealed that the isolated exosomes were predominantly round or oval with well-defined membrane boundaries.Nano-particle tracking analysis showed a peak particle size of approximately 138 nm,accounting for 99.2%of total particles,consistent with the typical size range of exosomes.Western blotting confirmed the expression of exosome-specific markers CD63 and CD81.High-throughput sequencing identified 42 differentially expressed exosomal miRNAs between metastatic and non-metastatic groups.Among them,hsa-let-7f-5p was significantly upregulated in metastatic pancreatic cancer(P=0.007),as validated by reverse transcription-quantitative polymerase chain reaction.Target gene prediction indicated that hsa-let-7f-5p may be involved in metastasis through its interactions with nerve growth factor,cyclin-dependent kinase inhibitor 1A,high mobility group AT-hook 2,insulin-like growth factor 2 mRNA-binding protein 1,and insulin-like growth factor 2 mRNA-binding protein 3.CONCLUSION The elevated expression of serum exosomal hsa-let-7f-5p in metastatic pancreatic cancer suggests its potential as a non-invasive biomarker for distinguishing metastatic from non-metastatic disease.
文摘BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnosis.METHODS The study cohort comprised 50 patients diagnosed with GC and 50 healthy control subjects.A panel of 7 pro-inflammatory cytokines,including interleukin(IL)-1β,IL-2,IL-6,IL-8,IL-12,tumor necrosis factor-α,and interferon-γ(IFN-γ)were quantified using multiplex Luminex assays.Comparative analyses were conducted to evaluate cytokine levels between the GC patients and healthy controls.The diagnostic potential of serum pro-inflammatory cytokines in differentiating GC patients from healthy individuals was assessed through receiver operating characteristic(ROC)curve analysis.The correlation between serum cytokine levels and disease severity,as classified by the tumor-node-metastasis staging system,was analyzed using Spearman's rank correlation coefficient.RESULTS In comparison to the control group,patients with GC demonstrated significantly elevated serum levels of IL-1β(t=-4.089,P<0.001),IL-6(t=-3.983,P<0.001),IL8(t=-5.460,P<0.001),and IFN-γ(t=-2.856,P=0.005).ROC curve analysis indicated that the area under the curve values for IL-1β,IL-6,and IL-8 exceeded 0.7,effectively distinguishing GC patients from healthy controls.Additionally,serum levels of IL-1β(r=0.424,P=0.012)and IL-6(r=0.742,P<0.001)were positively correlated with the T stage in GC patients.Similarly,serum concentrations of IL-1β(r=0.356,P=0.039)and IL-6(r=0.441,P=0.008)exhibited a positive association with the N stage in these patients.CONCLUSION These findings suggest that circulating pro-inflammatory cytokines,such as IL-1β,IL-6,and IL-8,may serve as potential biomarkers for the diagnosis of GC.
基金sponsored by the One Health Interdisciplinary Research Project,Ningbo University,Open Fund of Key Laboratory of Aquacultural Biotechnology Ministry of Education in Ningbo University,and K.C.Wong Magna Fund of Ningbo Universitythe National Natural Science Foundation China(32270115)+1 种基金National Key R&D Program of China(2018YFD0901102)Fundamental Research Funds for the Provincial Universities of Zhejiang(SJLY2021015)。
文摘Fructose consumption has risen dramatically in recent decades due to the use of sucrose and high fructose corn syrup in beverages and processed foods,contributing to rising rates of hyperuricemia.The purpose of this experiment was to explore the anti-hyperuricemia effects of an active oligopeptide(GPSGRP)derived from sea cucumber in fructose induced hyperuricemia mouse model,and to clarify the underlying mechanism in sight of gut microbiota and serum metabolites.Peptide GPSGRP treatment rebalanced uric acid metabolism and alleviated inflammatory response in mice.In addition,treatment with GPSGRP decreased the abundance of Bacteroides and Proteobacteria at the phylum level,Muribaculum,Prevotella and Bacteroides at the genus level,and inhibited the related pathways of purine metabolism and glycolysis/gluconeogenesis metabolism.Moreover,serum metabolites,including linoleic acid,indole and its derivatives,arachidonic acid and uridine,as well as related metabolic pathways,such as tricarboxylic acid cycle,ketone production and sugar production,were altered in response to GPSGRP treatment.This study provides a valuable reference for the application and development of marine biological peptides in uric acid management.
基金supported by Beijing Natural Science Foundation(No.7222248)the National Natural Science Foundation of China(No.81673177).
文摘The association of copper(Cu)with preterm birth(PTB)and its subtypes,spontaneous preterm birth(SPB)and iatrogenic preterm birth(IPB),are still unclear.In addition,previous studies suggested that serum lipid was associated with both Cu and PTB.Therefore,we explored the association of blood Cu in the first trimester with the risk of PTB and its subtypes,as well as the potential mediating effect of serum lipid using a nested case-control study.The concentrations of Cu in the serum and blood cells,and serum lipids in the first trimester were measured.The concentration of Cu in whole blood was calculated based on hematocrit.Compared to the lowest tertile of Cu concentrations in the first trimester,the highest tertile of Cu significantly increased the risk of SPB with adjusted odds ratios(AORs)of 2.75(95% confidence interval(CI):1.41-5.34)for serum and 3.75(95% CI:1.21-11.60)for whole blood,and significantly increased the risk of IPB with AORs of 3.25(95%CI:1.06-9.94)for blood cells.According to the mediation analysis,the indirect effect of triglyceride(β=0.016,95%CI:0.0002-0.042)was the only significant effect in the association between Cu and SPB,with the mediating proportion of 9.8%(95%CI:0.2%-33.4%).It suggested that a high level of serum Cu may be associated with an increased risk of SPB with a possible mediator of serum triglyceride,and a high level of blood cell Cu may be associated with an increased risk of IPB.
基金Supported by National Research Foundation of Korea,No.NFR-2022R1C1C1006242the Hallym University Medical Center Research Fund.
文摘BACKGROUND Current diagnostic standards for post-endoscopic retrograde cholangiopancreato-graphy(ERCP)pancreatitis(PEP)rely on 24-hour post-ERCP amylase and lipase levels,delaying timely intervention and highlighting the need for earlier predic-tive biomarkers.AIM To evaluate the utility of 4-hour post-ERCP serum amylase and lipase levels in a large cohort to establish optimal cut-off values and improve early PEP prediction.METHODS This prospective study involved patients with naïve major papillae who under-went diagnostic or therapeutic ERCP between June 2021 and December 2024.Serum amylase and lipase levels were measured before ERCP and 4 hours and 24 hours after ERCP.The primary endpoint was to determine optimal cut-off values for 4-hour serum amylase and lipase levels for the early prediction of PEP.RESULTS PEP occurred in 117 patients(6.1%).Diagnostic performance assessment of 4-hour serum amylase and lipase for predicting PEP yielded area under the curves of 0.877 and 0.893,respectively.Optimal cut-off values were 1.2 times the upper nor-mal limit(119.5 IU/L)for amylase and 8 times the upper normal limit(488.5 IU/L)for lipase.At these thresholds,4-hour amylase demonstrated a sensitivity of 0.846,a specificity of 0.806,and a negative predictive value of 0.988.Similarly,4-hour lipase showed a sensitivity of 0.863,a specificity of 0.862,and a negative predictive value of 0.990.These biomarkers effectively predicted moderately severe to severe PEP in high-risk groups.CONCLUSION Early measurement of 4-hour serum amylase and lipase shows strong predictive capabilities for PEP,with clinically meaningful cut-off values.These biomarkers enable timely interventions,potentially reducing PEP-related adverse events and the overall healthcare burden.
文摘BACKGROUND Serum calcium ion(Ca2+)is an economical and readily available indicator as a routine screening test for hospitalized patients.There are no studies related to serum Ca2+level and digestive tract malignancy.AIM To evaluate the effectiveness of serum Ca2+level in predicting the prognosis of patients with colorectal cancer(CRC).METHODS We retrospectively collected the data of 280 patients diagnosed with CRC who underwent radical surgery at the Affiliated Cancer Hospital of Xinjiang Medical University.By analyzing the clinicopathological features,differences between serum Ca2+concentrations on the first day after surgery were determined.We used the receiver operating characteristic curve to assess the predictive ability of serum Ca2+for survival.Survival analyses were performed using the Kaplan-Meier method,and multivariate Cox proportional risk regression was used to determine association between calibration serum Ca2+levels and CRC survival outcomes.RESULTS By receiver operating characteristic curve analysis,the ideal threshold value for Ca2+the first postoperative day and delta serum calcium(δCa2+)value were 1.975 and 0.245,respectively.Overall survival(OS)and progression-free survival(PFS)were better in both the high Ca2+group and highδCa2+group on the first postoperative day.The variables identified through univariate analysis were incorporated into multivariate analysis and showed that tumor differ-entiation(P=0.047),T stage(P=0.019),N stage(P<0.001),nerve vascular invasion(P=0.037),carcinoembryonic antigen(P=0.039),baseline serum Ca2+level(P=0.011),and serum Ca2+level on the first day(P=0.006)were independent predictors of prognosis for patients undergoing feasible radical CRC surgery.Using the findings from the multifactorial analysis,we developed a nomogram and the calibration showed a good predictive ability.CONCLUSION Low serum Ca2+level on the first postoperative day is an independent risk factor for OS and PFS in CRC.
文摘BACKGROUND Splenectomy is an effective yet invasive intervention for alleviating portal pressure in patients with hepatitis cirrhosis.However,the current prognostic indicators for predicting long-term overall survival of these patients have several limitations.AIM To assess the potential of preoperative total bilirubin-albumin(B/A)ratio as a prognostic indicator for patients with hepatitis cirrhosis undergoing splenectomy.METHODS A total of 257 patients diagnosed with hepatitis cirrhosis were retrospectively enrolled in the study.Normality test,t-test,Wilcoxon test,χ2 test,or Fisher’s exact test was employed to analyze the intraoperative and postoperative conditions of the patients.Receiver operating characteristic(ROC)curve analysis was utilized to depict the 10-year overall survival rate.RESULTS During the follow-up period,85.99%of the patients survived,with a median survival time of 64.6 months.Multivariate analysis revealed that total serum B/A ratio was an independent risk factor for overall survival(P=0.037).ROC curve analysis demonstrated that a B/A ratio of 0.87 was the optimal cut-off value.Consequently,the patients were categorized into two groups:High B/A group(n=64)and low B/A group(n=193).The median follow-up time for the high B/A group and low B/A group was 56.8 months and 67.2 months,respectively(P=0.045).Notably,the high B/A group exhibited a significantly lower 10-year overall survival compared to the low B/A group(P<0.001).Patients with hepatocellular carcinoma(HCC)had lower overall survival rates.Patients with a high B/A ratio exhibited a lower overall survival than those with a low B/A rate in the overall cohort and the subgroups of patients with HCC or not,early Child-Pugh grade,low albumin-bilirubin grade,and model for end-stage liver disease score≥10(log-rank test,P<0.001 for all).CONCLUSION The B/A ratio can serve as an effective prognostic indicator for overall survival in patients with hepatitis B virusrelated cirrhosis following splenectomy,and a higher B/A ratio may suggest a poorer prognosis.
基金Supported by Zhejiang Provincial Natural Science Foundation of China,No.LTGY24H160006Jiaxing Medical Key Discipline,No.2023-ZC-015.
文摘BACKGROUND Serum carcinoembryonic antigen(CEA)levels and magnetic resonance imaging(MRI)findings are widely used for the diagnosis and treatment of rectal cancer;however,research investigating their correlation remains limited.AIM To investigate the correlation between baseline MRI features and serum CEA levels in patients diagnosed with primary rectal cancer.METHODS Eighty patients(age:42-78 years)diagnosed with primary rectal cancer were enrolled.Baseline MRI examinations were performed to evaluate tumor size,T stage,circumferential resection margin status,extramural vascular invasion(EMVI),and lymph node metastasis.Serum CEA levels were concurrently measured.Statistical methods were used to analyze correlations.RESULTS Tumor size,T stage,EMVI,and lymph node metastasis were significantly correlated with serum CEA levels(P<0.05).Multivariate analysis identified T stage and lymph node metastasis as independent factors influencing serum CEA levels.CONCLUSION This study confirmed the correlation between baseline MRI features and serum CEA levels in patients with primary rectal cancer,highlighting their potential utility for precise diagnosis,staging,and prognostic evaluation.
