Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6...Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6(IL-6)levels,which contribute to atrial remodeling and the progression of AF.This review summarizes the mechanisms by which IL-6 promotes AF through inflammatory pathways,atrial fibrosis,electrical remodeling,and calcium mishandling.Experimental models have demonstrated that IL-6 neutralization reduces the incidence of AF,highlighting its potential as a therapeutic target.Future studies should focus on IL-6 blockade strategies to manage AF,aiming to improve patient outcomes.展开更多
Objective This study aimed to analyse the trend of the mental disorder spectrum in children and adolescents from 2014 to 2022 in one city in Central China and to provide actionable recommendations for the prevention a...Objective This study aimed to analyse the trend of the mental disorder spectrum in children and adolescents from 2014 to 2022 in one city in Central China and to provide actionable recommendations for the prevention and management of mental disorders.Methods In this hospital-based retrospective study,we utilized child and adolescent medical records data from the Wuhan Mental Health Center from January 2014 to December 2022 and examined the top 5 mental disorders(schizophrenia,depressive episode,bipolar disorder,pervasive developmental disorder,and unspecified mood disorder)that accounted for the overall proportion of patients admitted.The rank and proportion of these mental disorders,demographic characteristics and disease indicators were analysed.Results There was a significant upwards trend in the number of children and adolescents diagnosed with mental disorders over the past 9 years,with a sharp decline in 2020 due to the COVID-19 pandemic,followed by a rebound in 2021 and a sustained level above prepandemic figures by 2022.The average age of hospitalization decreased significantly from 20.7 to 16.2 years,with a marked increase in the 12-17-year-old age group.The proportion of female hospitalizations increased from 39.2%to 55.2%,with a corresponding decrease in male hospitalizations.There was a notable decrease in the proportion of schizophrenia cases and an ascent of depressive episode to the most prevalent position.Conclusion This study emphasizes the critical need for targeted interventions and resources for severe mental disorders in children and adolescents and the importance of early detection and management of mental disorders to mitigate long-term effects on well-being and development.展开更多
Background and Objective Electromagnetic navigation technology has demonstrated significant potential in enhancing the accuracy and safety of neurosurgical procedures.However,traditional electromagnetic navigation sys...Background and Objective Electromagnetic navigation technology has demonstrated significant potential in enhancing the accuracy and safety of neurosurgical procedures.However,traditional electromagnetic navigation systems face challenges such as high equipment costs,complex operation,bulky size,and insufficient anti-interference performance.To address these limitations,our study developed and validated a novel portable electromagnetic neuronavigation system designed to improve the precision,accessibility,and clinical applicability of electromagnetic navigation technology in cranial surgery.Methods The software and hardware architecture of a portable neural magnetic navigation system was designed.The key technologies of the system were analysed,including electromagnetic positioning algorithms,miniaturized sensor design,optimization of electromagnetic positioning and navigation algorithms,anti-interference signal processing methods,and fast three-dimensional reconstruction algorithms.A prototype was developed,and its accuracy was tested.Finally,a preliminary clinical application evaluation was conducted.Results This study successfully developed a comprehensive portable electromagnetic neuronavigation system capable of achieving preoperative planning,intraoperative real-time positioning and navigation,and postoperative evaluation of navigation outcomes.Through rigorous collaborative testing of the system’s software and hardware,the accuracy of electromagnetic neuronavigation has been validated to meet clinical requirements.Conclusions This study developed a portable neuroelectromagnetic navigation system and validated its effectiveness and safety through rigorous model testing and preliminary clinical applications.The system is characterized by its compact size,high precision,excellent portability,and user-friendly operation,making it highly valuable for promoting navigation technology and advancing the precision and minimally invasive nature of neurosurgical procedures.展开更多
Erratum to:J Huazhong Univ Sci Technol[Med Sci]36(4):548–553,2016 https://doi.org/10.1007/s11596-016-1623-6 In the originally published article(https://doi.org/10.1007/s11596-016-1623-6),the immunofluorescence images...Erratum to:J Huazhong Univ Sci Technol[Med Sci]36(4):548–553,2016 https://doi.org/10.1007/s11596-016-1623-6 In the originally published article(https://doi.org/10.1007/s11596-016-1623-6),the immunofluorescence images in shRNA group in Fig.3 were accidentally used rather than the final,formal experiments.To retain consistency,the entire Fig.3 is replaced here with original images of the experiments.The authors declare that this correction will not affect the conclusion of the study.展开更多
Objective Atrial natriuretic peptide(ANP)and Zn^(2+)have been shown to confer cardioprotection against ischemia/reperfu-sion(I/R)injury.Zn^(2+)alleviates myocardial hypertrophy and pulmonary hypertension by regulating...Objective Atrial natriuretic peptide(ANP)and Zn^(2+)have been shown to confer cardioprotection against ischemia/reperfu-sion(I/R)injury.Zn^(2+)alleviates myocardial hypertrophy and pulmonary hypertension by regulating ANP expression,but its precise role in ANP-mediated cardioprotection remains unclear.This study aimed to investigate whether ANP protects the heart during reperfusion by modulating Zn^(2+)levels and to explore the underlying mechanisms involved.Methods In this study,we utilized an isolated reperfused heart model in rats,as well as wild-type(WT)and ANP knockout(ANP^(-/-))mouse models,for in vivo I/R experiments.For clinical investigations,plasma samples were collected from 216 patients with ischemia-related diseases.Evans blue and TTC staining,radioimmunoassay,ICP-OES,echocardiography,Hydro-Cy3-mediated ROS detection,and Western blotting were employed to evaluate the effect of ANP on Zn^(2+)homeostasis.Results Plasma ANP levels were significantly elevated in patients with ST-elevation myocardial infarction(STEMI),non-ST-elevation myocardial infarction(NSTEMI),and heart failure(HF).ANP secretion increased during reperfusion,rather than infarction,both ex vivo and in vivo,promoting Zn^(2+)accumulation in reperfused tissue.ANP and Zn^(2+)protected mito-chondria and reduced infarct size;these effects were reversed by the Zn^(2+)chelator TPEN.In WT and ANP^(-/-)mice,EF%and FS%decreased after reperfusion,with ANP^(-/-)mice exhibiting significantly worse cardiac function.ANP pretreatment alone improved cardiac function,but combined pretreatment with ANP and TPEN decreased EF%and FS%while increas-ing LVID.Reperfusion increased ROS levels in both WT and ANP^(-/-)hearts,which were reduced by ANP pretreatment.I/R injury elevated Zn^(2+)transporter 8(ZnT8)expression,an effect that was counteracted by ANP,although this effect was reversed by TPEN.Hypoxia-inducible factor 1-alpha(HIF-1α)expression was elevated in I/R rats and ANP^(-/-)mice,and it was inhibited by both Zn^(2+)and ANP pretreatment.However,the HIF-1αinhibitor 2-Me did not reverse the effect of ANP on ZnT8 expression.Additionally,ANP increased PI3K expression in both WT and ANP^(-/-)I/R mice,but this effect was blocked by the PI3K inhibitor LY294002.Conclusions ANP modulates Zn^(2+)homeostasis during reperfusion injury by downregulating ZnT8 through the PI3K signal-ling pathway,thereby reducing myocardial I/R injury.展开更多
Objective This study aimed to investigate the neuroprotective effects of cholecalciferol cholesterol emulsion(CCE),a vitamin D(VD)precursor,in a murine model of acute cerebral infarction(ACI)and to elucidate the role ...Objective This study aimed to investigate the neuroprotective effects of cholecalciferol cholesterol emulsion(CCE),a vitamin D(VD)precursor,in a murine model of acute cerebral infarction(ACI)and to elucidate the role of the Nrf2 signaling pathway in mediating these effects.Methods Forty C57BL/6J mice(male and female)were divided into five groups(n=10 per group):control,control+CCE,ACI,ACI+CCE,and ACI+CCE+ML385(an Nrf2 inhibitor).ACI was induced by middle cerebral artery occlusion(MCAO).CCE was administered for three weeks prior to ACI induction,and ML385 was administered intravenously to inhibit Nrf2.Neurological function,brain edema,and infarct size,as well as inflammatory and apoptotic marker levels,were assessed post-ACI.Statistical analyses were conducted via one-way ANOVA and Student's t test,with P<0.05 considered significant.Results Compared to ACI group,CCE significantly reduced neurological deficits,brain edema,and infarct size(P<0.01).The ACI+CCE group presented improved short-term memory retention,as evidenced by shorter avoidance latency in shuttle avoidance tests(P<0.01).CCE administration attenuated the expression of inflammatory markers(IL-6,MIF,Lp-PLA2)while increasing IL-10 levels(P<0.001).Furthermore,CCE increased Nrf2 and HO-1 expression and reduced apoptosis by decreasing the Bax/Bcl-2 ratio in brain tissue(P<0.001).ML385 abolished these neuroprotective effects,confirming the role of the Nrf2 pathway in mediating the benefits of VD.Conclusion VD,via VD receptor-mediated activation of the Nrf2/HO-1 pathway,reduces inflammation,apoptosis,and neurological damage following ACI.These findings support the therapeutic potential of VD in the treatment of ischemic stroke and highlight the importance of Nrf2 in mediating these effects.展开更多
Objective The study aimed to develop machine learning(ML)models to predict the mortality of patients with acute gastro-intestinal bleeding(AGIB)in the intensive care unit(ICU)and compared their prognostic performance ...Objective The study aimed to develop machine learning(ML)models to predict the mortality of patients with acute gastro-intestinal bleeding(AGIB)in the intensive care unit(ICU)and compared their prognostic performance with that of Acute Physiology and Chronic Health EvaluationⅡ(APACHE-Ⅱ)score.Methods A total of 961 AGIB patients admitted to the ICU of Renmin Hospital of Wuhan University from January 2020 to December 2023 were enrolled.Patients were randomly divided into the training cohort(n=768)and the validation cohort(n=193).Clinical data were collected within the first 24 h of ICU admission.ML models were constructed using Python V.3.7 package,employing 3 different algorithms:XGBoost,Random Forest(RF)and Gradient Boosting Decision Tree(GBDT).The area under the receiver operating characteristic(ROC)curve(AUC)was used to evaluate the performance of different models.Results A total of 94 patients died with an overall mortality of 9.78%(11.32%in the training cohort and 8.96%in the vali-dation cohort).Among the 3 ML models,the GBDT algorithm demonstrated the highest predictive performance,achieving an AUC of 0.95(95%CI 0.90-0.99),while the AUCs of XGBoost and RF models were 0.89(95%CI 0.82-0.96)and 0.90(95%CI 0.84-0.96),respectively.In comparison,the APACHE-Ⅱmodel achieved an AUC of 0.74(95%CI 0.69-0.87),with a specificity of 70.97%(95%CI 64.07-77.01).When APACHE-Ⅱscore was incorporated into the GBDT algorithm,the ensemble model achieved an AUC of 0.98(95%CI 0.96-0.99)with a sensitivity of 85.71%and a specificity up to 95.15%.Conclusions The GBDT model serves as a reliable tool for accurately predicting the in-hospital mortality for AGIB patients.When integrated with the APACHE-Ⅱscore,the ensemble GBDT algorithm further enhances predictive accuracy and pro-vides valuable insights for prognostic evaluation.展开更多
Objective This study aimed to investigate the association between insulin resistance and the risk of cardiovascular disease.Methods A cross-sectional study including 2128 participants aged 40-79 years was conducted us...Objective This study aimed to investigate the association between insulin resistance and the risk of cardiovascular disease.Methods A cross-sectional study including 2128 participants aged 40-79 years was conducted using data from the National Health and Nutrition Examination Survey from 1999 to 2018.The quantitative insulin sensitivity check index(QUICKI)and homeostasis model assessment ofβ-cell function(HOMA-β)were used as independent variables.The 10-year risk of a first hard atherosclerotic cardiovascular event was used as the dependent variable,with other potential confounding factors considered.Multivariate linear regression models and smooth curve fitting were used to assess the associations between insulin resistance and 10-year risk.Results A total of 2128 patients,comprising 1191 men and 937 women,were included in our analysis.The regression analyses revealed a negative correlation between the QUICKI score and the 10-year risk of a first hard atherosclerotic car-diovascular event[β=-8.85,CI(-15.77,-1.93)]after adjusting for age,race,body mass index,systolic blood pressure,diastolic blood pressure,hypertension treatment,smoking,diabetes,and low-density lipoprotein cholesterol.Conversely,an increase in HOMA-βwas associated with 10-year risk[β=6.84,CI(0.45,13.23)].Gender-specific subgroup analysis indicated that the QUICKI had aβvalue of 0.077(0.046,0.108)for men and 0.080(0.061,0.094)for women.Conclusion This study demonstrated that increased insulin resistance is linked to an increased risk of cardiovascular disease.展开更多
Objective Tumour cells in a hypoxic state are more invasive,have stronger self-renewal capabilities,and are difficult to treat because of their ability to promote tumour recurrence and metastasis.The glycolysis inhibi...Objective Tumour cells in a hypoxic state are more invasive,have stronger self-renewal capabilities,and are difficult to treat because of their ability to promote tumour recurrence and metastasis.The glycolysis inhibitor 3-bromopyruvic acid(3-BrPA)can completely inactivate glycolytic enzymes at extremely low drug concentrations,thereby exerting a strong inhibitory effect on the glucose energy metabolism of tumor cells.Therefore,we tested the inhibitory effect of 3-BrPA on hepatocellular carcinoma cells(HepG2)in vitro;then,we used the VX2 liver cancer model to study the antitumour effect of 3-BrPA combined with interventional embolization on liver cancer.Methods In vitro,a CCK-8 assay was used to detect the inhibitory effect of different concentrations of 3-BrPA on HepG2 cells,and light microscopy confirmed that the HepG2 cells were completely dead.Western blotting was used to detect the expression of key proteins involved in apoptosis.A total of 30 New Zealand white rabbits were used to establish a liver cancer model and were randomly divided into 3 groups 2 weeks after tumor establishment:the control group was perfused with saline in the hepatic artery;the transcatheter arterial embolization(TAE)group was given TAE;and the experimental group was perfused with 3-BrPA combined with TAE.The tumor-bearing rabbits were killed one week after surgery.The tumor volume and tumor necrosis ratio were calculated via the histopathological examination.Results In vitro,the inhibitory effect of 3-BrPA on HepG2 cells increased with increasing concentration.3-BrPA(100μmol/L)could induce the necrosis of HepG2 cells.Stimulation with 50μmol/L 3-BrPA could activate the tumor cell apoptosis pathway.3-BrPA combined with TAE treatment could significantly inhibit tumor growth and cause more complete tumor necrosis.Conclusion 3-BrPA not only has antitumour effects in vitro but can also significantly improve antitumour effects in the hypoxic microenvironment after embolization in vivo.展开更多
Objective Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment.ELMO domain containing 2(ELMOD2)is a GTPase-activating protein that regulates a range of cell...Objective Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment.ELMO domain containing 2(ELMOD2)is a GTPase-activating protein that regulates a range of cellular biological processes.However,its specific role and prognostic value in tumorigenesis are still unknown.This study aimed to assess the prognostic relevance and signaling function of ELMOD2 in gliomas.Methods The Chinese Glioma Genome Atlas(CGGA)and The Cancer Genome Atlas(TCGA)databases were utilized to conduct a comprehensive analysis of the expression profile of ELMOD2 in gliomas,elucidating its associations with clinicopathological parameters and patient prognosis.Single-cell analysis was performed to characterize ELMOD2 expression across distinct glioma cell subpopulations.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and Gene Set Variation Analysis(GSVA)were employed to evaluate the potential biological functions of ELMOD2 in gliomagenesis.Specific small interfering RNAs(siRNAs)were used to knock down ELMOD2 in the glioma cell lines U251 and A172 to assess their cellular behaviors and examine the levels of multiple key signaling molecules associated with the occurrence of gliomas.Results ELMOD2 was overexpressed in gliomas,and this upregulation was correlated with tumor grade,isocitrate dehydrogenase mutation,and 1p/19q codeletion status.Notably,ELMOD2 expression was elevated in classical and mesenchymal subtypes,and single-cell resolution analysis revealed predominant enrichment within malignant cells.Functionally,ELMOD2 regulated cell cycle progression,and its overexpression was related to independent adverse outcomes.In vitro experiments revealed that ELMOD2 was located in the cytoplasm and nucleoplasm.Furthermore,ELMOD2 knockdown reduced proliferation,migration,and invasion and increased apoptosis in U251 and A172 cell lines.Finally,ELMOD2 knockdown significantly decreased p-Erk1/2.Conclusions ELMOD2 expression in glioma is positively correlated with tumorigenesis and is a crucial independent prognostic marker.Thus,ELMOD2 is a promising biomarker and therapeutic target for glioma treatment.展开更多
Objective The lack of clarity regarding the application performance of a hybrid operating room(HOR)and the uncertainty of surgical scheduling often lead to its inefficient application.This study aimed to review the cl...Objective The lack of clarity regarding the application performance of a hybrid operating room(HOR)and the uncertainty of surgical scheduling often lead to its inefficient application.This study aimed to review the clinical application of our neurosurgical HOR and propose a scale to score cases clearly.Methods We reviewed the operating procedures and duration of stay in 1865 HOR cases.The actual procedures of each case were summarized into 5 application types,and numerical assignment was used to distinguish the dependence of each type on our HOR:surgical procedures combined with interventional procedures(4 points,the highest dependence),surgical procedures combined with imaging procedures(3 points),interventional procedures(2 points),imaging procedures(1 point),and surgical procedures(0 points,the lowest dependence).Results A novel scale that could score 1865 cases into those 5 grades was developed.The percentages by grade were as follows:4 points,4.24%;3 points,4.88%;2 points,20.75%;1 point,69.38%;and 0 points,0.75%.The cumulative usage time was 4241.9 h,the duration of which was as follows:4 points,16.17%;3 points,15.50%;2 points,31.32%;1 point,35.62%;and 0 points,1.39%.Conclusions The HOR serves as a multifunctional room to treat neurosurgical diseases.The scale helps to quickly prioritize cases that rely more on HOR,providing guidelines for surgical scheduling.Although our HOR is unsuitable for emergency cases,it clearly shows the application performance of our HOR to provide a reference for promoting its efficient application.展开更多
To the Editor,We have read the article by Gener-Ricos et al.titled"NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage",published in Cancer[1].This retrospective,cr...To the Editor,We have read the article by Gener-Ricos et al.titled"NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage",published in Cancer[1].This retrospective,cross-sectional pilot study provides valuable insights into the clinicopathological features and treatment outcomes of patients with NPM1-mutated myeloid neoplasms(MNs)with less than 20%bone marrow blasts[1].展开更多
Objective and Background Early and accurate diagnosis of spinal infections,including spinal tuberculosis,is pivotal for effective treatment but remains challenging.This study aims to assess the diagnostic yield of met...Objective and Background Early and accurate diagnosis of spinal infections,including spinal tuberculosis,is pivotal for effective treatment but remains challenging.This study aims to assess the diagnostic yield of metagenomic next-generation sequencing(mNGS)compared with that of conventional microbiological tests(CMTs)in identifying pathogens associated with spinal pathologies,with a special focus on infections leading to surgical interventions.Methods We enrolled 85 patients who underwent spinal surgery,comprising 63 patients with clinically diagnosed spinal infections,including patients with spinal tuberculosis,and 22 patients with noninfectious spinal conditions.The procedures involved irrigation and debridement for persistent wound drainage,with subsequent DNA extraction from plasma and joint fluid for mNGS and CMT analysis.Results Significantly increased C-reactive protein(CRP)levels were observed in patients with infections.The mNGS approach showed greater diagnostic sensitivity(92.06%)for detecting pathogens,including Mycobacterium tuberculosis,than did CMTs(36.51%).Despite its low specificity,mNGS had considerable negative predictive value(70.59%),underscoring its utility in ruling out infections.Conclusions The mNGS offers superior sensitivity over CMTs in the diagnosis of a variety of spinal infections,notably spinal tuberculosis.This study highlights the potential of mNGS in enhancing the diagnosis of complex spinal infections,thereby informing targeted treatment strategies.展开更多
Objective This study aims to investigate the exosome-derived metabolomics profiles in systemic lupus erythematosus(SLE),identify differential metabolites,and analyze their potential as diagnostic markers for SLE and l...Objective This study aims to investigate the exosome-derived metabolomics profiles in systemic lupus erythematosus(SLE),identify differential metabolites,and analyze their potential as diagnostic markers for SLE and lupus nephritis(LN).Methods Totally,91 participants were enrolled between February 2023 and January 2024 including 58 SLE patients[30 with nonrenal-SLE and 28 with Lupus nephritis(LN)]and 33 healthy controls(HC).Ultracentrifugation was used to isolate serum exosomes,which were analyzed for their metabolic profiles using liquid chromatography–tandem mass spectrometry(LC–MS/MS).Endogenous metabolites were identified via public metabolite databases.Random Forest,Lasso regression and Support Vector Machine Recursive Feature Elimination(SVM-RFE)algorithms were employed to screen key metabolites,and a prediction model was constructed for SLE diagnosis and LN discrimination.ROC curves were constructed to determine the potential of these differential exosome-derived metabolites for the diagnosis of SLE.Furthermore,Spearman’s correlation was employed to evaluate the potential links between exosome-derived metabolites and the clinical parameters which reflect disease progression.Results A total of 586 endogenous serum exosome-derived metabolites showed differential expression,with 225 exosome-derived metabolites significantly upregulated,88 downregulated and 273 exhibiting no notable changes in the HC and SLE groups.Machine learning algorithms revealed three differential metabolites:Pro-Asn-Gln-Met-Ser,C24:1 sphingolipid,and protoporphyrin IX,which exhibited AUC values of 0.998,0.992 and 0.969 respectively,for distinguishing between the SLE and HC groups,with a combined AUC of 1.0.In distinguishing between the LN and SLE groups,the AUC values for these metabolites were 0.920,0.893 and 0.865,respectively,with a combined AUC of 0.931,demonstrating excellent diagnostic performance.Spearman correlation analysis revealed that Pro-Asn-Gln-Met-Ser and protoporphyrin IX were positively correlated with the SLE Disease Activity Index(SLEDAI)scores,urinary protein/creatinine ratio(ACR)and urinary protein levels,while C24:1 sphingolipid exhibited a negative correlation.Conclusions This study provides the first comprehensive characterization of the exosome-derived metabolites in SLE and established a promising prediction model for SLE and LN discrimination.The correlation between exosome-derived metabolites and key clinical parameters strongly indicated their potential role in SLE pathological progression.展开更多
Objective Helicobacter pylori(HP)infection is associated with non-alcoholic fatty liver disease(NAFLD)and insulin resistance;however,the correlation between HP eradication and NAFLD remains controversial.This systemat...Objective Helicobacter pylori(HP)infection is associated with non-alcoholic fatty liver disease(NAFLD)and insulin resistance;however,the correlation between HP eradication and NAFLD remains controversial.This systematic review and meta-analysis examined the effect of HP treatment on clinical and laboratory parameters in NAFLD patients.Methods We conducted a literature search of the PubMed,Embase,Scopus,and Web of Science databases through Septem-ber 2023 for randomized controlled trials(RCTs)examining the effect of HP treatment on NAFLD patients versus lifestyle changes alone.The primary outcome was the change in steatosis parameters.The secondary endpoints were changes in anthropometric parameters,inflammatory markers(TNF-α),and metabolic parameters(fasting blood glucose,homeostasis model assessment of insulin resistance,AST/ALT,and lipid profile).The random effects model was used to calculate the standardized mean difference(SMD)with associated 95%confidence intervals(CIs)for our desired outcome.Results Four RCTs met our inclusion criteria.A total of 453 patients were included(mean age 42.8 years,58.5%males),228(50.3%)of whom were in the HP eradication group and 225(49.7%)of whom were in the lifestyle modification group.Compared with lifestyle modification alone,HP eradication had a significant effect on reducing liver steatosis and TNF-αlevels(SMD:-0.9;95%CI-14.67,-3.82,I^(2)=0%and SMD:-6.3;95%CI-9.04,-3.56,I^(2)=0%,respectively).No sig-nificant effect on other metabolic parameters was found.Conclusions HP eradication significantly reduced liver steatosis and TNF-αlevels in NAFLD patients.However,HP eradi-cation did not significantly affect other metabolic indices compared to lifestyle changes alone.展开更多
Ovarian cancer(OC),a highly lethal gynaecological malignancy,is often diagnosed at advanced stages,resulting in a poor prognosis.Sialylation,an important form of glycosylation,significantly contributes to the progress...Ovarian cancer(OC),a highly lethal gynaecological malignancy,is often diagnosed at advanced stages,resulting in a poor prognosis.Sialylation,an important form of glycosylation,significantly contributes to the progression of various solid tumours,including OC.Aberrant sialylation promotes tumour progression and metastasis by altering the structure and function of glycoproteins.Although its role in several solid tumours is well documented,the role of abnormal sialylation in OC and its potential as a therapeutic target remain poorly understood.This review highlights sialylation as a key regulator of the progression,metastasis,and drug resistance of OC.A deeper understanding of altered sialylation can contribute to the identification of novel therapeutic strategies for OC.展开更多
Jian-guo Chen is currently Professor and Chair of the Department of Pharmacology at Tongji Medical College,Huazhong University of Science and Technology(HUST),China.He received his PhD in Physiology from the Universit...Jian-guo Chen is currently Professor and Chair of the Department of Pharmacology at Tongji Medical College,Huazhong University of Science and Technology(HUST),China.He received his PhD in Physiology from the University of Heidelberg(Germany,1996-1998),following research training in molecular signaling at the University of Kaiserslautern(Germany,1995-1996),and completed postdoctoral studies on ion channel and synaptic plasticity at the University of Iowa College of Medicine(USA,1998-2001).展开更多
Background and Objective Inflammation plays a pivotal role in the progression of coronary artery disease(CAD).High-sensitivity C-reactive protein(hsCRP)serves as a well-established biomarker for assessing cardiovascul...Background and Objective Inflammation plays a pivotal role in the progression of coronary artery disease(CAD).High-sensitivity C-reactive protein(hsCRP)serves as a well-established biomarker for assessing cardiovascular inflammation risk.However,the specific intestinal microbiota alteration contributing to increased inflammation remains unclear.Therefore,the present study investigated the correlation between the intestinal microbiota and inflammation in patients with unstable angina(UA).Methods A cohort of 92 patients with UA was recruited for this study.The plasma hsCRP level was measured via a CardioPhase hsCRP assay,fecal samples were collected after admission,and 16S rRNA sequencing was conducted to identify the fecal microbial profile.The participants were classified into two groups according to the median hsCRP level(1.11 mg/L).The composition of the fecal microbiota was compared between patients with hsCRP≥1.11 mg/L and those with hsCRP<1.11 mg/L.Additionally,the correlations between the fecal microbiota and clinical characteristics were analyzed.Results A notable reduction in the relative abundance of Akkermansia was observed in patients with hsCRP≥1.11 mg/L,whereas the diversity of the fecal microbiota was not significantly different between patients with hsCRP≥1.11 mg/L and those with hsCRP<1.11 mg/L.Furthermore,the abundance of Akkermansia was negatively correlated with hsCRP levels.Conclusion This study suggested a significant association between decreased levels of Akkermansia and inflammatory risk in patients with UA.These findings underscore the potential role of the intestinal microbiota in contributing to inflammation in UA patients.Further work is needed on the mechanism by which the microbiota contributes to inflammatory risk.展开更多
Objective To investigate the combined effects of thymidine phosphorylase(TYMP)and sine oculis homeobox homologue 1(Six1)on the tumor microenvironment and their role in promoting metastasis in gastric cancer(GC).Method...Objective To investigate the combined effects of thymidine phosphorylase(TYMP)and sine oculis homeobox homologue 1(Six1)on the tumor microenvironment and their role in promoting metastasis in gastric cancer(GC).Methods A total of 674 GC patients who underwent surgical resection were enrolled.Correlations between TYMP/Six1 expression and the clinicopathological characteristics and overall survival of patients were analysed.The expression of TYMP,Six1 and vascular endothelial growth factor C(VEGFc)was quantified via immunohistochemistry and quantitative real-time polymerase chain reaction.Cell transfection,wound-healing assays and bioinformatics analyses were used to explore the potential underlying mechanisms involved.Results Compared with the other groups,the Six1+/TYMP+patients exhibited poor differentiation,advanced tumor stage,a higher rate of lymphatic vessel invasion and shorter survival.Additionally,the protein expression of TYMP and Six1 was positively correlated with the VEGFc level.A significant increase in VEGFc expression was observed in cells transfected with TYMP,Six1,and TYMP/Six1 vectors.The results of the wound-healing assay indicated that the synergistic effect of TYMP and Six1 enhanced the migratory ability of GC cells.Furthermore,bioinformatics analysis revealed that TYMP and Six1 were positively correlated with immunosuppressive immune cell subsets and elevated the expression of inhibitory immune checkpoints in GC.Conclusions The combination of TYMP and Six1 is a good predictive and prognostic biomarker for GC.This combination enhances the expression of VEGFc,facilitates the invasion of GC cells,and may be linked to inhibitory immune cells and the tumor immune microenvironment.展开更多
Objective Hepatocellular carcinoma(HCC),a lethal cancer with high global mortality,may be targeted through ferroptosis,an iron-dependent form of cell death.Despite its potential,the prognostic value of ferroptosis in ...Objective Hepatocellular carcinoma(HCC),a lethal cancer with high global mortality,may be targeted through ferroptosis,an iron-dependent form of cell death.Despite its potential,the prognostic value of ferroptosis in HCC is underexplored.Methods Our study leveraged single-cell and bulk sequencing datasets to identify ferroptosis-related genes and developed a prognostic model via Cox and LASSO regression analyses.Survival and mutation analyses led to the creation of a nomo-gram for predicting patient prognosis.Furthermore,we investigated the role of GRINA,a ferroptosis-related gene,through functional assays,including cell proliferation,colony formation,and metastatic potential analyses.We also assessed mito-chondrial abnormalities,intracellular iron,and ROS levels in GRINA-knockdown cells.Results The developed ferroptosis-related model classified HCC patients into risk groups,revealing notable survival dispari-ties.High-risk patients presented increased immune checkpoint gene expression.The nomogram revealed robust prognostic accuracy.Additionally,we found that GRINA suppression reduced HCC cell proliferation,colony formation,and metastatic potential.Cells with GRINA knockdown presented mitochondrial abnormalities and increased intracellular iron and ROS levels.Conclusions By analysing multiomics sequencing data,we established a connection between ferroptosis-related risk groups and the tumor immune microenvironment.These findings provide novel insights into the role of ferroptosis in HCC and suggest that GRINA inhibition is a potential therapeutic strategy,leading to mitochondrial damage and the induction of fer-roptosis in HCC cell lines.展开更多
基金supported by the National Natural Science Foundation of China(No.82170326 and No.82470328 to Y.D.,No.82100339 to Q.D.).
文摘Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6(IL-6)levels,which contribute to atrial remodeling and the progression of AF.This review summarizes the mechanisms by which IL-6 promotes AF through inflammatory pathways,atrial fibrosis,electrical remodeling,and calcium mishandling.Experimental models have demonstrated that IL-6 neutralization reduces the incidence of AF,highlighting its potential as a therapeutic target.Future studies should focus on IL-6 blockade strategies to manage AF,aiming to improve patient outcomes.
文摘Objective This study aimed to analyse the trend of the mental disorder spectrum in children and adolescents from 2014 to 2022 in one city in Central China and to provide actionable recommendations for the prevention and management of mental disorders.Methods In this hospital-based retrospective study,we utilized child and adolescent medical records data from the Wuhan Mental Health Center from January 2014 to December 2022 and examined the top 5 mental disorders(schizophrenia,depressive episode,bipolar disorder,pervasive developmental disorder,and unspecified mood disorder)that accounted for the overall proportion of patients admitted.The rank and proportion of these mental disorders,demographic characteristics and disease indicators were analysed.Results There was a significant upwards trend in the number of children and adolescents diagnosed with mental disorders over the past 9 years,with a sharp decline in 2020 due to the COVID-19 pandemic,followed by a rebound in 2021 and a sustained level above prepandemic figures by 2022.The average age of hospitalization decreased significantly from 20.7 to 16.2 years,with a marked increase in the 12-17-year-old age group.The proportion of female hospitalizations increased from 39.2%to 55.2%,with a corresponding decrease in male hospitalizations.There was a notable decrease in the proportion of schizophrenia cases and an ascent of depressive episode to the most prevalent position.Conclusion This study emphasizes the critical need for targeted interventions and resources for severe mental disorders in children and adolescents and the importance of early detection and management of mental disorders to mitigate long-term effects on well-being and development.
基金funded by National Natural Science Foundation of China(No.82272134)Innovative Research Group Project of the National Natural Science Foundation of China(No.82272134,Xiao-lei Chen).
文摘Background and Objective Electromagnetic navigation technology has demonstrated significant potential in enhancing the accuracy and safety of neurosurgical procedures.However,traditional electromagnetic navigation systems face challenges such as high equipment costs,complex operation,bulky size,and insufficient anti-interference performance.To address these limitations,our study developed and validated a novel portable electromagnetic neuronavigation system designed to improve the precision,accessibility,and clinical applicability of electromagnetic navigation technology in cranial surgery.Methods The software and hardware architecture of a portable neural magnetic navigation system was designed.The key technologies of the system were analysed,including electromagnetic positioning algorithms,miniaturized sensor design,optimization of electromagnetic positioning and navigation algorithms,anti-interference signal processing methods,and fast three-dimensional reconstruction algorithms.A prototype was developed,and its accuracy was tested.Finally,a preliminary clinical application evaluation was conducted.Results This study successfully developed a comprehensive portable electromagnetic neuronavigation system capable of achieving preoperative planning,intraoperative real-time positioning and navigation,and postoperative evaluation of navigation outcomes.Through rigorous collaborative testing of the system’s software and hardware,the accuracy of electromagnetic neuronavigation has been validated to meet clinical requirements.Conclusions This study developed a portable neuroelectromagnetic navigation system and validated its effectiveness and safety through rigorous model testing and preliminary clinical applications.The system is characterized by its compact size,high precision,excellent portability,and user-friendly operation,making it highly valuable for promoting navigation technology and advancing the precision and minimally invasive nature of neurosurgical procedures.
文摘Erratum to:J Huazhong Univ Sci Technol[Med Sci]36(4):548–553,2016 https://doi.org/10.1007/s11596-016-1623-6 In the originally published article(https://doi.org/10.1007/s11596-016-1623-6),the immunofluorescence images in shRNA group in Fig.3 were accidentally used rather than the final,formal experiments.To retain consistency,the entire Fig.3 is replaced here with original images of the experiments.The authors declare that this correction will not affect the conclusion of the study.
基金supported by the National Natural Science Foundation of China(NSFC)(No.82360065 and No.81760047).
文摘Objective Atrial natriuretic peptide(ANP)and Zn^(2+)have been shown to confer cardioprotection against ischemia/reperfu-sion(I/R)injury.Zn^(2+)alleviates myocardial hypertrophy and pulmonary hypertension by regulating ANP expression,but its precise role in ANP-mediated cardioprotection remains unclear.This study aimed to investigate whether ANP protects the heart during reperfusion by modulating Zn^(2+)levels and to explore the underlying mechanisms involved.Methods In this study,we utilized an isolated reperfused heart model in rats,as well as wild-type(WT)and ANP knockout(ANP^(-/-))mouse models,for in vivo I/R experiments.For clinical investigations,plasma samples were collected from 216 patients with ischemia-related diseases.Evans blue and TTC staining,radioimmunoassay,ICP-OES,echocardiography,Hydro-Cy3-mediated ROS detection,and Western blotting were employed to evaluate the effect of ANP on Zn^(2+)homeostasis.Results Plasma ANP levels were significantly elevated in patients with ST-elevation myocardial infarction(STEMI),non-ST-elevation myocardial infarction(NSTEMI),and heart failure(HF).ANP secretion increased during reperfusion,rather than infarction,both ex vivo and in vivo,promoting Zn^(2+)accumulation in reperfused tissue.ANP and Zn^(2+)protected mito-chondria and reduced infarct size;these effects were reversed by the Zn^(2+)chelator TPEN.In WT and ANP^(-/-)mice,EF%and FS%decreased after reperfusion,with ANP^(-/-)mice exhibiting significantly worse cardiac function.ANP pretreatment alone improved cardiac function,but combined pretreatment with ANP and TPEN decreased EF%and FS%while increas-ing LVID.Reperfusion increased ROS levels in both WT and ANP^(-/-)hearts,which were reduced by ANP pretreatment.I/R injury elevated Zn^(2+)transporter 8(ZnT8)expression,an effect that was counteracted by ANP,although this effect was reversed by TPEN.Hypoxia-inducible factor 1-alpha(HIF-1α)expression was elevated in I/R rats and ANP^(-/-)mice,and it was inhibited by both Zn^(2+)and ANP pretreatment.However,the HIF-1αinhibitor 2-Me did not reverse the effect of ANP on ZnT8 expression.Additionally,ANP increased PI3K expression in both WT and ANP^(-/-)I/R mice,but this effect was blocked by the PI3K inhibitor LY294002.Conclusions ANP modulates Zn^(2+)homeostasis during reperfusion injury by downregulating ZnT8 through the PI3K signal-ling pathway,thereby reducing myocardial I/R injury.
基金supported by the Medical Science Research Project Program of Hebei Province(20211722).
文摘Objective This study aimed to investigate the neuroprotective effects of cholecalciferol cholesterol emulsion(CCE),a vitamin D(VD)precursor,in a murine model of acute cerebral infarction(ACI)and to elucidate the role of the Nrf2 signaling pathway in mediating these effects.Methods Forty C57BL/6J mice(male and female)were divided into five groups(n=10 per group):control,control+CCE,ACI,ACI+CCE,and ACI+CCE+ML385(an Nrf2 inhibitor).ACI was induced by middle cerebral artery occlusion(MCAO).CCE was administered for three weeks prior to ACI induction,and ML385 was administered intravenously to inhibit Nrf2.Neurological function,brain edema,and infarct size,as well as inflammatory and apoptotic marker levels,were assessed post-ACI.Statistical analyses were conducted via one-way ANOVA and Student's t test,with P<0.05 considered significant.Results Compared to ACI group,CCE significantly reduced neurological deficits,brain edema,and infarct size(P<0.01).The ACI+CCE group presented improved short-term memory retention,as evidenced by shorter avoidance latency in shuttle avoidance tests(P<0.01).CCE administration attenuated the expression of inflammatory markers(IL-6,MIF,Lp-PLA2)while increasing IL-10 levels(P<0.001).Furthermore,CCE increased Nrf2 and HO-1 expression and reduced apoptosis by decreasing the Bax/Bcl-2 ratio in brain tissue(P<0.001).ML385 abolished these neuroprotective effects,confirming the role of the Nrf2 pathway in mediating the benefits of VD.Conclusion VD,via VD receptor-mediated activation of the Nrf2/HO-1 pathway,reduces inflammation,apoptosis,and neurological damage following ACI.These findings support the therapeutic potential of VD in the treatment of ischemic stroke and highlight the importance of Nrf2 in mediating these effects.
基金supported by the Cross Innovation Talent Project,Renmin Hospital of Wuhan University(No.JCRCYG-2022-005,No.JCRCZN-2022-017)the National Natural Science Foundation of China(No.82302418)+1 种基金the Knowledge Innovation Program of Wuhan,Science and Technology Innovation of Wuhan(No.2023020201010165)The Key Project of Education Foundation,Guang Zhou 21st Century Education Foundation(No.2023HX0054).
文摘Objective The study aimed to develop machine learning(ML)models to predict the mortality of patients with acute gastro-intestinal bleeding(AGIB)in the intensive care unit(ICU)and compared their prognostic performance with that of Acute Physiology and Chronic Health EvaluationⅡ(APACHE-Ⅱ)score.Methods A total of 961 AGIB patients admitted to the ICU of Renmin Hospital of Wuhan University from January 2020 to December 2023 were enrolled.Patients were randomly divided into the training cohort(n=768)and the validation cohort(n=193).Clinical data were collected within the first 24 h of ICU admission.ML models were constructed using Python V.3.7 package,employing 3 different algorithms:XGBoost,Random Forest(RF)and Gradient Boosting Decision Tree(GBDT).The area under the receiver operating characteristic(ROC)curve(AUC)was used to evaluate the performance of different models.Results A total of 94 patients died with an overall mortality of 9.78%(11.32%in the training cohort and 8.96%in the vali-dation cohort).Among the 3 ML models,the GBDT algorithm demonstrated the highest predictive performance,achieving an AUC of 0.95(95%CI 0.90-0.99),while the AUCs of XGBoost and RF models were 0.89(95%CI 0.82-0.96)and 0.90(95%CI 0.84-0.96),respectively.In comparison,the APACHE-Ⅱmodel achieved an AUC of 0.74(95%CI 0.69-0.87),with a specificity of 70.97%(95%CI 64.07-77.01).When APACHE-Ⅱscore was incorporated into the GBDT algorithm,the ensemble model achieved an AUC of 0.98(95%CI 0.96-0.99)with a sensitivity of 85.71%and a specificity up to 95.15%.Conclusions The GBDT model serves as a reliable tool for accurately predicting the in-hospital mortality for AGIB patients.When integrated with the APACHE-Ⅱscore,the ensemble GBDT algorithm further enhances predictive accuracy and pro-vides valuable insights for prognostic evaluation.
基金supported by Hostital Capability Enhancement Project of Xiyuan Hospital,CACMS.(No.XYZX0405-25).
文摘Objective This study aimed to investigate the association between insulin resistance and the risk of cardiovascular disease.Methods A cross-sectional study including 2128 participants aged 40-79 years was conducted using data from the National Health and Nutrition Examination Survey from 1999 to 2018.The quantitative insulin sensitivity check index(QUICKI)and homeostasis model assessment ofβ-cell function(HOMA-β)were used as independent variables.The 10-year risk of a first hard atherosclerotic cardiovascular event was used as the dependent variable,with other potential confounding factors considered.Multivariate linear regression models and smooth curve fitting were used to assess the associations between insulin resistance and 10-year risk.Results A total of 2128 patients,comprising 1191 men and 937 women,were included in our analysis.The regression analyses revealed a negative correlation between the QUICKI score and the 10-year risk of a first hard atherosclerotic car-diovascular event[β=-8.85,CI(-15.77,-1.93)]after adjusting for age,race,body mass index,systolic blood pressure,diastolic blood pressure,hypertension treatment,smoking,diabetes,and low-density lipoprotein cholesterol.Conversely,an increase in HOMA-βwas associated with 10-year risk[β=6.84,CI(0.45,13.23)].Gender-specific subgroup analysis indicated that the QUICKI had aβvalue of 0.077(0.046,0.108)for men and 0.080(0.061,0.094)for women.Conclusion This study demonstrated that increased insulin resistance is linked to an increased risk of cardiovascular disease.
基金National Natural Science Foundation of China(No.82202281)for the funding support,and Yu-miao Wei for his review of the manuscript.
文摘Objective Tumour cells in a hypoxic state are more invasive,have stronger self-renewal capabilities,and are difficult to treat because of their ability to promote tumour recurrence and metastasis.The glycolysis inhibitor 3-bromopyruvic acid(3-BrPA)can completely inactivate glycolytic enzymes at extremely low drug concentrations,thereby exerting a strong inhibitory effect on the glucose energy metabolism of tumor cells.Therefore,we tested the inhibitory effect of 3-BrPA on hepatocellular carcinoma cells(HepG2)in vitro;then,we used the VX2 liver cancer model to study the antitumour effect of 3-BrPA combined with interventional embolization on liver cancer.Methods In vitro,a CCK-8 assay was used to detect the inhibitory effect of different concentrations of 3-BrPA on HepG2 cells,and light microscopy confirmed that the HepG2 cells were completely dead.Western blotting was used to detect the expression of key proteins involved in apoptosis.A total of 30 New Zealand white rabbits were used to establish a liver cancer model and were randomly divided into 3 groups 2 weeks after tumor establishment:the control group was perfused with saline in the hepatic artery;the transcatheter arterial embolization(TAE)group was given TAE;and the experimental group was perfused with 3-BrPA combined with TAE.The tumor-bearing rabbits were killed one week after surgery.The tumor volume and tumor necrosis ratio were calculated via the histopathological examination.Results In vitro,the inhibitory effect of 3-BrPA on HepG2 cells increased with increasing concentration.3-BrPA(100μmol/L)could induce the necrosis of HepG2 cells.Stimulation with 50μmol/L 3-BrPA could activate the tumor cell apoptosis pathway.3-BrPA combined with TAE treatment could significantly inhibit tumor growth and cause more complete tumor necrosis.Conclusion 3-BrPA not only has antitumour effects in vitro but can also significantly improve antitumour effects in the hypoxic microenvironment after embolization in vivo.
基金supported by grants from the Natural Science Foundation of Guangxi Province(Grant No:2022GXNSFAA035639 and 2023GXNSFBA026092)the National Natural Science Foundation of China(Grant No:81860445 and 82260554)the Innovation Project of Guangxi Graduate Education(Grant No:YCBZ2024118)。
文摘Objective Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment.ELMO domain containing 2(ELMOD2)is a GTPase-activating protein that regulates a range of cellular biological processes.However,its specific role and prognostic value in tumorigenesis are still unknown.This study aimed to assess the prognostic relevance and signaling function of ELMOD2 in gliomas.Methods The Chinese Glioma Genome Atlas(CGGA)and The Cancer Genome Atlas(TCGA)databases were utilized to conduct a comprehensive analysis of the expression profile of ELMOD2 in gliomas,elucidating its associations with clinicopathological parameters and patient prognosis.Single-cell analysis was performed to characterize ELMOD2 expression across distinct glioma cell subpopulations.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and Gene Set Variation Analysis(GSVA)were employed to evaluate the potential biological functions of ELMOD2 in gliomagenesis.Specific small interfering RNAs(siRNAs)were used to knock down ELMOD2 in the glioma cell lines U251 and A172 to assess their cellular behaviors and examine the levels of multiple key signaling molecules associated with the occurrence of gliomas.Results ELMOD2 was overexpressed in gliomas,and this upregulation was correlated with tumor grade,isocitrate dehydrogenase mutation,and 1p/19q codeletion status.Notably,ELMOD2 expression was elevated in classical and mesenchymal subtypes,and single-cell resolution analysis revealed predominant enrichment within malignant cells.Functionally,ELMOD2 regulated cell cycle progression,and its overexpression was related to independent adverse outcomes.In vitro experiments revealed that ELMOD2 was located in the cytoplasm and nucleoplasm.Furthermore,ELMOD2 knockdown reduced proliferation,migration,and invasion and increased apoptosis in U251 and A172 cell lines.Finally,ELMOD2 knockdown significantly decreased p-Erk1/2.Conclusions ELMOD2 expression in glioma is positively correlated with tumorigenesis and is a crucial independent prognostic marker.Thus,ELMOD2 is a promising biomarker and therapeutic target for glioma treatment.
基金supported by the Technology Innovation Special Major Project of Hubei Province(grant number 2022BCA003).
文摘Objective The lack of clarity regarding the application performance of a hybrid operating room(HOR)and the uncertainty of surgical scheduling often lead to its inefficient application.This study aimed to review the clinical application of our neurosurgical HOR and propose a scale to score cases clearly.Methods We reviewed the operating procedures and duration of stay in 1865 HOR cases.The actual procedures of each case were summarized into 5 application types,and numerical assignment was used to distinguish the dependence of each type on our HOR:surgical procedures combined with interventional procedures(4 points,the highest dependence),surgical procedures combined with imaging procedures(3 points),interventional procedures(2 points),imaging procedures(1 point),and surgical procedures(0 points,the lowest dependence).Results A novel scale that could score 1865 cases into those 5 grades was developed.The percentages by grade were as follows:4 points,4.24%;3 points,4.88%;2 points,20.75%;1 point,69.38%;and 0 points,0.75%.The cumulative usage time was 4241.9 h,the duration of which was as follows:4 points,16.17%;3 points,15.50%;2 points,31.32%;1 point,35.62%;and 0 points,1.39%.Conclusions The HOR serves as a multifunctional room to treat neurosurgical diseases.The scale helps to quickly prioritize cases that rely more on HOR,providing guidelines for surgical scheduling.Although our HOR is unsuitable for emergency cases,it clearly shows the application performance of our HOR to provide a reference for promoting its efficient application.
文摘To the Editor,We have read the article by Gener-Ricos et al.titled"NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage",published in Cancer[1].This retrospective,cross-sectional pilot study provides valuable insights into the clinicopathological features and treatment outcomes of patients with NPM1-mutated myeloid neoplasms(MNs)with less than 20%bone marrow blasts[1].
基金supported by the Hubei Provincial Natural Science Foundation of China(No.2023AFB646)Knowledge Innovation Program of Wuhan(No.2023020201010155)Educational Research Program of Huazhong University of Science and Technology(No.2022135).
文摘Objective and Background Early and accurate diagnosis of spinal infections,including spinal tuberculosis,is pivotal for effective treatment but remains challenging.This study aims to assess the diagnostic yield of metagenomic next-generation sequencing(mNGS)compared with that of conventional microbiological tests(CMTs)in identifying pathogens associated with spinal pathologies,with a special focus on infections leading to surgical interventions.Methods We enrolled 85 patients who underwent spinal surgery,comprising 63 patients with clinically diagnosed spinal infections,including patients with spinal tuberculosis,and 22 patients with noninfectious spinal conditions.The procedures involved irrigation and debridement for persistent wound drainage,with subsequent DNA extraction from plasma and joint fluid for mNGS and CMT analysis.Results Significantly increased C-reactive protein(CRP)levels were observed in patients with infections.The mNGS approach showed greater diagnostic sensitivity(92.06%)for detecting pathogens,including Mycobacterium tuberculosis,than did CMTs(36.51%).Despite its low specificity,mNGS had considerable negative predictive value(70.59%),underscoring its utility in ruling out infections.Conclusions The mNGS offers superior sensitivity over CMTs in the diagnosis of a variety of spinal infections,notably spinal tuberculosis.This study highlights the potential of mNGS in enhancing the diagnosis of complex spinal infections,thereby informing targeted treatment strategies.
基金funded by National Natural Science Foundation of China to Ping Yang with Grant number No.82202600by Nanjing Drum Tower Hospital to Ping Yang with Grant number No.2024-LCYJ-MS-11then to Shou-bin Zhan with Grant number No.2023-JCYJ-QP-25.
文摘Objective This study aims to investigate the exosome-derived metabolomics profiles in systemic lupus erythematosus(SLE),identify differential metabolites,and analyze their potential as diagnostic markers for SLE and lupus nephritis(LN).Methods Totally,91 participants were enrolled between February 2023 and January 2024 including 58 SLE patients[30 with nonrenal-SLE and 28 with Lupus nephritis(LN)]and 33 healthy controls(HC).Ultracentrifugation was used to isolate serum exosomes,which were analyzed for their metabolic profiles using liquid chromatography–tandem mass spectrometry(LC–MS/MS).Endogenous metabolites were identified via public metabolite databases.Random Forest,Lasso regression and Support Vector Machine Recursive Feature Elimination(SVM-RFE)algorithms were employed to screen key metabolites,and a prediction model was constructed for SLE diagnosis and LN discrimination.ROC curves were constructed to determine the potential of these differential exosome-derived metabolites for the diagnosis of SLE.Furthermore,Spearman’s correlation was employed to evaluate the potential links between exosome-derived metabolites and the clinical parameters which reflect disease progression.Results A total of 586 endogenous serum exosome-derived metabolites showed differential expression,with 225 exosome-derived metabolites significantly upregulated,88 downregulated and 273 exhibiting no notable changes in the HC and SLE groups.Machine learning algorithms revealed three differential metabolites:Pro-Asn-Gln-Met-Ser,C24:1 sphingolipid,and protoporphyrin IX,which exhibited AUC values of 0.998,0.992 and 0.969 respectively,for distinguishing between the SLE and HC groups,with a combined AUC of 1.0.In distinguishing between the LN and SLE groups,the AUC values for these metabolites were 0.920,0.893 and 0.865,respectively,with a combined AUC of 0.931,demonstrating excellent diagnostic performance.Spearman correlation analysis revealed that Pro-Asn-Gln-Met-Ser and protoporphyrin IX were positively correlated with the SLE Disease Activity Index(SLEDAI)scores,urinary protein/creatinine ratio(ACR)and urinary protein levels,while C24:1 sphingolipid exhibited a negative correlation.Conclusions This study provides the first comprehensive characterization of the exosome-derived metabolites in SLE and established a promising prediction model for SLE and LN discrimination.The correlation between exosome-derived metabolites and key clinical parameters strongly indicated their potential role in SLE pathological progression.
文摘Objective Helicobacter pylori(HP)infection is associated with non-alcoholic fatty liver disease(NAFLD)and insulin resistance;however,the correlation between HP eradication and NAFLD remains controversial.This systematic review and meta-analysis examined the effect of HP treatment on clinical and laboratory parameters in NAFLD patients.Methods We conducted a literature search of the PubMed,Embase,Scopus,and Web of Science databases through Septem-ber 2023 for randomized controlled trials(RCTs)examining the effect of HP treatment on NAFLD patients versus lifestyle changes alone.The primary outcome was the change in steatosis parameters.The secondary endpoints were changes in anthropometric parameters,inflammatory markers(TNF-α),and metabolic parameters(fasting blood glucose,homeostasis model assessment of insulin resistance,AST/ALT,and lipid profile).The random effects model was used to calculate the standardized mean difference(SMD)with associated 95%confidence intervals(CIs)for our desired outcome.Results Four RCTs met our inclusion criteria.A total of 453 patients were included(mean age 42.8 years,58.5%males),228(50.3%)of whom were in the HP eradication group and 225(49.7%)of whom were in the lifestyle modification group.Compared with lifestyle modification alone,HP eradication had a significant effect on reducing liver steatosis and TNF-αlevels(SMD:-0.9;95%CI-14.67,-3.82,I^(2)=0%and SMD:-6.3;95%CI-9.04,-3.56,I^(2)=0%,respectively).No sig-nificant effect on other metabolic parameters was found.Conclusions HP eradication significantly reduced liver steatosis and TNF-αlevels in NAFLD patients.However,HP eradi-cation did not significantly affect other metabolic indices compared to lifestyle changes alone.
基金supported by Hubei Provincial Natural Science Foundation of China(No.2023AFB670).
文摘Ovarian cancer(OC),a highly lethal gynaecological malignancy,is often diagnosed at advanced stages,resulting in a poor prognosis.Sialylation,an important form of glycosylation,significantly contributes to the progression of various solid tumours,including OC.Aberrant sialylation promotes tumour progression and metastasis by altering the structure and function of glycoproteins.Although its role in several solid tumours is well documented,the role of abnormal sialylation in OC and its potential as a therapeutic target remain poorly understood.This review highlights sialylation as a key regulator of the progression,metastasis,and drug resistance of OC.A deeper understanding of altered sialylation can contribute to the identification of novel therapeutic strategies for OC.
文摘Jian-guo Chen is currently Professor and Chair of the Department of Pharmacology at Tongji Medical College,Huazhong University of Science and Technology(HUST),China.He received his PhD in Physiology from the University of Heidelberg(Germany,1996-1998),following research training in molecular signaling at the University of Kaiserslautern(Germany,1995-1996),and completed postdoctoral studies on ion channel and synaptic plasticity at the University of Iowa College of Medicine(USA,1998-2001).
基金supported by the National Natural Science Foundation of China(No.82030016,No 82230011 and No.82200533).
文摘Background and Objective Inflammation plays a pivotal role in the progression of coronary artery disease(CAD).High-sensitivity C-reactive protein(hsCRP)serves as a well-established biomarker for assessing cardiovascular inflammation risk.However,the specific intestinal microbiota alteration contributing to increased inflammation remains unclear.Therefore,the present study investigated the correlation between the intestinal microbiota and inflammation in patients with unstable angina(UA).Methods A cohort of 92 patients with UA was recruited for this study.The plasma hsCRP level was measured via a CardioPhase hsCRP assay,fecal samples were collected after admission,and 16S rRNA sequencing was conducted to identify the fecal microbial profile.The participants were classified into two groups according to the median hsCRP level(1.11 mg/L).The composition of the fecal microbiota was compared between patients with hsCRP≥1.11 mg/L and those with hsCRP<1.11 mg/L.Additionally,the correlations between the fecal microbiota and clinical characteristics were analyzed.Results A notable reduction in the relative abundance of Akkermansia was observed in patients with hsCRP≥1.11 mg/L,whereas the diversity of the fecal microbiota was not significantly different between patients with hsCRP≥1.11 mg/L and those with hsCRP<1.11 mg/L.Furthermore,the abundance of Akkermansia was negatively correlated with hsCRP levels.Conclusion This study suggested a significant association between decreased levels of Akkermansia and inflammatory risk in patients with UA.These findings underscore the potential role of the intestinal microbiota in contributing to inflammation in UA patients.Further work is needed on the mechanism by which the microbiota contributes to inflammatory risk.
基金supported by the National Natural Science Foundation of China(No.81602104).
文摘Objective To investigate the combined effects of thymidine phosphorylase(TYMP)and sine oculis homeobox homologue 1(Six1)on the tumor microenvironment and their role in promoting metastasis in gastric cancer(GC).Methods A total of 674 GC patients who underwent surgical resection were enrolled.Correlations between TYMP/Six1 expression and the clinicopathological characteristics and overall survival of patients were analysed.The expression of TYMP,Six1 and vascular endothelial growth factor C(VEGFc)was quantified via immunohistochemistry and quantitative real-time polymerase chain reaction.Cell transfection,wound-healing assays and bioinformatics analyses were used to explore the potential underlying mechanisms involved.Results Compared with the other groups,the Six1+/TYMP+patients exhibited poor differentiation,advanced tumor stage,a higher rate of lymphatic vessel invasion and shorter survival.Additionally,the protein expression of TYMP and Six1 was positively correlated with the VEGFc level.A significant increase in VEGFc expression was observed in cells transfected with TYMP,Six1,and TYMP/Six1 vectors.The results of the wound-healing assay indicated that the synergistic effect of TYMP and Six1 enhanced the migratory ability of GC cells.Furthermore,bioinformatics analysis revealed that TYMP and Six1 were positively correlated with immunosuppressive immune cell subsets and elevated the expression of inhibitory immune checkpoints in GC.Conclusions The combination of TYMP and Six1 is a good predictive and prognostic biomarker for GC.This combination enhances the expression of VEGFc,facilitates the invasion of GC cells,and may be linked to inhibitory immune cells and the tumor immune microenvironment.
基金supported by the National Natural Science Foundation of China(No.82102512).
文摘Objective Hepatocellular carcinoma(HCC),a lethal cancer with high global mortality,may be targeted through ferroptosis,an iron-dependent form of cell death.Despite its potential,the prognostic value of ferroptosis in HCC is underexplored.Methods Our study leveraged single-cell and bulk sequencing datasets to identify ferroptosis-related genes and developed a prognostic model via Cox and LASSO regression analyses.Survival and mutation analyses led to the creation of a nomo-gram for predicting patient prognosis.Furthermore,we investigated the role of GRINA,a ferroptosis-related gene,through functional assays,including cell proliferation,colony formation,and metastatic potential analyses.We also assessed mito-chondrial abnormalities,intracellular iron,and ROS levels in GRINA-knockdown cells.Results The developed ferroptosis-related model classified HCC patients into risk groups,revealing notable survival dispari-ties.High-risk patients presented increased immune checkpoint gene expression.The nomogram revealed robust prognostic accuracy.Additionally,we found that GRINA suppression reduced HCC cell proliferation,colony formation,and metastatic potential.Cells with GRINA knockdown presented mitochondrial abnormalities and increased intracellular iron and ROS levels.Conclusions By analysing multiomics sequencing data,we established a connection between ferroptosis-related risk groups and the tumor immune microenvironment.These findings provide novel insights into the role of ferroptosis in HCC and suggest that GRINA inhibition is a potential therapeutic strategy,leading to mitochondrial damage and the induction of fer-roptosis in HCC cell lines.
