AIM:To investigate the causal effect of obesity on cataract risk and explores the potential mediating roles of metabolites using Mendelian randomization(MR).METHODS:Summary-level data from large-scale genome-wide asso...AIM:To investigate the causal effect of obesity on cataract risk and explores the potential mediating roles of metabolites using Mendelian randomization(MR).METHODS:Summary-level data from large-scale genome-wide association studies to examine the relationship between obesity and cataract were utilized.Obesity-related traits,including body mass index(BMI),waist-to-hip ratio(WHR),and waist circumference(WC).A two-sample MR approach was employed to assess the causal effect of obesity on cataract risk,while potential mediators were identified from suitable genome-wide association studies(GWAS)datasets.Additionally,a metabolic pathway analysis was conducted.RESULTS:An increase of 1 standard deviation(SD)in BMI,WHR,and WC was associated with a significantly higher risk of cataract(BMI:odds ratio(OR)1.0017,95%confidence interval(CI):1.0001-1.0032,P=0.0320;WHR:OR 1.0029,95%CI:1.0006-1.0051,P=0.0129;WC:OR 1.0020,95%CI:1.0001-1.0038,P=0.0390].These associations remained robust after adjusting for confounding factors in multivariable MR analysis.Furthermore,a two-step MR analysis identified eight potential metabolic mediators,with one mediator showing a significant causal role in the relationship between obesity and cataract.CONCLUSION:This work highlights the importance of addressing obesity as a modifiable risk factor for cataracts,particularly through metabolic pathways.展开更多
Background Recent studies have suggested a potential role of the oral microbiome in the development of cardiovascular diseases.This study aims to investigate the association between oral microbiota and cardiovascular ...Background Recent studies have suggested a potential role of the oral microbiome in the development of cardiovascular diseases.This study aims to investigate the association between oral microbiota and cardiovascular disease risk,including atrial fibrillation,myocardial infarction,chronic heart failure,and hypertension.Methods We analyzed GWAS data from East Asian populations'oral microbiome,involving 2,017 tongue and 1,915 saliva samples from 2,984 individuals with whole-genome sequencing.Additionally,we sourced cardiovascular disease GWAS data from NBDC,including atrial fibrillation(8,180 cases,28,621 controls),myocardial infarction(14,992 cases,146,214 controls),chronic heart failure(10,540 cases,168,186 controls),and systolic blood pressure(145,505 individuals).Results Several oral microbiota taxa were found to be significantly associated with cardiovascular disease outcomes.Specific microbiota,such as Centipeda,Corynebacterium,and Pseudomonas E,were negatively correlated with heart failure.In contrast,taxa like Neisseria D and Actinomyces were associated with an increased risk of atrial fibrillation and myocardial infarction.Additionally,certain oral microbiota showed correlations with changes in blood pressure,highlighting their potential role in hypertension.Conclusion Our findings suggest that the oral microbiota may influence the development and progression of cardiovascular diseases,providing new insights into the potential impact of oral health on cardiovascular risk.展开更多
[Objectives]To investigate the potential causal relationship between psoriasis and common mental disorders,and to provide genetic epidemiological evidence for the early intervention of mental comorbidities.[Methods]Ba...[Objectives]To investigate the potential causal relationship between psoriasis and common mental disorders,and to provide genetic epidemiological evidence for the early intervention of mental comorbidities.[Methods]Based on publicly available large-scale GWAS data,a bidirectional Mendelian randomization(MR)approach was employed to assess the causal associations between psoriasis and major depressive disorder(MDD),bipolar disorder,schizophrenia,and anxiety disorders.The inverse variance weighted(IVW)method served as the primary analytical tool,supplemented by sensitivity analyses using MR-Egger and weighted median methods.Additionally,a subgroup analysis was conducted for psoriatic arthritis(PsA).[Results]Forward MR analysis revealed a significant positive causal association between the genetic predisposition to psoriasis and bipolar disorder as well as MDD,whereas no significant causal relationship was observed with schizophrenia or anxiety disorders.The reverse MR analysis found no causal effect of mental disorders on psoriasis.Subgroup analysis of PsA indicated that its genetic predisposition was significantly associated with the risk of bipolar disorder.The results of various sensitivity analyses and pleiotropy tests supported the robustness of the conclusions.[Conclusions]This study provides genetic evidence supporting a causal link between psoriasis and both MDD and bipolar disorder.In particular,patients with PsA are at a higher risk of developing bipolar disorder,highlighting the need to strengthen early screening and intervention for mental health in clinical management.展开更多
AIM:To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization(MR)approach.METHODS:Publicly available genome-wide association study(GWAS)da...AIM:To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization(MR)approach.METHODS:Publicly available genome-wide association study(GWAS)datasets were utilized for this two-sample MR analysis.Inflammatory cytokine-related GWAS data were extracted from The University of Bristol’s Research Data Repository,and myopia-related GWAS data were obtained from the FinnGen project.Single nucleotide polymorphisms(SNPs)associated with inflammatory cytokines were systematically selected as instrumental variables(IVs)based on three rigorous criteria:relevance,independence,and exclusion of pleiotropy.Five MR methods were employed for causal inference:the inverse-variance weighted(IVW)method as the primary analysis,supplemented by MREgger regression,weighted median estimator,simple mode,and weighted mode approaches.Sensitivity analyses were performed to evaluate the robustness of the causal estimates.RESULTS:A total of 773 myopia-associated SNPs were identified.MR analysis revealed that higher levels of macrophage inflammatory protein 1-α(MIP-1α)were associated with a 17%reduced risk of myopia[odds ratio(OR)=0.83;95%confidence interval(CI):0.69-0.99;P<0.05].In contrast,elevated levels of eotaxin(OR=1.26;95%CI:1.07-1.47;P<0.01),stromal cell-derived factor-1α(SDF-1α;OR=1.68;95%CI:1.08-2.62;P<0.05),and interleukin-2 receptor subunit alpha(IL-2Rα;OR=1.25;95%CI:1.01-1.53;P<0.05)were significantly associated with an increased risk of myopia.Sensitivity analyses confirmed the reliability of these results.CONCLUSION:This study provides evidence supporting a causal relationship between specific inflammatory cytokines and myopia.MIP-1αmay act as a protective factor against myopia,while eotaxin,SDF-1α,and IL-2Rαare potential risk factors for myopia.These findings emphasize the critical role of inflammatory pathways in the pathogenesis of myopia,offering novel insights for the development of preventive and therapeutic strategies for myopia.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
Objective Previous studies link lower body mass index(BMI)with increased obsessive-compulsive disorder(OCD)risk,yet other body mass indicators may be more etioloically relevant.We dissected the causal association betw...Objective Previous studies link lower body mass index(BMI)with increased obsessive-compulsive disorder(OCD)risk,yet other body mass indicators may be more etioloically relevant.We dissected the causal association between body fat mass(FM)and OCD.Methods Summary statistics from genome-wide association studies of European ancestry were utilized to conduct two-sample Mendelian randomization analysis.Heterogeneity,horizontal pleiotropy,and sensitivity analyses were performed to assess the robustness.Results The inverse variance weighting method demonstrated that a genetically predicted decrease in FM was causally associated with an increased OCD risk[odds ratio(OR)=0.680,95%confidence interval(CI):0.528–0.875,P=0.003].Similar estimates were obtained using the weighted median approach(OR=0.633,95%CI:0.438–0.915,P=0.015).Each standard deviation increases in genetically predicted body fat percentage corresponded to a reduced OCD risk(OR=0.638,95%CI:0.455–0.896,P=0.009).The sensitivity analysis confirmed the robustness of these findings with no outlier instrument variables identified.Conclusion The negative causal association between FM and the risk of OCD suggests that the prevention or treatment of mental disorders should include not only the control of BMI but also fat distribution and body composition.展开更多
AIM:To comprehensively assess the relationship between asthma and myopia based on the National Health and Nutrition Examination Survey(NHANES)database combined with Mendelian randomization(MR).METHODS:Initially,20497 ...AIM:To comprehensively assess the relationship between asthma and myopia based on the National Health and Nutrition Examination Survey(NHANES)database combined with Mendelian randomization(MR).METHODS:Initially,20497 subjects from the complete questionnaire cycle in the NHANES database from 2005 to 2008 were included.By exclusion criteria,8460 subjects were screened with 1676 myopia samples and 6784 control samples.Subsequently,baseline characteristics,association analyses,risk stratification analyses,and receive operating characteristic curve(ROC)were used to investigate the associations between covariates and myopia.Then,the causal relationship was explored in depth by MR analysis,and was estimated the reliability by sensitivity analyses and directionality tests.RESULTS:Baseline characteristics illustrated a significant difference between myopia and controls for both asthma and covariates(excluding gender;P<0.05).The results in all three models indicated that asthma was strongly associated with myopia and the effect on myopia was not significantly confounded by other covariates[model 3:odd ratio(OR)=1.31;95%CI=1.07-1.62;P=0.0133].The risk stratification analysis again verified that asthma remained strongly associated with myopia and was a risk factor for myopia(P<0.05,OR>1).ROC proved that the model was accurate in its prediction[area under curve(AUC)=0.7].Subsequently,the causal relationship between them was statistically significant(P<0.05)according to the inverse variance weighted(IVW)method in MR.Scatterplot showed that asthma and myopia had significant positive causality and were not affected by confounders.Forest plot displayed an increasing risk of myopia on asthma(OR>1).The funnel plot demonstrated compliance with Mendel’s second law.Sensitivity analysis and directional analysis further confirmed the confidence of the MR analysis results and a unidirectional causal relationship between them.CONCLUSION:A significant association and causality between asthma and myopia is found through the NHANES database and MR analysis,which is important implications for public health policy development and clinical practice.展开更多
Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroa...Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke.The PubMed,EMBASE,Web of Science,CENTRAL,and CINAHL databases were comprehensively searched up to May 1,2024.This review included articles on preclinical investigations of the efficacy and mechanisms of electroacupuncture in treating ischemic stroke.Data from 70 eligible studies were analyzed in Stata 18.0,using a random-effects model to calculate the standardized mean difference(Hedge’s g).The risk of bias was assessed using RevMan 5.4 software,and the quality of evidence was rated according to the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)system.Subgroup analyses were conducted to test the consistency of the results and sensitivity analyses were used to assess their robustness.The quality assessment revealed that most studies adequately handled incomplete data and selective reporting.However,several methodological limitations were identified:only 4 studies demonstrated a low risk of allocation concealment,26 achieved a low risk of outcome assessment bias,and 9 had a high risk of randomization bias.Additionally,there was an unclear risk regarding participant blinding and other methodological aspects.The GRADE assessment rated 12 outcomes as moderate quality and 6 as low quality.The mechanisms of electroacupuncture treatment for ischemic stroke can be categorized as five primary pathways:(1)Electroacupuncture significantly reduced infarct volume and apoptotic cell death(P<0.01)in ischemic stroke models;(2)electroacupuncture significantly decreased the levels of pro-inflammatory factors(P<0.01)while increasing the levels of anti-inflammatory factors(P=0.02);(3)electroacupuncture reduced the levels of oxidative stress indicators(P<0.01)and enhanced the expression of antioxidant enzymes(P<0.01);(4)electroacupuncture significantly promoted nerve regeneration(P<0.01);and(5)electroacupuncture influenced blood flow remodeling(P<0.01)and angiogenesis(P<0.01).Subgroup analyses indicated that electroacupuncture was most effective in the transient middle cerebral artery occlusion model(P<0.01)and in post-middle cerebral artery occlusion intervention(P<0.01).Dispersive waves were found to outperform continuous waves with respect to neuroprotection and anti-inflammatory effects(P<0.01),while scalp acupoints demonstrated greater efficacy than body acupoints(P<0.01).The heterogeneity among the included studies was minimal,and sensitivity analyses indicated stable results.Their methodological quality was generally satisfactory.In conclusion,electroacupuncture is effective in treating cerebral ischemia by modulating cell apoptosis,oxidative stress,inflammation,stroke-induced nerve regeneration,blood flow remodeling,and angiogenesis.The efficacy of electroacupuncture may be influenced by factors such as the middle cerebral artery occlusion model,the timing of intervention onset,waveform,and acupoint selection.Despite the moderate to low quality of evidence,these findings suggest that electroacupuncture has clinical potential for improving outcomes in ischemic stroke.展开更多
Under sustained strong stochastic impact loads,floating-supported friction plates are susceptible to the formation of fatigue cracks that propagate along the rim.The nonlinearity and randomness introduced by the crack...Under sustained strong stochastic impact loads,floating-supported friction plates are susceptible to the formation of fatigue cracks that propagate along the rim.The nonlinearity and randomness introduced by the cracked teeth participating in the impacts significantly influence the service life and reliability of the transmission system.In this paper,an improved stiffness excitation modeling method is developed for friction plate teeth with rim cracks.It overcomes the limitations of traditional approaches that fail to accurately assess the narrow-band,large-diameter friction plate teeth with rim cracks due to constraints imposed by boundary conditions.Then,an original dynamic impact model for the floating-supported friction plate and inner hub system is proposed,incorporating the effects of bending-torsional-axial-tilting coupled motions on tooth mesh excitations and dynamic responses.This model addresses the limitations of conventional models that only consider bending-torsion coupling,thereby providing a more comprehensive representation of the system's multi-dimensional dynamic behavior.The effects of the crack propagation depth and the number of cracked teeth on the stochastic impact characteristics and vibration responses of the system are investigated.Furthermore,finite element simulations and experimental tests are conducted to validate the cracked tooth stiffness excitations and dynamic impact responses,respectively.The proposed model is anticipated to provide both a theoretical foundation and practical guidance for fault diagnosis and reliability assessment of clutch friction plates.展开更多
Objectives This study aimed to design and evaluate a detection system for the accidental dislodgement of head-and-neck medical supplies through hand position recognition and tracking in Intensive Care Unit(ICU)patient...Objectives This study aimed to design and evaluate a detection system for the accidental dislodgement of head-and-neck medical supplies through hand position recognition and tracking in Intensive Care Unit(ICU)patients.Methods We conducted a single-center,prospective,parallel-group feasibility randomized controlled trial.We recruited 80 participants using convenience sampling from the ICU of a hospital in Ningbo City,Zhejiang Province,between March 2025 and June 2025,and they were randomly assigned to either the control group(routine care)or the intervention group(routine care plus image recognition-based detection system).The system continuously tracked patients’hand positions via bedside cameras and generated real-time alarms when hands entered predefined risk zones,notifying on-duty nurses to enable early intervention.System stability was assessed by continuous system uptime;system performance and clinical feasibility were evaluated by the frequencies of risk actions and accidental dislodgement of medical supplies(ADMS).Results All 80 participants completed the intervention,with 40 patients in each group.The baseline characteristics and median observation time of the two groups were balanced(intervention group:48 h/patient vs.control group:49 h/patient).Compared with the control group,the intervention group showed fewer ADMS(2/40 vs.9/40)and detected more risk actions per 100 h(36 vs.25);all system-detected events had corroborating images with complete concordance on manual review,and all nurse-recorded hand-contact events were accurately captured.Conclusions The study demonstrated that the image recognition-based detection system can function stably in clinical settings,providing accurate and continuous surveillance while supporting the early detection of risk actions.By reducing the observation burden and offering real-time cognitive support,the system complements routine nursing care and serves as an additional safety measure in ICU practice.With further optimization and larger multicenter validation,this approach could have the potential to make a significant contribution to the development of smart ICUs and the broader digital transformation of nursing care.展开更多
Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods ...Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.展开更多
Infections with the coronavirus disease 2019(COVID-19)and disorders of the heart and blood vessels are causally related.To ascertain the causal relationship between COVID-19 and cardiovascular disease(CVD),we carried ...Infections with the coronavirus disease 2019(COVID-19)and disorders of the heart and blood vessels are causally related.To ascertain the causal relationship between COVID-19 and cardiovascular disease(CVD),we carried out a Mendelian randomization(MR)study through a method known as inverse variance weighting(IVW).When analyzing multiple SNPs,MR can meta-aggregate the effects of multiple loci by using IVW meta-pooling method.The weighted median(WM)is the median of the distribution function obtained by ranking all individual SNP effect values according to their weights.WM yields robust estimates when at least 50%of the information originates from valid instrumental variables(IVs).Directed gene pleiotropy in the included IVs is permitted because MR–Egger does not require a regression straight line through the origin.For MR estimation,IVW,WM and MR-Egger were employed.Sensitivity analysis was conducted using funnel plots,Cochran's Q test,MR–Egger intercept test,MR–PRESSO,and leave-one-out analysis.SNPs related to exposure to COVID-19 and CVD were compiled.CVD for COVID-19 infection,COVID-19 laboratory/self-reported negative,and other very severe respiratory diagnosis and population were randomly assigned using MR.The COVID-19 laboratory/self-reported negative results and other very severe respiratory confirmed cases versus MR analysis of CVD in the population(p>0.05);COVID-19 infection to CVD(p?0.033,OR?1.001,95%CI:1.000–1.001);and the MR–Egger results indicated that COVID-19 infection was associated with CVD risk.This MR study provides preliminary evidence for the validity of the causal link between COVID-19 infection and CVD.展开更多
Objective Observational studies have shown inconsistent associations of loneliness or social isolation(SI)with ischemic heart disease(IHD),with unknown mediators.Methods Using data from genome-wide association studies...Objective Observational studies have shown inconsistent associations of loneliness or social isolation(SI)with ischemic heart disease(IHD),with unknown mediators.Methods Using data from genome-wide association studies of predominantly European ancestry,we performed a bidirectional two-sample Mendelian Randomization(MR)study to estimate causal effects of loneliness(N=487,647)and SI traits on IHD(N=184,305).SI traits included whether individuals lived alone,participated in various types of social activities,and how often they had contact with friends or family(N=459,830 to 461,369).A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators,including metabolic,behavioral and psychological factors.Results Loneliness increased IHD risk(OR=2.129;95%confidence interval[CI]:1.380 to 3.285),mediated by body fat percentage,waist-hip ratio,total cholesterol,and low-density lipoprotein cholesterol.For SI traits,only fewer social activities increased IHD risk(OR=1.815;95%CI:1.189 to 2.772),mediated by hypertension,high-density lipoprotein cholesterol,triglycerides,fasting insulin,and smoking cessation.No reverse causality of IHD with loneliness and SI was found.Conclusion These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD,with several mediators as prioritized targets for intervention.展开更多
Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether k...Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether key metabolite levels modified the GC primary prevention effects.Methods:Plasma metabolites associated with GC risk were identified through a case-control study.Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial(SIT),a nested case-control study of the Mass Intervention Trial in Linqu,Shandong province(MITS),China,the UK Biobank,and the Finn Gen project.Results:A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population(SIT:HR=1.26 per 1 SD change,95%CI:1.07±1.49;MITS:HR=1.07,95%CI:1.00±1.14)and an increased gastric adenocarcinoma risk in Finn Gen(OR=1.68,95%CI:1.16±2.45).Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level(P-interaction=0.098)and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level(P-interaction=0.02).Conclusions:Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention.Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.展开更多
Objective Vitamin deficiencies,particularly in vitamins A,B12,and D,are prevalent across populations and contribute significantly to a range of health issues.While these deficiencies are well documented,the underlying...Objective Vitamin deficiencies,particularly in vitamins A,B12,and D,are prevalent across populations and contribute significantly to a range of health issues.While these deficiencies are well documented,the underlying etiology remains complex.Recent studies suggest a close link between the gut microbiota and the synthesis,absorption,and metabolism of these vitamins.However,the specific causal relationships between the gut microbiota composition and vitamin deficiencies remain poorly understood.Identifying key bacterial species and understanding their role in vitamin metabolism could provide critical insights for targeted interventions.Methods We conducted a two-sample Mendelian randomization(MR)study to assess the causal relationship between the gut microbiota and vitamin deficiencies(A,B12,D).The genome-wide association study data for vitamin deficiencies were sourced from the FinnGen biobank,and the gut microbiota data were from the MiBioGen consortium.MR analyses included inverse variance-weighted(IVW),MR‒Egger,weighted median,and weighted mode approaches.Sensitivity analyses and reverse causality assessments were performed to ensure robustness and validate the findings.Results After FDR adjustment,vitamin B12 deficiency was associated with the class Verrucomicrobiae,order Verrucomicrobiales,family Verrucomicrobiaceae,and genus Akkermansia.Vitamin A deficiency was associated with the phylum Firmicutes and the genera Fusicatenibacter and Ruminiclostridium 6.Additional associations for vitamin B12 deficiency included the Enterobacteriaceae and Rhodospirillaceae and the genera Coprococcus 2,Lactococcus,and Ruminococcaceae UCG002.Vitamin D deficiency was associated with the genera Allisonella,Eubacterium,and Tyzzerella 3.Lachnospiraceae and Lactococcus were common risk factors for both B12 and D deficiency.Sensitivity analyses confirmed the robustness of the findings against heterogeneity and horizontal pleiotropy,and reverse MR tests indicated no evidence of reverse causality.Conclusions Our findings reveal a possible causal relationship between specific gut microbiota characteristics and vitamin A,B12 and D deficiencies,providing a theoretical basis for addressing these nutritional deficiencies through the modulation of the gut microbiota in the future and laying the groundwork for related interventions.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
Background:Cytomegalovirus(CMV)reactivation is linked to a high mortality rate,especially among the elderly.Prior research suggests that renin-angiotensin system(RAS)inhibitors may influence both the onset and prognos...Background:Cytomegalovirus(CMV)reactivation is linked to a high mortality rate,especially among the elderly.Prior research suggests that renin-angiotensin system(RAS)inhibitors may influence both the onset and prognosis of pneumonia.This study aims to examine the causal relationship between RAS inhibitor use and the risk of CMV pneumonia using Mendelian randomization(MR)analysis.Methods:We conducted an analysis using data from two genome-wide association studies(GWAS)involving individuals of European ancestry.This dataset included individuals treated with RAS inhibitors and those with CMV pneumonia.We assessed the relationship between RAS inhibitor use and CMV pneumonia risk using the inverse variance weighted(IVW)method.The results were further evaluated for pleiotropy,heterogeneity,and robustness.Results:The Mendelian randomization(MR)analysis revealed a causal relationship between RAS inhibitor use and an increased risk of CMV pneumonia(IVW:odds ratio[OR]=2.73;95%confidence interval[CI]=1.11-6.73;P=0.028).Conclusions:Our finding indicate a positive causal relationship between the use of RAS inhibitors and the onset of CMV pneumonia.展开更多
Objective:Gut microbiota(GM)and blood metabolites are associated with the development of urticaria,yet their specific causal relationships in East Asian populations remain unclear.This study aims to elucidate the caus...Objective:Gut microbiota(GM)and blood metabolites are associated with the development of urticaria,yet their specific causal relationships in East Asian populations remain unclear.This study aims to elucidate the causal and mediating relationships among GM,blood metabolites,and urticaria in East Asians using Mendelian randomization(MR)analysis.Methods:Summary-level statistics for 500 GM taxa,112 blood metabolites,and urticaria were obtained from publicly available Genome-Wide Association Studies(GWAS)datasets.Bidirectional MR analyses were performed to examine causal associations among the GM,blood metabolites,and urticaria.The inverse variance weighted(IVW)method served as the primary analytical approach,supplemented by MR-Egger,weighted median,simple mode,and weighted mode methods.Sensitivity analyses included heterogeneity tests,horizontal pleiotropy assessments,and leave-one-out analyses.Mediation analysis was conducted to evaluate the potential mediating effects of blood metabolites on the causal pathways between GM and urticaria.Results:MR analyses identified 12 GM taxa exhibiting significant causal effects on urticaria susceptibility.Nine taxa,such as MF0017_galactose_degradation(OR=1.461,95%CI 1.098 to 1.944,P=0.009),were associated with increased urticaria risk.Three taxa,such as MF0001_arabinoxylan_degradation(OR=0.846,95%CI 0.737 to 0.973,P=0.019),showed protective effects with increased abundance.Additionally,6 blood metabolites demonstrated causal associations with urticaria.Notably,the risk of developing urticaria increases with rising fasting plasma glucose(FPG)levels(OR=1.971,95%CI 1.089 to 3.567,P=0.025).Mediation analysis further demonstrated that FPG partially mediated the protective effect of MF0001_arabinoxylan_degradation on urticaria,accounting for 11.30%of the total effect.Conclusion:This study has delineated specific GM taxa and blood metabolites that hold causal relevance to urticaria in East Asian populations.Notably,arabinogalactan degradation potentially mitigates urticaria risk via reducing FPG concentrations,offering genetic evidence to support therapeutic strategies targeting GM modulation and glucose regulation.展开更多
Domain randomization is a widely adopted technique in deep reinforcement learning(DRL)to improve agent generalization by exposing policies to diverse environmental conditions.This paper investigates the impact of diff...Domain randomization is a widely adopted technique in deep reinforcement learning(DRL)to improve agent generalization by exposing policies to diverse environmental conditions.This paper investigates the impact of different reset strategies,normal,non-randomized,and randomized,on agent performance using the Deep Deterministic Policy Gradient(DDPG)and Twin Delayed DDPG(TD3)algorithms within the CarRacing-v2 environment.Two experimental setups were conducted:an extended training regime with DDPG for 1000 steps per episode across 1000 episodes,and a fast execution setup comparing DDPG and TD3 for 30 episodes with 50 steps per episode under constrained computational resources.A step-based reward scaling mechanism was applied under the randomized reset condition to promote broader state exploration.Experimental results showthat randomized resets significantly enhance learning efficiency and generalization,with DDPG demonstrating superior performance across all reset strategies.In particular,DDPG combined with randomized resets achieves the highest smoothed rewards(reaching approximately 15),best stability,and fastest convergence.These differences are statistically significant,as confirmed by t-tests:DDPG outperforms TD3 under randomized(t=−101.91,p<0.0001),normal(t=−21.59,p<0.0001),and non-randomized(t=−62.46,p<0.0001)reset conditions.The findings underscore the critical role of reset strategy and reward shaping in enhancing the robustness and adaptability of DRL agents in continuous control tasks,particularly in environments where computational efficiency and training stability are crucial.展开更多
AIM:To investigate the causal relationship between dietary intake and myopia using Mendelian randomization(MR)analysis.METHODS:Genome-wide association study(GWAS)data from the IEU Open GWAS database were utilized to e...AIM:To investigate the causal relationship between dietary intake and myopia using Mendelian randomization(MR)analysis.METHODS:Genome-wide association study(GWAS)data from the IEU Open GWAS database were utilized to examine associations between myopia and various dietary factors.MR analysis,incorporating both univariable and multivariable approaches,assessed the impact of food intake on myopia risk through five analytical methods,with inverse variance weighted(IVW)serving as the primary reference.Sensitivity analyses,including heterogeneity assessment,horizontal pleiotropy evaluation,and leave-oneout analysis,were conducted to validate the MR findings.RESULTS:Univariable MR analysis identified a causal link between food intake and myopia.Consumption of breaded fish,canned soup,sweet biscuits,and certain fruits correlated with a lower risk of myopia,whereas intake of low-calorie hot chocolate and cereal was associated with an increased risk.Multivariable MR analysis further confirmed that breaded fish consumption exerted a direct protective effect against myopia,particularly when consumed alongside other dietary components.These findings highlight the intricate interplay between specific dietary factors and myopia development,offering valuable insights for further research.CONCLUSION:MR analysis provides evidence supporting a potential causal relationship between breaded fish intake and myopia,underscoring its relevance in targeted myopia prevention strategies.展开更多
基金Supported by the National Natural Science Foundation of China(No.82501261)Medical Research Projects of the Jiangsu Provincial Health Commission(No.M2024041).
文摘AIM:To investigate the causal effect of obesity on cataract risk and explores the potential mediating roles of metabolites using Mendelian randomization(MR).METHODS:Summary-level data from large-scale genome-wide association studies to examine the relationship between obesity and cataract were utilized.Obesity-related traits,including body mass index(BMI),waist-to-hip ratio(WHR),and waist circumference(WC).A two-sample MR approach was employed to assess the causal effect of obesity on cataract risk,while potential mediators were identified from suitable genome-wide association studies(GWAS)datasets.Additionally,a metabolic pathway analysis was conducted.RESULTS:An increase of 1 standard deviation(SD)in BMI,WHR,and WC was associated with a significantly higher risk of cataract(BMI:odds ratio(OR)1.0017,95%confidence interval(CI):1.0001-1.0032,P=0.0320;WHR:OR 1.0029,95%CI:1.0006-1.0051,P=0.0129;WC:OR 1.0020,95%CI:1.0001-1.0038,P=0.0390].These associations remained robust after adjusting for confounding factors in multivariable MR analysis.Furthermore,a two-step MR analysis identified eight potential metabolic mediators,with one mediator showing a significant causal role in the relationship between obesity and cataract.CONCLUSION:This work highlights the importance of addressing obesity as a modifiable risk factor for cataracts,particularly through metabolic pathways.
基金supported by the National Natural Science Foundation of China(Grant No.82500432)the Heilongjiang Provincial Health Commission Scientific Research Project(Grant No.20240303010111).
文摘Background Recent studies have suggested a potential role of the oral microbiome in the development of cardiovascular diseases.This study aims to investigate the association between oral microbiota and cardiovascular disease risk,including atrial fibrillation,myocardial infarction,chronic heart failure,and hypertension.Methods We analyzed GWAS data from East Asian populations'oral microbiome,involving 2,017 tongue and 1,915 saliva samples from 2,984 individuals with whole-genome sequencing.Additionally,we sourced cardiovascular disease GWAS data from NBDC,including atrial fibrillation(8,180 cases,28,621 controls),myocardial infarction(14,992 cases,146,214 controls),chronic heart failure(10,540 cases,168,186 controls),and systolic blood pressure(145,505 individuals).Results Several oral microbiota taxa were found to be significantly associated with cardiovascular disease outcomes.Specific microbiota,such as Centipeda,Corynebacterium,and Pseudomonas E,were negatively correlated with heart failure.In contrast,taxa like Neisseria D and Actinomyces were associated with an increased risk of atrial fibrillation and myocardial infarction.Additionally,certain oral microbiota showed correlations with changes in blood pressure,highlighting their potential role in hypertension.Conclusion Our findings suggest that the oral microbiota may influence the development and progression of cardiovascular diseases,providing new insights into the potential impact of oral health on cardiovascular risk.
文摘[Objectives]To investigate the potential causal relationship between psoriasis and common mental disorders,and to provide genetic epidemiological evidence for the early intervention of mental comorbidities.[Methods]Based on publicly available large-scale GWAS data,a bidirectional Mendelian randomization(MR)approach was employed to assess the causal associations between psoriasis and major depressive disorder(MDD),bipolar disorder,schizophrenia,and anxiety disorders.The inverse variance weighted(IVW)method served as the primary analytical tool,supplemented by sensitivity analyses using MR-Egger and weighted median methods.Additionally,a subgroup analysis was conducted for psoriatic arthritis(PsA).[Results]Forward MR analysis revealed a significant positive causal association between the genetic predisposition to psoriasis and bipolar disorder as well as MDD,whereas no significant causal relationship was observed with schizophrenia or anxiety disorders.The reverse MR analysis found no causal effect of mental disorders on psoriasis.Subgroup analysis of PsA indicated that its genetic predisposition was significantly associated with the risk of bipolar disorder.The results of various sensitivity analyses and pleiotropy tests supported the robustness of the conclusions.[Conclusions]This study provides genetic evidence supporting a causal link between psoriasis and both MDD and bipolar disorder.In particular,patients with PsA are at a higher risk of developing bipolar disorder,highlighting the need to strengthen early screening and intervention for mental health in clinical management.
文摘AIM:To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization(MR)approach.METHODS:Publicly available genome-wide association study(GWAS)datasets were utilized for this two-sample MR analysis.Inflammatory cytokine-related GWAS data were extracted from The University of Bristol’s Research Data Repository,and myopia-related GWAS data were obtained from the FinnGen project.Single nucleotide polymorphisms(SNPs)associated with inflammatory cytokines were systematically selected as instrumental variables(IVs)based on three rigorous criteria:relevance,independence,and exclusion of pleiotropy.Five MR methods were employed for causal inference:the inverse-variance weighted(IVW)method as the primary analysis,supplemented by MREgger regression,weighted median estimator,simple mode,and weighted mode approaches.Sensitivity analyses were performed to evaluate the robustness of the causal estimates.RESULTS:A total of 773 myopia-associated SNPs were identified.MR analysis revealed that higher levels of macrophage inflammatory protein 1-α(MIP-1α)were associated with a 17%reduced risk of myopia[odds ratio(OR)=0.83;95%confidence interval(CI):0.69-0.99;P<0.05].In contrast,elevated levels of eotaxin(OR=1.26;95%CI:1.07-1.47;P<0.01),stromal cell-derived factor-1α(SDF-1α;OR=1.68;95%CI:1.08-2.62;P<0.05),and interleukin-2 receptor subunit alpha(IL-2Rα;OR=1.25;95%CI:1.01-1.53;P<0.05)were significantly associated with an increased risk of myopia.Sensitivity analyses confirmed the reliability of these results.CONCLUSION:This study provides evidence supporting a causal relationship between specific inflammatory cytokines and myopia.MIP-1αmay act as a protective factor against myopia,while eotaxin,SDF-1α,and IL-2Rαare potential risk factors for myopia.These findings emphasize the critical role of inflammatory pathways in the pathogenesis of myopia,offering novel insights for the development of preventive and therapeutic strategies for myopia.
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supported by the Yanzhao Gold Talent Project of Hebei Province(NO.HJZD202506)。
文摘Objective Previous studies link lower body mass index(BMI)with increased obsessive-compulsive disorder(OCD)risk,yet other body mass indicators may be more etioloically relevant.We dissected the causal association between body fat mass(FM)and OCD.Methods Summary statistics from genome-wide association studies of European ancestry were utilized to conduct two-sample Mendelian randomization analysis.Heterogeneity,horizontal pleiotropy,and sensitivity analyses were performed to assess the robustness.Results The inverse variance weighting method demonstrated that a genetically predicted decrease in FM was causally associated with an increased OCD risk[odds ratio(OR)=0.680,95%confidence interval(CI):0.528–0.875,P=0.003].Similar estimates were obtained using the weighted median approach(OR=0.633,95%CI:0.438–0.915,P=0.015).Each standard deviation increases in genetically predicted body fat percentage corresponded to a reduced OCD risk(OR=0.638,95%CI:0.455–0.896,P=0.009).The sensitivity analysis confirmed the robustness of these findings with no outlier instrument variables identified.Conclusion The negative causal association between FM and the risk of OCD suggests that the prevention or treatment of mental disorders should include not only the control of BMI but also fat distribution and body composition.
基金Supported by the Hainan Provincial Natural Science Foundation of China(No.825RC898)Hainan Province Clinical Medical Center。
文摘AIM:To comprehensively assess the relationship between asthma and myopia based on the National Health and Nutrition Examination Survey(NHANES)database combined with Mendelian randomization(MR).METHODS:Initially,20497 subjects from the complete questionnaire cycle in the NHANES database from 2005 to 2008 were included.By exclusion criteria,8460 subjects were screened with 1676 myopia samples and 6784 control samples.Subsequently,baseline characteristics,association analyses,risk stratification analyses,and receive operating characteristic curve(ROC)were used to investigate the associations between covariates and myopia.Then,the causal relationship was explored in depth by MR analysis,and was estimated the reliability by sensitivity analyses and directionality tests.RESULTS:Baseline characteristics illustrated a significant difference between myopia and controls for both asthma and covariates(excluding gender;P<0.05).The results in all three models indicated that asthma was strongly associated with myopia and the effect on myopia was not significantly confounded by other covariates[model 3:odd ratio(OR)=1.31;95%CI=1.07-1.62;P=0.0133].The risk stratification analysis again verified that asthma remained strongly associated with myopia and was a risk factor for myopia(P<0.05,OR>1).ROC proved that the model was accurate in its prediction[area under curve(AUC)=0.7].Subsequently,the causal relationship between them was statistically significant(P<0.05)according to the inverse variance weighted(IVW)method in MR.Scatterplot showed that asthma and myopia had significant positive causality and were not affected by confounders.Forest plot displayed an increasing risk of myopia on asthma(OR>1).The funnel plot demonstrated compliance with Mendel’s second law.Sensitivity analysis and directional analysis further confirmed the confidence of the MR analysis results and a unidirectional causal relationship between them.CONCLUSION:A significant association and causality between asthma and myopia is found through the NHANES database and MR analysis,which is important implications for public health policy development and clinical practice.
基金supported by the National Natural Science Foundation of China,Nos.82174496(to NW),82374574(to NW),82302865(to LL)Shanghai Science and Technology Committee Sailing Program,Nos.23YF1403800(to LL),23YF1405200(to YX)Shanghai Hospital Development Center Foundation-Shanghai Municipal Hospital Rehabilitation Medicine Specialty Alliance,No.SHDC22023304(to YW).
文摘Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke.The PubMed,EMBASE,Web of Science,CENTRAL,and CINAHL databases were comprehensively searched up to May 1,2024.This review included articles on preclinical investigations of the efficacy and mechanisms of electroacupuncture in treating ischemic stroke.Data from 70 eligible studies were analyzed in Stata 18.0,using a random-effects model to calculate the standardized mean difference(Hedge’s g).The risk of bias was assessed using RevMan 5.4 software,and the quality of evidence was rated according to the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)system.Subgroup analyses were conducted to test the consistency of the results and sensitivity analyses were used to assess their robustness.The quality assessment revealed that most studies adequately handled incomplete data and selective reporting.However,several methodological limitations were identified:only 4 studies demonstrated a low risk of allocation concealment,26 achieved a low risk of outcome assessment bias,and 9 had a high risk of randomization bias.Additionally,there was an unclear risk regarding participant blinding and other methodological aspects.The GRADE assessment rated 12 outcomes as moderate quality and 6 as low quality.The mechanisms of electroacupuncture treatment for ischemic stroke can be categorized as five primary pathways:(1)Electroacupuncture significantly reduced infarct volume and apoptotic cell death(P<0.01)in ischemic stroke models;(2)electroacupuncture significantly decreased the levels of pro-inflammatory factors(P<0.01)while increasing the levels of anti-inflammatory factors(P=0.02);(3)electroacupuncture reduced the levels of oxidative stress indicators(P<0.01)and enhanced the expression of antioxidant enzymes(P<0.01);(4)electroacupuncture significantly promoted nerve regeneration(P<0.01);and(5)electroacupuncture influenced blood flow remodeling(P<0.01)and angiogenesis(P<0.01).Subgroup analyses indicated that electroacupuncture was most effective in the transient middle cerebral artery occlusion model(P<0.01)and in post-middle cerebral artery occlusion intervention(P<0.01).Dispersive waves were found to outperform continuous waves with respect to neuroprotection and anti-inflammatory effects(P<0.01),while scalp acupoints demonstrated greater efficacy than body acupoints(P<0.01).The heterogeneity among the included studies was minimal,and sensitivity analyses indicated stable results.Their methodological quality was generally satisfactory.In conclusion,electroacupuncture is effective in treating cerebral ischemia by modulating cell apoptosis,oxidative stress,inflammation,stroke-induced nerve regeneration,blood flow remodeling,and angiogenesis.The efficacy of electroacupuncture may be influenced by factors such as the middle cerebral artery occlusion model,the timing of intervention onset,waveform,and acupoint selection.Despite the moderate to low quality of evidence,these findings suggest that electroacupuncture has clinical potential for improving outcomes in ischemic stroke.
基金supported by the National Natural Science Foundation of China(Grant Nos.52505101,52475087,52475089,52365010)the Early-Career Young Scientists and Technologists Project of Jiangxi Province(Grant No.20252BEJ730175)。
文摘Under sustained strong stochastic impact loads,floating-supported friction plates are susceptible to the formation of fatigue cracks that propagate along the rim.The nonlinearity and randomness introduced by the cracked teeth participating in the impacts significantly influence the service life and reliability of the transmission system.In this paper,an improved stiffness excitation modeling method is developed for friction plate teeth with rim cracks.It overcomes the limitations of traditional approaches that fail to accurately assess the narrow-band,large-diameter friction plate teeth with rim cracks due to constraints imposed by boundary conditions.Then,an original dynamic impact model for the floating-supported friction plate and inner hub system is proposed,incorporating the effects of bending-torsional-axial-tilting coupled motions on tooth mesh excitations and dynamic responses.This model addresses the limitations of conventional models that only consider bending-torsion coupling,thereby providing a more comprehensive representation of the system's multi-dimensional dynamic behavior.The effects of the crack propagation depth and the number of cracked teeth on the stochastic impact characteristics and vibration responses of the system are investigated.Furthermore,finite element simulations and experimental tests are conducted to validate the cracked tooth stiffness excitations and dynamic impact responses,respectively.The proposed model is anticipated to provide both a theoretical foundation and practical guidance for fault diagnosis and reliability assessment of clutch friction plates.
文摘Objectives This study aimed to design and evaluate a detection system for the accidental dislodgement of head-and-neck medical supplies through hand position recognition and tracking in Intensive Care Unit(ICU)patients.Methods We conducted a single-center,prospective,parallel-group feasibility randomized controlled trial.We recruited 80 participants using convenience sampling from the ICU of a hospital in Ningbo City,Zhejiang Province,between March 2025 and June 2025,and they were randomly assigned to either the control group(routine care)or the intervention group(routine care plus image recognition-based detection system).The system continuously tracked patients’hand positions via bedside cameras and generated real-time alarms when hands entered predefined risk zones,notifying on-duty nurses to enable early intervention.System stability was assessed by continuous system uptime;system performance and clinical feasibility were evaluated by the frequencies of risk actions and accidental dislodgement of medical supplies(ADMS).Results All 80 participants completed the intervention,with 40 patients in each group.The baseline characteristics and median observation time of the two groups were balanced(intervention group:48 h/patient vs.control group:49 h/patient).Compared with the control group,the intervention group showed fewer ADMS(2/40 vs.9/40)and detected more risk actions per 100 h(36 vs.25);all system-detected events had corroborating images with complete concordance on manual review,and all nurse-recorded hand-contact events were accurately captured.Conclusions The study demonstrated that the image recognition-based detection system can function stably in clinical settings,providing accurate and continuous surveillance while supporting the early detection of risk actions.By reducing the observation burden and offering real-time cognitive support,the system complements routine nursing care and serves as an additional safety measure in ICU practice.With further optimization and larger multicenter validation,this approach could have the potential to make a significant contribution to the development of smart ICUs and the broader digital transformation of nursing care.
基金supported by Natural Science Foundation of Shandong ProvinceChina[ZR2022MH115]the National Natural Science Foundation of China[81301479,82202593]。
文摘Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.
基金National Natural Science Foundation of China(No.82074396)China Academy of Traditional Chinese Medicine Science and Technology Innovation Project(CI2021A05011)+3 种基金China Academy of Traditional Chinese Medicine Science and Technology Innovation Project(CI2021B017-05)China Academy of Traditional Chinese Medicine Guang'anmen Hospital Renewal of Talent Program for Young Top Talent Training Project,Xinjiang Uygur Autonomous Region(XUAR)Regional Collaborative Innovation Special Project(Shanghai Cooperation Organization Science and Technology Partnership Program and International Science and Technology Cooperation Program)"Research on International Scientific and Technological Cooperation and Services for Overseas Registration and Clinical Use of Ethnic Medicines(2022E01001)".
文摘Infections with the coronavirus disease 2019(COVID-19)and disorders of the heart and blood vessels are causally related.To ascertain the causal relationship between COVID-19 and cardiovascular disease(CVD),we carried out a Mendelian randomization(MR)study through a method known as inverse variance weighting(IVW).When analyzing multiple SNPs,MR can meta-aggregate the effects of multiple loci by using IVW meta-pooling method.The weighted median(WM)is the median of the distribution function obtained by ranking all individual SNP effect values according to their weights.WM yields robust estimates when at least 50%of the information originates from valid instrumental variables(IVs).Directed gene pleiotropy in the included IVs is permitted because MR–Egger does not require a regression straight line through the origin.For MR estimation,IVW,WM and MR-Egger were employed.Sensitivity analysis was conducted using funnel plots,Cochran's Q test,MR–Egger intercept test,MR–PRESSO,and leave-one-out analysis.SNPs related to exposure to COVID-19 and CVD were compiled.CVD for COVID-19 infection,COVID-19 laboratory/self-reported negative,and other very severe respiratory diagnosis and population were randomly assigned using MR.The COVID-19 laboratory/self-reported negative results and other very severe respiratory confirmed cases versus MR analysis of CVD in the population(p>0.05);COVID-19 infection to CVD(p?0.033,OR?1.001,95%CI:1.000–1.001);and the MR–Egger results indicated that COVID-19 infection was associated with CVD risk.This MR study provides preliminary evidence for the validity of the causal link between COVID-19 infection and CVD.
基金supported by the National Natural Science Foundation of China(82322059)the Chinese Academy of Medical·Sciences Innovation Fund for Medical Sciences(2021-I2M-1-010)+1 种基金the National Key Research and Development Program of China(2021YFC2500500)the National High Level Hospital Clinical Research Funding(2023-GSPRC-19).
文摘Objective Observational studies have shown inconsistent associations of loneliness or social isolation(SI)with ischemic heart disease(IHD),with unknown mediators.Methods Using data from genome-wide association studies of predominantly European ancestry,we performed a bidirectional two-sample Mendelian Randomization(MR)study to estimate causal effects of loneliness(N=487,647)and SI traits on IHD(N=184,305).SI traits included whether individuals lived alone,participated in various types of social activities,and how often they had contact with friends or family(N=459,830 to 461,369).A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators,including metabolic,behavioral and psychological factors.Results Loneliness increased IHD risk(OR=2.129;95%confidence interval[CI]:1.380 to 3.285),mediated by body fat percentage,waist-hip ratio,total cholesterol,and low-density lipoprotein cholesterol.For SI traits,only fewer social activities increased IHD risk(OR=1.815;95%CI:1.189 to 2.772),mediated by hypertension,high-density lipoprotein cholesterol,triglycerides,fasting insulin,and smoking cessation.No reverse causality of IHD with loneliness and SI was found.Conclusion These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD,with several mediators as prioritized targets for intervention.
基金funded by the National Natural Science Foundation of China(No.82273704)Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0501400-2023ZD0501402)+4 种基金Beijing Hospitals Authority’s Ascent Plan(DFL20241102)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(No.ZLRK202325)China Postdoctoral Science Foundation(2024M760152)Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development(No.BMU2022XKQ004)Science Foundation of Peking University Cancer Hospital(Nos.BJCH2024BJ02,XKFZ2410,BJCH2025CZ04,and 2022-27)。
文摘Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether key metabolite levels modified the GC primary prevention effects.Methods:Plasma metabolites associated with GC risk were identified through a case-control study.Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial(SIT),a nested case-control study of the Mass Intervention Trial in Linqu,Shandong province(MITS),China,the UK Biobank,and the Finn Gen project.Results:A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population(SIT:HR=1.26 per 1 SD change,95%CI:1.07±1.49;MITS:HR=1.07,95%CI:1.00±1.14)and an increased gastric adenocarcinoma risk in Finn Gen(OR=1.68,95%CI:1.16±2.45).Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level(P-interaction=0.098)and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level(P-interaction=0.02).Conclusions:Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention.Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.
文摘Objective Vitamin deficiencies,particularly in vitamins A,B12,and D,are prevalent across populations and contribute significantly to a range of health issues.While these deficiencies are well documented,the underlying etiology remains complex.Recent studies suggest a close link between the gut microbiota and the synthesis,absorption,and metabolism of these vitamins.However,the specific causal relationships between the gut microbiota composition and vitamin deficiencies remain poorly understood.Identifying key bacterial species and understanding their role in vitamin metabolism could provide critical insights for targeted interventions.Methods We conducted a two-sample Mendelian randomization(MR)study to assess the causal relationship between the gut microbiota and vitamin deficiencies(A,B12,D).The genome-wide association study data for vitamin deficiencies were sourced from the FinnGen biobank,and the gut microbiota data were from the MiBioGen consortium.MR analyses included inverse variance-weighted(IVW),MR‒Egger,weighted median,and weighted mode approaches.Sensitivity analyses and reverse causality assessments were performed to ensure robustness and validate the findings.Results After FDR adjustment,vitamin B12 deficiency was associated with the class Verrucomicrobiae,order Verrucomicrobiales,family Verrucomicrobiaceae,and genus Akkermansia.Vitamin A deficiency was associated with the phylum Firmicutes and the genera Fusicatenibacter and Ruminiclostridium 6.Additional associations for vitamin B12 deficiency included the Enterobacteriaceae and Rhodospirillaceae and the genera Coprococcus 2,Lactococcus,and Ruminococcaceae UCG002.Vitamin D deficiency was associated with the genera Allisonella,Eubacterium,and Tyzzerella 3.Lachnospiraceae and Lactococcus were common risk factors for both B12 and D deficiency.Sensitivity analyses confirmed the robustness of the findings against heterogeneity and horizontal pleiotropy,and reverse MR tests indicated no evidence of reverse causality.Conclusions Our findings reveal a possible causal relationship between specific gut microbiota characteristics and vitamin A,B12 and D deficiencies,providing a theoretical basis for addressing these nutritional deficiencies through the modulation of the gut microbiota in the future and laying the groundwork for related interventions.
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.
文摘Background:Cytomegalovirus(CMV)reactivation is linked to a high mortality rate,especially among the elderly.Prior research suggests that renin-angiotensin system(RAS)inhibitors may influence both the onset and prognosis of pneumonia.This study aims to examine the causal relationship between RAS inhibitor use and the risk of CMV pneumonia using Mendelian randomization(MR)analysis.Methods:We conducted an analysis using data from two genome-wide association studies(GWAS)involving individuals of European ancestry.This dataset included individuals treated with RAS inhibitors and those with CMV pneumonia.We assessed the relationship between RAS inhibitor use and CMV pneumonia risk using the inverse variance weighted(IVW)method.The results were further evaluated for pleiotropy,heterogeneity,and robustness.Results:The Mendelian randomization(MR)analysis revealed a causal relationship between RAS inhibitor use and an increased risk of CMV pneumonia(IVW:odds ratio[OR]=2.73;95%confidence interval[CI]=1.11-6.73;P=0.028).Conclusions:Our finding indicate a positive causal relationship between the use of RAS inhibitors and the onset of CMV pneumonia.
基金supported by the Natural Science Foundation of Hunan Province,China(2024JJ7627).
文摘Objective:Gut microbiota(GM)and blood metabolites are associated with the development of urticaria,yet their specific causal relationships in East Asian populations remain unclear.This study aims to elucidate the causal and mediating relationships among GM,blood metabolites,and urticaria in East Asians using Mendelian randomization(MR)analysis.Methods:Summary-level statistics for 500 GM taxa,112 blood metabolites,and urticaria were obtained from publicly available Genome-Wide Association Studies(GWAS)datasets.Bidirectional MR analyses were performed to examine causal associations among the GM,blood metabolites,and urticaria.The inverse variance weighted(IVW)method served as the primary analytical approach,supplemented by MR-Egger,weighted median,simple mode,and weighted mode methods.Sensitivity analyses included heterogeneity tests,horizontal pleiotropy assessments,and leave-one-out analyses.Mediation analysis was conducted to evaluate the potential mediating effects of blood metabolites on the causal pathways between GM and urticaria.Results:MR analyses identified 12 GM taxa exhibiting significant causal effects on urticaria susceptibility.Nine taxa,such as MF0017_galactose_degradation(OR=1.461,95%CI 1.098 to 1.944,P=0.009),were associated with increased urticaria risk.Three taxa,such as MF0001_arabinoxylan_degradation(OR=0.846,95%CI 0.737 to 0.973,P=0.019),showed protective effects with increased abundance.Additionally,6 blood metabolites demonstrated causal associations with urticaria.Notably,the risk of developing urticaria increases with rising fasting plasma glucose(FPG)levels(OR=1.971,95%CI 1.089 to 3.567,P=0.025).Mediation analysis further demonstrated that FPG partially mediated the protective effect of MF0001_arabinoxylan_degradation on urticaria,accounting for 11.30%of the total effect.Conclusion:This study has delineated specific GM taxa and blood metabolites that hold causal relevance to urticaria in East Asian populations.Notably,arabinogalactan degradation potentially mitigates urticaria risk via reducing FPG concentrations,offering genetic evidence to support therapeutic strategies targeting GM modulation and glucose regulation.
基金supported by the Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia(Project No.MoE-IF-UJ-R2-22-04220773-1).
文摘Domain randomization is a widely adopted technique in deep reinforcement learning(DRL)to improve agent generalization by exposing policies to diverse environmental conditions.This paper investigates the impact of different reset strategies,normal,non-randomized,and randomized,on agent performance using the Deep Deterministic Policy Gradient(DDPG)and Twin Delayed DDPG(TD3)algorithms within the CarRacing-v2 environment.Two experimental setups were conducted:an extended training regime with DDPG for 1000 steps per episode across 1000 episodes,and a fast execution setup comparing DDPG and TD3 for 30 episodes with 50 steps per episode under constrained computational resources.A step-based reward scaling mechanism was applied under the randomized reset condition to promote broader state exploration.Experimental results showthat randomized resets significantly enhance learning efficiency and generalization,with DDPG demonstrating superior performance across all reset strategies.In particular,DDPG combined with randomized resets achieves the highest smoothed rewards(reaching approximately 15),best stability,and fastest convergence.These differences are statistically significant,as confirmed by t-tests:DDPG outperforms TD3 under randomized(t=−101.91,p<0.0001),normal(t=−21.59,p<0.0001),and non-randomized(t=−62.46,p<0.0001)reset conditions.The findings underscore the critical role of reset strategy and reward shaping in enhancing the robustness and adaptability of DRL agents in continuous control tasks,particularly in environments where computational efficiency and training stability are crucial.
基金Supported by Xi’an Science and Technology Program Project(No.24YXYJ0108)Support Projects of Xi’an Children’s Hospital(No.2024I07).
文摘AIM:To investigate the causal relationship between dietary intake and myopia using Mendelian randomization(MR)analysis.METHODS:Genome-wide association study(GWAS)data from the IEU Open GWAS database were utilized to examine associations between myopia and various dietary factors.MR analysis,incorporating both univariable and multivariable approaches,assessed the impact of food intake on myopia risk through five analytical methods,with inverse variance weighted(IVW)serving as the primary reference.Sensitivity analyses,including heterogeneity assessment,horizontal pleiotropy evaluation,and leave-oneout analysis,were conducted to validate the MR findings.RESULTS:Univariable MR analysis identified a causal link between food intake and myopia.Consumption of breaded fish,canned soup,sweet biscuits,and certain fruits correlated with a lower risk of myopia,whereas intake of low-calorie hot chocolate and cereal was associated with an increased risk.Multivariable MR analysis further confirmed that breaded fish consumption exerted a direct protective effect against myopia,particularly when consumed alongside other dietary components.These findings highlight the intricate interplay between specific dietary factors and myopia development,offering valuable insights for further research.CONCLUSION:MR analysis provides evidence supporting a potential causal relationship between breaded fish intake and myopia,underscoring its relevance in targeted myopia prevention strategies.
