The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide associa...The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide association study(GWAS)summary statistics from European populations,we performed a genome-wide pleiotropic analysis to investigate the shared genetic basis and causal associations between skin and GIT diseases.We observed extensive genetic correlations and overlaps between skin and GIT diseases.A total of 298 pleiotropic loci were identified,75 of which were colocalized,and 61 exhibited pleiotropic effects across multiple trait pairs,including 2p16.1(PUS10),6p21.32(HLA-DRB1),10q21.2(ZNF365),and 19q13.11(SLC7A10).Additionally,five novel loci were identified based on the pleiotropic analysis;among them,the 15q22.2 locus harboring RORA was validated by the latest inflammatory bowel disease GWAS.Gene-based analysis identified 394 unique pleiotropic genes,which were enriched in GSA-associated tissues and the immune system,and protein-protein interaction analysis further revealed that the GPCR-cAMP,chromatin remodeling,JAK-STAT,and HLA-mediated immunity pathways were involved in GSA comorbidity.Notably,the JAK-STAT pathway showed strong potential for drug repurposing,with adalimumab targeting tumor necrosis factor and ustekinumab targeting interleukin-12 subunit beta already being used to treat both skin and GIT diseases.Finally,Mendelian randomization analysis identified five significant causal associations,and subsequent mediation analysis identified three potential microbiota-GIT-skin pathways.Taken together,our study demonstrated that the shared genetic factors between skin and GIT diseases were widely distributed across the genome.These findings will enhance our understanding of the genetic mechanisms underlying GSA comorbidity.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
In this paper,we establish some strong laws of large numbers,which are for nonindependent random variables under the framework of sublinear expectations.One of our main results is for blockwise m-dependent random vari...In this paper,we establish some strong laws of large numbers,which are for nonindependent random variables under the framework of sublinear expectations.One of our main results is for blockwise m-dependent random variables,and another is for sub-orthogonal random variables.Both extend the strong law of large numbers for independent random variables under sublinear expectations to the non-independent case.展开更多
We study a finite number of independent random walks with subexponentially distributed increments and negative drifts.We extend the one-dimensional results to finite and fully general stopping times.Assuming that the ...We study a finite number of independent random walks with subexponentially distributed increments and negative drifts.We extend the one-dimensional results to finite and fully general stopping times.Assuming that the distribution of the lengths of these intervals is relatively light compared to the distribution of the increments of the random walks,we derive the asymptotic tail distribution of the partial maximum sum over the random time interval.展开更多
Titanium-based semiconductors are known for their high chemical stability and suitable band gap widths.However,the conventional experimental screening methods are inefficient due to the wide variety of materials.To sp...Titanium-based semiconductors are known for their high chemical stability and suitable band gap widths.However,the conventional experimental screening methods are inefficient due to the wide variety of materials.To speed up the selection process,this work focuses on interpretable feature learning and band gap prediction for titanium-based semiconductors.First,titanium compounds were selected from the Materials Project database by machine learning,and elemental features were extracted using the Magpie descriptors.Then,principal component analysis(PCA)was applied to reduce the data dimensionality,creating a representative dataset.Meantime,heatmaps and SHAP(SHapley Additive exPlanations)methods were used to demonstrate the influence of key features such as electronegativity,covalent radius,period number,and unit cell volume on the bandgap,understanding the relationship between the material’s properties and performance.After comparing different machine learning models,including Random Forest(RF),Support Vector Machines(SVM),Linear Regression(LR),and Gradient Boosting Regression(GBR),the RF was found to be the most accurate for band gap prediction.Finally,the model performance was improved through parameter tuning,showing high accuracy.These findings provide strong data support and design guidance for the development of materials in fields like photocatalysis and solar cells.展开更多
Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrat...Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.展开更多
Debate over the benefits and harms of icing acute muscle injuries remains unresolved.Some contend that ice is ineffective or even harmful,while others promote cryotherapy as a universal remedy.Centrists,often academic...Debate over the benefits and harms of icing acute muscle injuries remains unresolved.Some contend that ice is ineffective or even harmful,while others promote cryotherapy as a universal remedy.Centrists,often academics,call for more high-quality randomized controlled trials(RCTs)to resolve the issue.This viewpoint reframes the debate around 3 key points:first,although ice produces analgesia,evidence for sustained pain relief,beyond the immediate post-treatment period.展开更多
Introduction.Well-designed,strictly implemented,and fully standardized randomized controlled trials(RCTs)are a prerequisite for developing reliable scientific evidence,which can improve clinical practice,health outcom...Introduction.Well-designed,strictly implemented,and fully standardized randomized controlled trials(RCTs)are a prerequisite for developing reliable scientific evidence,which can improve clinical practice,health outcomes,and ultimately benefit patients.Suboptimal reporting is pervasive in medical research,resulting in biased research records and persistent uncertainty about the quality of available evidence.1,2,3,4 The standardization of research reports has attracted considerable attention.In 1996,the Consolidated Standards of Reporting Trials(CONSORT)was first published to improve the quality of RCTs and enhance the reproducibility of trial methods,results,and inferences.展开更多
The important work of Yu,et al.[1]who presented one of the first randomized controlled trials(RCTs)to directly compare robot-assisted and manual percutaneous coronary intervention(PCI),is commendable;offering importan...The important work of Yu,et al.[1]who presented one of the first randomized controlled trials(RCTs)to directly compare robot-assisted and manual percutaneous coronary intervention(PCI),is commendable;offering important insights into the feasibility and outcomes of this emerging technology.While the analysis is timely,several issues warrant further consideration.展开更多
Classical computation of electronic properties in large-scale materials remains challenging.Quantum computation has the potential to offer advantages in memory footprint and computational scaling.However,general and v...Classical computation of electronic properties in large-scale materials remains challenging.Quantum computation has the potential to offer advantages in memory footprint and computational scaling.However,general and viable quantum algorithms for simulating large-scale materials are still limited.We propose and implement random-state quantum algorithms to calculate electronic-structure properties of real materials.Using a random state circuit on a small number of qubits,we employ real-time evolution with first-order Trotter decomposition and Hadamard test to obtain electronic density of states,and we develop a modified quantum phase estimation algorithm to calculate real-space local density of states via direct quantum measurements.Furthermore,we validate these algorithms by numerically computing the density of states and spatial distributions of electronic states in graphene,twisted bilayer graphene quasicrystals,and fractal lattices,covering system sizes from hundreds to thousands of atoms.Our results manifest that the random-state quantum algorithms provide a general and qubit-efficient route to scalable simulations of electronic properties in large-scale periodic and aperiodic materials.展开更多
Both large-scale prospective randomized controlled trials(RCTs)and smaller investigator-initiated trials are essential for evaluating the efficacy and safety of medical interventions.Robust protocols and statistical d...Both large-scale prospective randomized controlled trials(RCTs)and smaller investigator-initiated trials are essential for evaluating the efficacy and safety of medical interventions.Robust protocols and statistical designs ensure the reliability of trial outcomes and improve the credibility of research findings.By reviewing the statistical approaches used in the TORCHLIGHT,NCC2167,and NeoTENNIS trials,this article illustrates the principles underlying large-sample confirmatory RCTs,small-sample exploratory adaptive designs,and single-arm two-stage designs.This discussion is aimed at helping researchers apply these design methods more effectively,to increase the likelihood of success in clinical studies.展开更多
In this paper,we propose a random access scheme termed sign-compute diversity slotted ALOHA(SCDSA).The SCDSA scheme combines diversity transmission with compute-and-forward.Without considering the capture effect and m...In this paper,we propose a random access scheme termed sign-compute diversity slotted ALOHA(SCDSA).The SCDSA scheme combines diversity transmission with compute-and-forward.Without considering the capture effect and multiple user detection techniques,our scheme can reach a high throughput of 0.98 without feedback under finite frame size settings,where the upper bound on performance is 1.Moreover,a lower bound on throughput performance is derived,which is tight in some parameter settings and can be used to approximate theoretical performance.Simulation results validate our analysis and confirm the advantages of our proposed scheme.展开更多
AIM:To clarify the clinical correlations and causal relationships between lipid metabolism and the progression of thyroid-associated ophthalmopathy(TAO).METHODS:This case-control study retrieved clinical data from 201...AIM:To clarify the clinical correlations and causal relationships between lipid metabolism and the progression of thyroid-associated ophthalmopathy(TAO).METHODS:This case-control study retrieved clinical data from 2018 to 2023.A total of 2591 patients were enrolled,including 197 patients with TAO(case group)and 2394 patients with hyperthyroidism without TAO(control group).Serum lipid parameters,including triglycerides,total cholesterol,high-density lipoprotein(HDL),low-density lipoprotein(LDL),and the HDL/total cholesterol ratio,as well as thyroid function markers,were compared between the two groups.Correlation analyses were performed to evaluate the associations between serum lipid levels and key ocular manifestations of TAO,including exophthalmos degree,clinical activity score,and disease severity.Furthermore,Mendelian randomization(MR)analysis was conducted using genome-wide association study(GWAS)datasets,with hyperthyroidism as the exposure variable and serum lipid parameters as the outcome variables,to infer the causal relationship between hyperthyroidism,lipid metabolism,and TAO progression.RESULTS:The TAO group consisted of 101 males and 96 females,while the hyperthyroidism group included 706 males and 1688 females.Compared with the control group,patients with TAO had significantly higher levels of triglycerides(1.83±1.21 vs 1.40±1.08 mmol/L,P<0.01),total cholesterol,LDL,and HDL.Correlation analysis showed that triglyceride levels were positively correlated with exophthalmos degree,whereas HDL levels were inversely correlated with exophthalmos degree.No significant associations were found between serum lipid levels and clinical activity score(P>0.1).MR analysis confirmed that hyperthyroidism exerted a causal effect in reducing serum triglycerides[inverse-variance weighting odds ratio(OR)=0.035,95%confidence interval(CI):0.01-0.12]and total cholesterol(OR=0.085,95%CI:0.02-0.34),with no evidence of horizontal pleiotropy(MR-PRESSO P>0.05).CONCLUSION:Elevated serum triglyceride levels are an independent risk factor for TAO severity,especially exophthalmos,and triglyceride metabolism is inversely regulated by thyroid function.展开更多
AIM:To evaluate the efficacy and safety of 3%diquafosol sodium eye drops in children wearing orthokeratology lenses and with dry eye disease(DED)or at risk of DED.METHODS:Randomized controlled trials.Children with DED...AIM:To evaluate the efficacy and safety of 3%diquafosol sodium eye drops in children wearing orthokeratology lenses and with dry eye disease(DED)or at risk of DED.METHODS:Randomized controlled trials.Children with DED or at risk of DED were randomly assigned in a 1∶1 ratio to receive either 3%diquafosol sodium eye drops 6 times daily or a blank control at Chongqing Aier Children’s Eye Hospital from November 2023 to November 2024.The primary endpoint was the change in the Dry Eye Questionnaire-5(DEQ-5)score from baseline at 12 wk.Secondary assessments included non-invasive breakup time(NIBUT),tear meniscus height,Schirmer’s test,corneal fluorescein staining score,and axial length.RESULTS:A total of 80 participants(80 eyes)were enrolled(40 in each group),the average age of the participants was 11.11±1.88 years,with 43 females(54%)and 37 males(46%),and all completed the trial.After 12 wk,the DEQ-5 scores for the diquafosol sodium group and the blank control group were 1.88±2.02 and 2.88±2.79,respectively(P=0.079).The diquafosol sodium group demonstrated a significant improvement in DEQ-5 dryness symptom scores(-0.33±0.66 vs.0.05±0.81,P=0.023)and NIBUT(6.18±3.73 vs.-1.09±4.40 s,P<0.001)at 12 wk.Additionally,the diquafosol sodium group showed no axial length elongation,in contrast to the blank control group,which exhibited elongation(0.00±0.08 vs.0.05±0.10 mm,P=0.013).No other significant differences were found in the secondary endpoints.No adverse events occurred during the trial.CONCLUSION:Although no statistically significant improvements were noted in the overall DEQ-5 scores,the 3%diquafosol sodium eye drops significantly improved dryness symptoms and NIBUT when compared to the blank control group.展开更多
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
[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
Although diet and gut microbial composition have been linked to chronic respiratory diseases,these associations remain difficult to interpret because of confounding and reverse causation.The gut-lung axis provides a p...Although diet and gut microbial composition have been linked to chronic respiratory diseases,these associations remain difficult to interpret because of confounding and reverse causation.The gut-lung axis provides a plausible framework for this interaction,yet direct genetic evidence is limited.Using a two-step,two-sample Mendelian randomization(MR)framework,supplemented by multivariable MR(MVMR)to adjust for pleiotropic effects and Benjamini-Hochberg false discovery rate(FDR)correction for multiple testing,we assessed the causal contributions of dietary habits and gut microbial taxa to major chronic respiratory diseases.We identified 22 dietary factors with causal effects on disease risk and 225 microbial taxa that acted as independent risk or protective contributors.Mediation analyses further showed that the effects of 12 dietary habits were transmitted through 32 specific microbial taxa.Notably,genetically predicted pork intake increased the risk of chronic obstructive pulmonary disease(COPD)(OR=10.53,95%CI[8.54,13.00]),an effect partly mediated by elevated abundance of CAG-485 sp002404675.In contrast,bread consumption conferred protection against asthma(OR=0.68,95%CI[0.64,0.72]),whereas this benefit was offset by approximately 45%through a pathway involving reduced Veillonella abundance.Collectively,these findings provide genetic support for the gut-lung axis and demonstrate that the gut microbiome functions as a causal mediator linking diet to chronic respiratory disease risk.However,since this study was based on individuals of European ancestry,caution is warranted when generalizing these causal estimates to non-European populations,such as East Asian groups.This work suggests new opportunities for microbiota-targeted prevention and therapeutic strategies.展开更多
This paper aims to develop a unified Bayesian approach for clustered data analysis when observations are subject to missingness at random.The authors consider a general framework in which the parameters of interest ar...This paper aims to develop a unified Bayesian approach for clustered data analysis when observations are subject to missingness at random.The authors consider a general framework in which the parameters of interest are defined through estimating equations,and the probability of missingness follows a general parametric form.The generalized method of moments framework is employed to derive an optimal combination of inverse-probability-weighted estimating equations for the parameters of interest and score equations for propensity score.Using this framework,the authors develop a quasi-Bayesian analysis for clustered samples with missing values.A unified model selection approach is also proposed to compare models characterized by different moment conditions.The authors systematically evaluate the large-sample properties of the proposed quasi-posterior density with both fixed and shrinking priors and establish the selection consistency of the proposed model selection criterion.The proposed results are valid under very mild conditions and offer significant advantages for parameters defined through non-smooth estimating functions.Extensive numerical studies demonstrate that the proposed method performs exceptionally well in finite samples.展开更多
The characterization of track irregularities is crucial in railway dynamics,as track irregularities are the primary source of internal excitation in railway systems.In this paper,three mathematical models are proposed...The characterization of track irregularities is crucial in railway dynamics,as track irregularities are the primary source of internal excitation in railway systems.In this paper,three mathematical models are proposed to characterize the track irregularities under different circumstances.The first model is a novel explicit track spectrum function,which performs better in reflecting the inherent periodic components of track irregularities than the existing track spectra.On this foundation,the second model,a parameterized track spectrum random model,is proposed to represent the vast measured track irregularities from the probabilistic perspective.Finally,the third model,an imprecise track spectrum interval model based on a neighborhood uniform sampling Bootstrap method,is presented to identify the confidential interval of the track spectra when the track irregularity data are limited.Three examples are illustrated to demonstrate the feasibility of the three track irregularity models in characterizing the track irregularities in different conditions.This research can help capture the railway deformation status and optimize track maintenance strategies.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.32470658)the National Key Research and Development Program of China(Grant Nos.2022YFC2502400 and 2022YFC2502402).
文摘The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide association study(GWAS)summary statistics from European populations,we performed a genome-wide pleiotropic analysis to investigate the shared genetic basis and causal associations between skin and GIT diseases.We observed extensive genetic correlations and overlaps between skin and GIT diseases.A total of 298 pleiotropic loci were identified,75 of which were colocalized,and 61 exhibited pleiotropic effects across multiple trait pairs,including 2p16.1(PUS10),6p21.32(HLA-DRB1),10q21.2(ZNF365),and 19q13.11(SLC7A10).Additionally,five novel loci were identified based on the pleiotropic analysis;among them,the 15q22.2 locus harboring RORA was validated by the latest inflammatory bowel disease GWAS.Gene-based analysis identified 394 unique pleiotropic genes,which were enriched in GSA-associated tissues and the immune system,and protein-protein interaction analysis further revealed that the GPCR-cAMP,chromatin remodeling,JAK-STAT,and HLA-mediated immunity pathways were involved in GSA comorbidity.Notably,the JAK-STAT pathway showed strong potential for drug repurposing,with adalimumab targeting tumor necrosis factor and ustekinumab targeting interleukin-12 subunit beta already being used to treat both skin and GIT diseases.Finally,Mendelian randomization analysis identified five significant causal associations,and subsequent mediation analysis identified three potential microbiota-GIT-skin pathways.Taken together,our study demonstrated that the shared genetic factors between skin and GIT diseases were widely distributed across the genome.These findings will enhance our understanding of the genetic mechanisms underlying GSA comorbidity.
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.
文摘In this paper,we establish some strong laws of large numbers,which are for nonindependent random variables under the framework of sublinear expectations.One of our main results is for blockwise m-dependent random variables,and another is for sub-orthogonal random variables.Both extend the strong law of large numbers for independent random variables under sublinear expectations to the non-independent case.
基金supported by Xinjiang Normal University Outstanding Young Teacher Research Launch Fund Project(Grant No.XJNU202116)。
文摘We study a finite number of independent random walks with subexponentially distributed increments and negative drifts.We extend the one-dimensional results to finite and fully general stopping times.Assuming that the distribution of the lengths of these intervals is relatively light compared to the distribution of the increments of the random walks,we derive the asymptotic tail distribution of the partial maximum sum over the random time interval.
文摘Titanium-based semiconductors are known for their high chemical stability and suitable band gap widths.However,the conventional experimental screening methods are inefficient due to the wide variety of materials.To speed up the selection process,this work focuses on interpretable feature learning and band gap prediction for titanium-based semiconductors.First,titanium compounds were selected from the Materials Project database by machine learning,and elemental features were extracted using the Magpie descriptors.Then,principal component analysis(PCA)was applied to reduce the data dimensionality,creating a representative dataset.Meantime,heatmaps and SHAP(SHapley Additive exPlanations)methods were used to demonstrate the influence of key features such as electronegativity,covalent radius,period number,and unit cell volume on the bandgap,understanding the relationship between the material’s properties and performance.After comparing different machine learning models,including Random Forest(RF),Support Vector Machines(SVM),Linear Regression(LR),and Gradient Boosting Regression(GBR),the RF was found to be the most accurate for band gap prediction.Finally,the model performance was improved through parameter tuning,showing high accuracy.These findings provide strong data support and design guidance for the development of materials in fields like photocatalysis and solar cells.
基金supported by the Natural Science Foundation of Hunan Province (2022JJ30987)the Key Research and Development Project of Hunan Province (2024JK2107),China。
文摘Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.
文摘Debate over the benefits and harms of icing acute muscle injuries remains unresolved.Some contend that ice is ineffective or even harmful,while others promote cryotherapy as a universal remedy.Centrists,often academics,call for more high-quality randomized controlled trials(RCTs)to resolve the issue.This viewpoint reframes the debate around 3 key points:first,although ice produces analgesia,evidence for sustained pain relief,beyond the immediate post-treatment period.
基金supported by the Talent Development Plan for High-level Public Health Technical Personnel Project in Beijing,Beijing Municipal Health Commission[No.XKGG-02-03].
文摘Introduction.Well-designed,strictly implemented,and fully standardized randomized controlled trials(RCTs)are a prerequisite for developing reliable scientific evidence,which can improve clinical practice,health outcomes,and ultimately benefit patients.Suboptimal reporting is pervasive in medical research,resulting in biased research records and persistent uncertainty about the quality of available evidence.1,2,3,4 The standardization of research reports has attracted considerable attention.In 1996,the Consolidated Standards of Reporting Trials(CONSORT)was first published to improve the quality of RCTs and enhance the reproducibility of trial methods,results,and inferences.
文摘The important work of Yu,et al.[1]who presented one of the first randomized controlled trials(RCTs)to directly compare robot-assisted and manual percutaneous coronary intervention(PCI),is commendable;offering important insights into the feasibility and outcomes of this emerging technology.While the analysis is timely,several issues warrant further consideration.
基金supported by the Major Project for the Integration of ScienceEducation and Industry (Grant No.2025ZDZX02)。
文摘Classical computation of electronic properties in large-scale materials remains challenging.Quantum computation has the potential to offer advantages in memory footprint and computational scaling.However,general and viable quantum algorithms for simulating large-scale materials are still limited.We propose and implement random-state quantum algorithms to calculate electronic-structure properties of real materials.Using a random state circuit on a small number of qubits,we employ real-time evolution with first-order Trotter decomposition and Hadamard test to obtain electronic density of states,and we develop a modified quantum phase estimation algorithm to calculate real-space local density of states via direct quantum measurements.Furthermore,we validate these algorithms by numerically computing the density of states and spatial distributions of electronic states in graphene,twisted bilayer graphene quasicrystals,and fractal lattices,covering system sizes from hundreds to thousands of atoms.Our results manifest that the random-state quantum algorithms provide a general and qubit-efficient route to scalable simulations of electronic properties in large-scale periodic and aperiodic materials.
基金supported by a grant from the National Science and Technology Major Project(Grant No.2024ZD0519800).
文摘Both large-scale prospective randomized controlled trials(RCTs)and smaller investigator-initiated trials are essential for evaluating the efficacy and safety of medical interventions.Robust protocols and statistical designs ensure the reliability of trial outcomes and improve the credibility of research findings.By reviewing the statistical approaches used in the TORCHLIGHT,NCC2167,and NeoTENNIS trials,this article illustrates the principles underlying large-sample confirmatory RCTs,small-sample exploratory adaptive designs,and single-arm two-stage designs.This discussion is aimed at helping researchers apply these design methods more effectively,to increase the likelihood of success in clinical studies.
文摘In this paper,we propose a random access scheme termed sign-compute diversity slotted ALOHA(SCDSA).The SCDSA scheme combines diversity transmission with compute-and-forward.Without considering the capture effect and multiple user detection techniques,our scheme can reach a high throughput of 0.98 without feedback under finite frame size settings,where the upper bound on performance is 1.Moreover,a lower bound on throughput performance is derived,which is tight in some parameter settings and can be used to approximate theoretical performance.Simulation results validate our analysis and confirm the advantages of our proposed scheme.
基金Supported by the National Natural Science Foundation of China(No.82371104)the Natural Science Foundation of Hunan Province(No.2023JJ30851).
文摘AIM:To clarify the clinical correlations and causal relationships between lipid metabolism and the progression of thyroid-associated ophthalmopathy(TAO).METHODS:This case-control study retrieved clinical data from 2018 to 2023.A total of 2591 patients were enrolled,including 197 patients with TAO(case group)and 2394 patients with hyperthyroidism without TAO(control group).Serum lipid parameters,including triglycerides,total cholesterol,high-density lipoprotein(HDL),low-density lipoprotein(LDL),and the HDL/total cholesterol ratio,as well as thyroid function markers,were compared between the two groups.Correlation analyses were performed to evaluate the associations between serum lipid levels and key ocular manifestations of TAO,including exophthalmos degree,clinical activity score,and disease severity.Furthermore,Mendelian randomization(MR)analysis was conducted using genome-wide association study(GWAS)datasets,with hyperthyroidism as the exposure variable and serum lipid parameters as the outcome variables,to infer the causal relationship between hyperthyroidism,lipid metabolism,and TAO progression.RESULTS:The TAO group consisted of 101 males and 96 females,while the hyperthyroidism group included 706 males and 1688 females.Compared with the control group,patients with TAO had significantly higher levels of triglycerides(1.83±1.21 vs 1.40±1.08 mmol/L,P<0.01),total cholesterol,LDL,and HDL.Correlation analysis showed that triglyceride levels were positively correlated with exophthalmos degree,whereas HDL levels were inversely correlated with exophthalmos degree.No significant associations were found between serum lipid levels and clinical activity score(P>0.1).MR analysis confirmed that hyperthyroidism exerted a causal effect in reducing serum triglycerides[inverse-variance weighting odds ratio(OR)=0.035,95%confidence interval(CI):0.01-0.12]and total cholesterol(OR=0.085,95%CI:0.02-0.34),with no evidence of horizontal pleiotropy(MR-PRESSO P>0.05).CONCLUSION:Elevated serum triglyceride levels are an independent risk factor for TAO severity,especially exophthalmos,and triglyceride metabolism is inversely regulated by thyroid function.
文摘AIM:To evaluate the efficacy and safety of 3%diquafosol sodium eye drops in children wearing orthokeratology lenses and with dry eye disease(DED)or at risk of DED.METHODS:Randomized controlled trials.Children with DED or at risk of DED were randomly assigned in a 1∶1 ratio to receive either 3%diquafosol sodium eye drops 6 times daily or a blank control at Chongqing Aier Children’s Eye Hospital from November 2023 to November 2024.The primary endpoint was the change in the Dry Eye Questionnaire-5(DEQ-5)score from baseline at 12 wk.Secondary assessments included non-invasive breakup time(NIBUT),tear meniscus height,Schirmer’s test,corneal fluorescein staining score,and axial length.RESULTS:A total of 80 participants(80 eyes)were enrolled(40 in each group),the average age of the participants was 11.11±1.88 years,with 43 females(54%)and 37 males(46%),and all completed the trial.After 12 wk,the DEQ-5 scores for the diquafosol sodium group and the blank control group were 1.88±2.02 and 2.88±2.79,respectively(P=0.079).The diquafosol sodium group demonstrated a significant improvement in DEQ-5 dryness symptom scores(-0.33±0.66 vs.0.05±0.81,P=0.023)and NIBUT(6.18±3.73 vs.-1.09±4.40 s,P<0.001)at 12 wk.Additionally,the diquafosol sodium group showed no axial length elongation,in contrast to the blank control group,which exhibited elongation(0.00±0.08 vs.0.05±0.10 mm,P=0.013).No other significant differences were found in the secondary endpoints.No adverse events occurred during the trial.CONCLUSION:Although no statistically significant improvements were noted in the overall DEQ-5 scores,the 3%diquafosol sodium eye drops significantly improved dryness symptoms and NIBUT when compared to the blank control group.
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.
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Although diet and gut microbial composition have been linked to chronic respiratory diseases,these associations remain difficult to interpret because of confounding and reverse causation.The gut-lung axis provides a plausible framework for this interaction,yet direct genetic evidence is limited.Using a two-step,two-sample Mendelian randomization(MR)framework,supplemented by multivariable MR(MVMR)to adjust for pleiotropic effects and Benjamini-Hochberg false discovery rate(FDR)correction for multiple testing,we assessed the causal contributions of dietary habits and gut microbial taxa to major chronic respiratory diseases.We identified 22 dietary factors with causal effects on disease risk and 225 microbial taxa that acted as independent risk or protective contributors.Mediation analyses further showed that the effects of 12 dietary habits were transmitted through 32 specific microbial taxa.Notably,genetically predicted pork intake increased the risk of chronic obstructive pulmonary disease(COPD)(OR=10.53,95%CI[8.54,13.00]),an effect partly mediated by elevated abundance of CAG-485 sp002404675.In contrast,bread consumption conferred protection against asthma(OR=0.68,95%CI[0.64,0.72]),whereas this benefit was offset by approximately 45%through a pathway involving reduced Veillonella abundance.Collectively,these findings provide genetic support for the gut-lung axis and demonstrate that the gut microbiome functions as a causal mediator linking diet to chronic respiratory disease risk.However,since this study was based on individuals of European ancestry,caution is warranted when generalizing these causal estimates to non-European populations,such as East Asian groups.This work suggests new opportunities for microbiota-targeted prevention and therapeutic strategies.
基金supported by the National Key R&D Program of China under Grant No.2022YFA1003701the National Natural Science Foundation of China under Grant Nos.12331009 and 12071416the Yunnan Fundamental Research Projects under Grant No.202201AV070006。
文摘This paper aims to develop a unified Bayesian approach for clustered data analysis when observations are subject to missingness at random.The authors consider a general framework in which the parameters of interest are defined through estimating equations,and the probability of missingness follows a general parametric form.The generalized method of moments framework is employed to derive an optimal combination of inverse-probability-weighted estimating equations for the parameters of interest and score equations for propensity score.Using this framework,the authors develop a quasi-Bayesian analysis for clustered samples with missing values.A unified model selection approach is also proposed to compare models characterized by different moment conditions.The authors systematically evaluate the large-sample properties of the proposed quasi-posterior density with both fixed and shrinking priors and establish the selection consistency of the proposed model selection criterion.The proposed results are valid under very mild conditions and offer significant advantages for parameters defined through non-smooth estimating functions.Extensive numerical studies demonstrate that the proposed method performs exceptionally well in finite samples.
基金supported by the National Natural Science Foundation of China(Grant No.52208445,52478321,52378468)the Fundamental Research Funds for the Central Universities(Grant No.G2021KY05105)+7 种基金the Basic Research Program of Natural Science in Shaanxi Province(Grant No.2022JQ-369)the Open Foundation of National Engineering Laboratory for High Speed Railway Construction(No.HSR202001)the Youth Talent Support Program Project of Xi’an Association for Science and Technology(Grant No.959202413090)Science and Technology Research and Development Program Project of China railway group limited(Major Special Project,No.:2020-Special-022021-Special-082023-Special-07)Innovation-driven project of Central South University(2023CXQD072)the National Natural Science Foundation of Hunan Province(Grant No.:2022-JJ-20071).
文摘The characterization of track irregularities is crucial in railway dynamics,as track irregularities are the primary source of internal excitation in railway systems.In this paper,three mathematical models are proposed to characterize the track irregularities under different circumstances.The first model is a novel explicit track spectrum function,which performs better in reflecting the inherent periodic components of track irregularities than the existing track spectra.On this foundation,the second model,a parameterized track spectrum random model,is proposed to represent the vast measured track irregularities from the probabilistic perspective.Finally,the third model,an imprecise track spectrum interval model based on a neighborhood uniform sampling Bootstrap method,is presented to identify the confidential interval of the track spectra when the track irregularity data are limited.Three examples are illustrated to demonstrate the feasibility of the three track irregularity models in characterizing the track irregularities in different conditions.This research can help capture the railway deformation status and optimize track maintenance strategies.
