BACKGROUND Gamma-aminobutyric acid type A receptor has long been acknowledged as a key target in the pathophysiology of epilepsy.The GABRA1 and GABRG2 genes encode the α1 and γ2 subunits of the gamma-aminobutyric ac...BACKGROUND Gamma-aminobutyric acid type A receptor has long been acknowledged as a key target in the pathophysiology of epilepsy.The GABRA1 and GABRG2 genes encode the α1 and γ2 subunits of the gamma-aminobutyric acid type A receptor,a key protein implicated in the development of epilepsy.However,the specific association of the GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 polymorphisms with antiepileptic drug resistance has been elucidated in only a limited number of investigations.AIM To elucidate the association between GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 gene mutations and drug resistance in epilepsy patients.METHODS A total of 100 epilepsy patients(50 drug responsive and 50 drug resistant subjects)were recruited and rs2279020-and rs211013-polymorphism analyzed by restriction fragment length polymorphism-polymerase chain reaction technique.RESULTS For GABRA1 rs2279020 polymorphism,AG genotype exhibited risk association with an odds ratio of 0.966(95%confidence interval=0.346-2.698)with P value=0.948;however,this association did not achieve statistical significance(P=0.948).Additionally,a higher risk association was identified with the GG genotype,with an odds ratio of 1.808(P=0.382).GABRG2 rs211013 polymorphism revealed no significant association with drug resistance.CONCLUSION The GABRA1 rs2279020 genetic variation is associated with an increased risk for the AG and GG variants,although this association was not statistically significant.Limited investigations have explored the relevance of genetic variations in epilepsy and drug resistance.Longitudinal research is needed to better understand their significance in epilepsy management and to optimize therapeutic strategies.展开更多
The question of whether an ideal network exists with global scalability in its full life cycle has always been a first-principles problem in the research of network systems and architectures.Thus far,it has not been p...The question of whether an ideal network exists with global scalability in its full life cycle has always been a first-principles problem in the research of network systems and architectures.Thus far,it has not been possible to scientifically practice the design criteria of an ideal network in a unimorphic network system,making it difficult to adapt to known services with clear application scenarios while supporting the ever-growing future services with unexpected characteristics.Here,we theoretically prove that no unimorphic network system can simultaneously meet the scalability requirement in a full cycle in three dimensions—the service-level agreement(S),multiplexity(M),and variousness(V)—which we name as the“impossible SMV triangle”dilemma.It is only by transforming the current network development paradigm that the contradiction between global scalability and a unified network infrastructure can be resolved from the perspectives of thinking,methodology,and practice norms.In this paper,we propose a theoretical framework called the polymorphic network environment(PNE),the first principle of which is to separate or decouple application network systems from the infrastructure environment and,under the given resource conditions,use core technologies such as the elementization of network baselines,the dynamic aggregation of resources,and collaborative software and hardware arrangements to generate the capability of the“network of networks.”This makes it possible to construct an ideal network system that is designed for change and capable of symbiosis and coexistence with the generative network morpha in the spatiotemporal dimensions.An environment test for principle verification shows that the generated representative application network modalities can not only coexist without mutual influence but also independently match well-defined multimedia services or custom services under the constraints of technical and economic indicators.展开更多
BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis th...BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.展开更多
Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wil...Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wild C.oleifera can serve as a case for studying the molecular bases of adaptive evolution to freezing stress.Here,47 wild C.oleifera from 11 natural distribution sites in China and 4 relative species of C.oleifera were selected for genome sequencing.“Min Temperature of Coldest Month”(BIO6)had the highest comprehensive contribution to wild C.oleifera distribution.The population genetic structure of wild C.oleifera could be divided into two groups:in cold winter(BIO6≤0℃)and warm winter(BIO6>0℃)areas.Wild C.oleifera in cold winter areas might have experienced stronger selection pressures and population bottlenecks with lower N_(e) than those in warm winter areas.155 singlenucleotide polymorphisms(SNPs)were significantly correlated with the key bioclimatic variables(106 SNPs significantly correlated with BIO6).Twenty key SNPs and 15 key copy number variation regions(CNVRs)were found with genotype differentiation>50%between the two groups of wild C.oleifera.Key SNPs in cis-regulatory elements might affect the expression of key genes associated with freezing tolerance,and they were also found within a CNVR suggesting interactions between them.Some key CNVRs in the exon regions were closely related to the differentially expressed genes under freezing stress.The findings suggest that rich SNPs and CNVRs in polyploid trees may contribute to the adaptive evolution to freezing stress.展开更多
In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology bas...In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology based on the principle of high-throughput sequencing,and established a multi-locus 10 animalderived components identification method of cattle,goat,sheep,donkey,horse,chicken,duck,goose,pigeon,quail in meat and meat products.The specific loci of each species could be detected and the species could be accurately identified,including 5 loci for cattle and duck,3 loci for sheep,9 loci for chicken and horse,10 loci for goose and pigeon,6 loci for quail and 1 locus for donkey and goat,and an adulteration model was established to simulate commercially available samples.The results showed that the method established in this study had high throughput,good repeatability and accuracy,and was able to identify 10 animalderived components simultaneously with 100%repeatability accuracy.The detection limit was 0.1%(m/m)in simulated samples of chicken,duck and horse.Using the method established in this study to test commercially available samples,4 samples from 14 commercially available samples were detected to be inconsistent with the labels,of which 2 did not contain the target ingredient and 2 were adulterated with small amounts of other ingredients.展开更多
BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associat...BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associated with reduced DPD enzyme activity.AIM To assess the prevalence of DPYD polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.METHODS A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts:(1)149 patients who started fluoropyrimidines after DPYD testing;and(2)151 patients treated without DPYD testing.Among the patients in cohort A,15%tested only the DPYD2A polymorphism,19%tested four polymorphisms(DPYD2A,HapB3,c.2846A>T,and DPYD13),and 66%tested five polymorphisms including DPYD6.RESULTS Overall,14.8%of patients were found to be carriers of a DPYD variant,the most common being DPYD6(12.1%).Patients in cohort A reported≥G3 toxicities(P=0.00098),particularly fewer nonhematological toxicities(P=0.0028)compared with cohort B,whereas there was no statistically significant difference between the two cohorts in hematological toxicities(P=0.6944).Significantly fewer chemotherapy dose reductions(P=0.00002)were observed in cohort A compared to cohort B,whereas there was no statistically significant differences in chemotherapy delay.CONCLUSION Although this study had a limited sample size,it provides additional information on the prevalence of DPYD polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.展开更多
[ Objective] The relationship between the genetic evolution and phylogenesis of the main grasshopper species in Inner Mongolia grasslands in molecular level was studied. [ Method] Random amplified polymorphic DNA （R...[ Objective] The relationship between the genetic evolution and phylogenesis of the main grasshopper species in Inner Mongolia grasslands in molecular level was studied. [ Method] Random amplified polymorphic DNA （RAPD） technique was used to amplify the 80 individuals of 8 grasshoppers （4 families, 6 genera） in Acridoidea, the polymorphisms of their genomic DNA were compared. [ Result] 64 specific fragments were amplified by 7 primers with the molecular weight of 300 -2 000 bp. The genetic distance between 8 grasshoppers was 0.228 2 -0.589 6. Band pat- tern showed that polymorphism was commonly existed in different genus within the same family and different species within the same genus. The resuits were conducted UPGMA cluster analysis according to Neis＇ genetic distance, the results showed that the species within the same genus first clustered together, then the species in the same family clustered together. [ Condusloa] The study could provide molecular biological basis for system development and evolution research of main grasshoppers in Inner Mongolia grassland.展开更多
Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damag...Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.展开更多
Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was cond...Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.展开更多
Heterogeneous graphs generally refer to graphs with different types of nodes and edges.A common approach for extracting useful information from heterogeneous graphs is to use meta-graphs,which can be seen as a special...Heterogeneous graphs generally refer to graphs with different types of nodes and edges.A common approach for extracting useful information from heterogeneous graphs is to use meta-graphs,which can be seen as a special kind of directed acyclic graph with same node and edge types as the heterogeneous graph.However,how to design proper metagraphs is challenging.Recently,there have been many works on learning suitable metagraphs from a heterogeneous graph.Existing methods generally introduce continuous weights for edges that are independent of each other,which ignores the topological structures of meta-graphs and can be ineffective.To address this issue,the authors propose a new viewpoint from tensor on learning meta-graphs.Such a viewpoint not only helps interpret the limitation of existing works by CANDECOMP/PARAFAC(CP)decomposition,but also inspires us to propose a topology-aware tensor decomposition,called TENSUS,that reflects the structure of DAGs.The proposed topology-aware tensor decomposition is easy to use and simple to implement,and it can be taken as a plug-in part to upgrade many existing works,including node classification and recommendation on heterogeneous graphs.Experimental results on different tasks demonstrate that the proposed method can significantly improve the state-of-the-arts for all these tasks.展开更多
Two landmark studies demonstrate synergistic approaches to gastrointestinal cancer management.Lin et al identified activin A receptor type 1C polymor-phisms(rs4556933/rs77886248)as esophageal squamous cell carcinoma r...Two landmark studies demonstrate synergistic approaches to gastrointestinal cancer management.Lin et al identified activin A receptor type 1C polymor-phisms(rs4556933/rs77886248)as esophageal squamous cell carcinoma risk modifiers in Chinese Han populations through a case-control study(1264 patients/1361 controls),revealing transforming growth factor-beta pathway-mediated susceptibility in older male smokers(P<0.001).Concurrently,Luo et al established imaging-based differentiation of pancreatic cancer subtypes(pancreatic ductal adenocarcinoma vs neuroendocrine tumors)via retrospective analysis of 500 cases(area under the curve=0.89),enabling earlier intervention.These findings underscore the transformative potential of combining genetic risk stratification with advanced imaging to guide precision screening and therapeutic strategies,addressing critical gaps in esophageal and pancreatic cancer outcomes.展开更多
In our work,polymorphism strategy has been successfully applied to tune up chromism and luminescence properties of viologen-based materials.Two polymorphs of viologen-based complexes ofα-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2...In our work,polymorphism strategy has been successfully applied to tune up chromism and luminescence properties of viologen-based materials.Two polymorphs of viologen-based complexes ofα-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2)(1)andβ-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2)(2)(PHSQ=N-(4-sulfophenyl)-4,4-bipyridinium)were synthesized by changing the solvent.They can both respond to UV light and electricity in the manner of chromism visible to the naked eye and the coloration states have good reversibility,through which an inkless erasable printing model has been established.But the coloration contrast of 1 is higher compared to 2.Meanwhile,they both exhibit photoluminescence properties and the intensity of 1 is twice that of 2,which is accompanied by photoquenching upon continuous UV light irradiation.The only divergence of disordered/ordered O atoms in the two crystalline compounds leads to significantly different chromic and luminescent properties.Further explorations simultaneously demonstrate that the different chromic performance between 1 and 2 should attribute to the alteration of stimulus-induced(light/electricity)electron transfer channels caused by the ordered/disordered O atoms in the complexes,which is achieved through C-H···O and O-H···O interactions to change crystal arrangement and structural rigidity,thus affect luminescent properties.展开更多
Objective:Neuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings.Previous genome-wide association studies(GWASs)have identified many loci associated with neuroblast...Objective:Neuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings.Previous genome-wide association studies(GWASs)have identified many loci associated with neuroblastoma susceptibility;however,their application in risk prediction for Chinese children has not been systematically explored.This study seeks to enhance neuroblastoma risk prediction by validating these loci and evaluating their performance in polygenic risk models.Methods:We validated 35 GWAS-identified neuroblastoma susceptibility loci in a cohort of Chinese children,consisting of 402 neuroblastoma patients and 473 healthy controls.Genotyping these polymorphisms was conducted via the TaqMan method.Univariable and multivariable logistic regression analyses revealed the genetic loci significantly associated with neuroblastoma risk.We constructed polygenic risk models by combining these loci and assessed their predictive performance via area under the curve(AUC)analysis.We also established a polygenic risk scoring(PRS)model for risk prediction by adopting the PLINK method.Results:Fourteen loci,including ten protective polymorphisms from CASC15,BARD1,LMO1,HSD17B12,and HACE1,and four risk variants from BARD1,RSRC1,CPZ and MMP20 were significantly associated with neuroblastoma risk.Compared with single-gene model,the 8-gene model(AUC=0.72)and 13-gene model(AUC=0.73)demonstrated superior predictive performance.Additionally,a PRS incorporating six significant loci achieved an AUC of 0.66,effectively stratifying individuals into distinct risk categories regarding neuroblastoma susceptibility.A higher PRS was significantly associated with advanced International Neuroblastoma Staging System(INSS)stages,suggesting its potential for clinical risk stratification.Conclusions:Our findings validate multiple loci as neuroblastoma risk factors in Chinese children and demonstrate the utility of polygenic risk models,particularly the PRS,in improving risk prediction.These results suggest that integrating multiple genetic variants into a PRS can enhance neuroblastoma risk stratification and potentially improve early diagnosis by guiding targeted screening programs for high-risk children.展开更多
Objective:This review examined the co-morbidity of malaria and hypertension in Nigerian adults,with a focus on epidemiological trends,genetic and environmental risk factors,pathophysiological mechanisms,and systemic h...Objective:This review examined the co-morbidity of malaria and hypertension in Nigerian adults,with a focus on epidemiological trends,genetic and environmental risk factors,pathophysiological mechanisms,and systemic healthcare barriers.Methods:A qualitative synthesis of peer-reviewed literature,national health surveys,and institutional reports published between 2000 and 2025 was conducted using thematic analysis.While centered on Nigeria,the review incorporated comparative insights from global studies on renin angiotensin aldosterone system polymorphisms,co-infection dynamics,and health service inequalities.Results:The findings indicate overlapping risk factors including renin angiotensin aldosterone system gene polymorphisms,urbanization,and poverty.Angiotensin Ⅱ demonstrates dual functions,contributing both to malaria suppression and to hypertension pathogenesis.Clinical challenges include diagnostic overlap,adverse drug interactions,and disparities in service delivery between rural and urban populations.These challenges particularly affect older adults and highlight systemic gaps in access,workforce distribution,and policy alignment.Conclusion:The dual burden of malaria and hypertension in Nigeria requires integrated disease management strategies that address both communicable and non-communicable disease risks.Urgent priorities include multisectoral policy reforms,expanded rural health investments,and the adoption of precision medicine approaches guided by genetic profiling.The implications extend to clinical practice through co-screening and tailored treatment protocols and to public health policy,where integrated frameworks are essential to reducing inequities and improving long-term outcomes.展开更多
The amalgamation of herbal medicine and nanoformulation technology presents a compelling avenue for the advancement of pharmaceutical and health food products.This synergy capitalizes on the inherent therapeutic prope...The amalgamation of herbal medicine and nanoformulation technology presents a compelling avenue for the advancement of pharmaceutical and health food products.This synergy capitalizes on the inherent therapeutic properties of herbal extracts while harnessing the innovative capabilities of nano-scale formulation.Nano-technology has revolutionized drug delivery systems,offering enhanced bioavailability and targeted delivery of active compounds.The global research landscape reflects a burgeoning interest in nano-based pharmaceuticals,driven by their potential to overcome traditional limitations and optimize therapeutic outcomes.Vietnam,with its rich biodiversity and burgeoning nano-industry,stands at the forefront of this convergence.Vietlife,a prominent player in health product research and manufacturing,is poised to capitalize on this convergence.By leveraging indigenous herbal knowledge and cutting-edge nanoformulation techniques,Vietlife can pioneer the development of novel pharmaceutical and health food solutions.In conclusion,the integration of herbal medicine and nanoformulation technology opens up promising opportunities for the development of pharmaceuticals and healthcare products.Vietnam and Vietlife can capitalize on this trend to drive sustainable development and establish their presence in the international market.展开更多
Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism.Its genetic polymorphisms affect the metabolism of methyl donors,including folate and betaine,and are consequently associated with the dev...Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism.Its genetic polymorphisms affect the metabolism of methyl donors,including folate and betaine,and are consequently associated with the development of various chronic diseases such as stroke and neoplasms.Methods This umbrella review,covering the period from 2006 to 2025,searched PubMed,Embase,Web of Science,Medline,CNKI,WanFang,and Cochrane Library databases for published systematic reviews and meta-analyses of polymorphisms relating to the MTHFR C677T and A1298C gene polymorphisms and various chronic diseases.Subsequently,this study assessed methodological quality with AMSTAR-2,while the strength of evidence for each outcome was graded according to the GRADE and the credibility evaluation.This umbrella review included 39 studies related to 8 diseases classified according to the ICD-10 classification.Results Overall,C677T exhibited a positive correlation with depression(allele:OR=1.18,95%CI:1.13-1.24;dominant:OR=1.16,95%CI:1.09-1.23;recessive:OR=1.42,95%CI:1.30-1.56;homozygote:OR=1.48,95%CI:1.34-1.63),and polycystic ovary syndrome(allele:OR=1.35,95%CI:1.24-1.46;dominant:OR=1.46,95%CI:1.30-1.64;recessive:OR=1.39,95%CI:1.19-1.62;homozygote:OR=1.63,95%CI:1.38-1.93),and exhibited a negative correlation with oral cancer(allele:OR=0.24,95%CI:0.22-0.26;dominant:OR=0.14,95%CI:0.12-0.16;recessive:OR=0.31,95%CI:0.28-0.35;homozygote:OR=0.14,95%CI:0.12-0.16).A1298C was positively associated with polycystic ovary syndrome in four models(allele:OR=1.93,95%CI:1.67-2.21;dominant:OR=1.93,95%CI:1.64-2.27;recessive:OR=3.72,95%CI:2.47-5.61;homozygote:OR=4.38,95%CI:2.90-6.62).Conclusion The MTHFR C677T and A1298C gene polymorphisms demonstrated significant associations with non-communicable diseases,thereby contributing to the advancement of precision medicine.展开更多
Hypertension(HT)is a major risk factor for cardiovascular diseases.Krüppel-like factors(KLFs)are important transcription factors in eukaryotes.Studies have reported that KLF4 and KLF5 are correlated with several ...Hypertension(HT)is a major risk factor for cardiovascular diseases.Krüppel-like factors(KLFs)are important transcription factors in eukaryotes.Studies have reported that KLF4 and KLF5 are correlated with several cardiovascular diseases,but population-based studies on associations between HT and KLF4 or KLF5 have rarely been reported.Therefore,the current study investigated the associations of genetic variants and m RNA expression levels of KLF4 and KLF5 with HT,as well as the effects of antihypertensive drugs on the expression levels of these genes.The associations of one single-nucleotide polymorphism(SNP)in KLF4 and three SNPs in KLF5with HT were analyzed using a combination of case-control and cohort studies.The study populations were selected from a community-based cohort in four regions of Jiangsu province.The risks of HT were estimated through logistic and Cox regression analyses.In addition,m RNA expression levels of KLF4 and KLF5 were detected in 246 controls and 385 HT cases selected from the aforementioned cohort.Among the HT cases,263were not taking antihypertensive drugs[AHD(-)]and 122 were taking antihypertensive drugs[AHD(+)].In the case-control study,SNP rs9573096(C>T)in KLF5 was significantly associated with an increased risk of HT in the additive model(adjusted odds ratio[OR],1.106;95%confidence interval[CI],1.009 to 1.212).In the cohort study of the normotensive population,rs9573096 in KLF5 was also significantly associated with an increased risk of HT in the additive model(adjusted hazards ratio[HR],1.199;95%CI,1.070 to 1.344).KLF4 and KLF5m RNA expression levels were significantly higher in the AHD(-)group than in the control group(P<0.05),but lower in the AHD(+)group than in the AHD(-)group(P<0.05).The current study demonstrated the associations of KLF4 and KLF5 genetic variants with hypertension,as well as the association of the indicative variations in m RNA expression levels of KLF4 and KLF5 with the risk of hypertension and antihypertensive treatment.展开更多
BACKGROUND The NaV1.1 sodium channel alpha subunit,encoded by SCN1A,is crucial for initiating and propagating action potentials in neurons.SCN1A gene has long been an established target in the etiology and therapy of ...BACKGROUND The NaV1.1 sodium channel alpha subunit,encoded by SCN1A,is crucial for initiating and propagating action potentials in neurons.SCN1A gene has long been an established target in the etiology and therapy of epilepsy.However,very few studies have investigated the relevance of genetic variations in epilepsy and anti-epileptic drug resistance.AIM To investigate associations between polymorphisms,rs121917953 T/A and rs121918623 C/T,and drug resistance in epilepsy patients in the north Indian population.METHODS A total of 100 age-and sex-matched epilepsy patients(50 drug responsive and 50 drug resistant subjects)were recruited and SCN1A rs121918623 C/T*and rs121917953 T/A*polymorphisms were analyzed by the allele specific-PCR technique.χ^(2)and Fisher’s exact test were used to estimate differences between the distribution of SCN1A rs121918623 and rs121917953 gene polymorphisms among various groups.The association between distinct rs121917953 genotypes and drug resistance was analyzed using logistic regression analysis.RESULTS For the SCN1A rs121917953 T/A*(D188V)polymorphism,a significantly higher proportion of individuals with AT genotype were observed in the drug-resistant group as compared to the drug-responsive group.Additionally,a higher risk association was exhibited by AT genotype for drug resistance with an odds ratio of 3.51 and P value=0.017.For the SCN1A rs121918623 C/T*(T875M)polymorphism,no significant difference in genotype distribution was observed between the drug-resistant and drug-sensitive groups.CONCLUSION Our findings indicate that the SCN1A polymorphism D188V is associated with a higher risk of drug resistance for the AT variant as compared to the homozygous TT wild-type.Further research is needed at the functional level and in larger cohorts to determine the potential of these genes as a therapeutic target in epilepsy subjects.展开更多
BACKGROUND There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus(GDM),and the correlation between genetic factors related to folic acid metabolism pathways and...BACKGROUND There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus(GDM),and the correlation between genetic factors related to folic acid metabolism pathways and GDM remains to be revealed.AIM To examine the association between single-nucleotide polymorphisms(SNPs)of enzyme genes in the folate metabolite pathway as well as that between GDM-related genes and risk for GDM.METHODS A nested case-control study was conducted with GDM cases(n=412)and healthy controls(n=412).DNA was extracted blood samples and SNPs were genotyped using Agena Bioscience’s MassARRAY gene mass spectrometry system.The associations between different SNPs of genes and the risk for GDM were estimated using logistic regression models.The generalized multi-factor dimensionality reduction(GMDR)method was used to analyze gene-gene and gene-environment interactions using the GMDR 0.9 software.RESULTS The variation allele frequency of melatonin receptor 1B(MTNR1B)rs10830963 was higher in the GDM group than in controls(P<0.05).MTNR1B rs10830963 mutant G was associated with risk for GDM[adjusted odds ratio(aOR):1.43;95%confidence interval(95%CI):1.13-1.80]in the additive model.MTNR1B rs10830963 GG+GC was significantly associated with the risk for GDM(aOR:1.65;95%CI:1.23-2.22)in the dominant model.The two-locus model of MTNR1B rs10830963 and CHEMERIN rs4721 was the best model(P<0.05)for gene-gene interactions in the GMDR results.The high-risk rs10830963×rs4721 type of interaction was a risk factor for GDM(aOR:2.09;95%CI:1.49-2.93).CONCLUSION This study does not find an association between SNPs of folate metabolic enzymes and risk for GDM.The G mutant allele of MTNR1B rs10830963 is identified as a risk factor for GDM in the additive model,and there may be gene-gene interactions between MTNR1B rs10830963 and CHEMERIN rs4721.It is conducive to studying the causes of GDM and provides a new perspective for the precise prevention of this disease.展开更多
文摘BACKGROUND Gamma-aminobutyric acid type A receptor has long been acknowledged as a key target in the pathophysiology of epilepsy.The GABRA1 and GABRG2 genes encode the α1 and γ2 subunits of the gamma-aminobutyric acid type A receptor,a key protein implicated in the development of epilepsy.However,the specific association of the GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 polymorphisms with antiepileptic drug resistance has been elucidated in only a limited number of investigations.AIM To elucidate the association between GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 gene mutations and drug resistance in epilepsy patients.METHODS A total of 100 epilepsy patients(50 drug responsive and 50 drug resistant subjects)were recruited and rs2279020-and rs211013-polymorphism analyzed by restriction fragment length polymorphism-polymerase chain reaction technique.RESULTS For GABRA1 rs2279020 polymorphism,AG genotype exhibited risk association with an odds ratio of 0.966(95%confidence interval=0.346-2.698)with P value=0.948;however,this association did not achieve statistical significance(P=0.948).Additionally,a higher risk association was identified with the GG genotype,with an odds ratio of 1.808(P=0.382).GABRG2 rs211013 polymorphism revealed no significant association with drug resistance.CONCLUSION The GABRA1 rs2279020 genetic variation is associated with an increased risk for the AG and GG variants,although this association was not statistically significant.Limited investigations have explored the relevance of genetic variations in epilepsy and drug resistance.Longitudinal research is needed to better understand their significance in epilepsy management and to optimize therapeutic strategies.
基金supported by the National Key Research and Development Program of China(2022YFB2901403)the Songshan Laboratory Project(221100210900-02).
文摘The question of whether an ideal network exists with global scalability in its full life cycle has always been a first-principles problem in the research of network systems and architectures.Thus far,it has not been possible to scientifically practice the design criteria of an ideal network in a unimorphic network system,making it difficult to adapt to known services with clear application scenarios while supporting the ever-growing future services with unexpected characteristics.Here,we theoretically prove that no unimorphic network system can simultaneously meet the scalability requirement in a full cycle in three dimensions—the service-level agreement(S),multiplexity(M),and variousness(V)—which we name as the“impossible SMV triangle”dilemma.It is only by transforming the current network development paradigm that the contradiction between global scalability and a unified network infrastructure can be resolved from the perspectives of thinking,methodology,and practice norms.In this paper,we propose a theoretical framework called the polymorphic network environment(PNE),the first principle of which is to separate or decouple application network systems from the infrastructure environment and,under the given resource conditions,use core technologies such as the elementization of network baselines,the dynamic aggregation of resources,and collaborative software and hardware arrangements to generate the capability of the“network of networks.”This makes it possible to construct an ideal network system that is designed for change and capable of symbiosis and coexistence with the generative network morpha in the spatiotemporal dimensions.An environment test for principle verification shows that the generated representative application network modalities can not only coexist without mutual influence but also independently match well-defined multimedia services or custom services under the constraints of technical and economic indicators.
基金Supported by The National Natural Science Foundation of China,No.82350127 and No.82241013the Shanghai Natural Science Foundation,No.20ZR1411600+2 种基金the Shanghai Shenkang Hospital Development Center,No.SHDC2020CR4039the Bethune Ethicon Excellent Surgery Foundation,No.CESS2021TC04Xuhui District Medical Research Project of Shanghai,No.SHXH201805.
文摘BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.
基金funded by the National Natural Science Foundation of China(grant no.32270238 and 31870311).
文摘Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wild C.oleifera can serve as a case for studying the molecular bases of adaptive evolution to freezing stress.Here,47 wild C.oleifera from 11 natural distribution sites in China and 4 relative species of C.oleifera were selected for genome sequencing.“Min Temperature of Coldest Month”(BIO6)had the highest comprehensive contribution to wild C.oleifera distribution.The population genetic structure of wild C.oleifera could be divided into two groups:in cold winter(BIO6≤0℃)and warm winter(BIO6>0℃)areas.Wild C.oleifera in cold winter areas might have experienced stronger selection pressures and population bottlenecks with lower N_(e) than those in warm winter areas.155 singlenucleotide polymorphisms(SNPs)were significantly correlated with the key bioclimatic variables(106 SNPs significantly correlated with BIO6).Twenty key SNPs and 15 key copy number variation regions(CNVRs)were found with genotype differentiation>50%between the two groups of wild C.oleifera.Key SNPs in cis-regulatory elements might affect the expression of key genes associated with freezing tolerance,and they were also found within a CNVR suggesting interactions between them.Some key CNVRs in the exon regions were closely related to the differentially expressed genes under freezing stress.The findings suggest that rich SNPs and CNVRs in polyploid trees may contribute to the adaptive evolution to freezing stress.
基金financially supported by National Key R&D Program(2021YFF0701905)。
文摘In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology based on the principle of high-throughput sequencing,and established a multi-locus 10 animalderived components identification method of cattle,goat,sheep,donkey,horse,chicken,duck,goose,pigeon,quail in meat and meat products.The specific loci of each species could be detected and the species could be accurately identified,including 5 loci for cattle and duck,3 loci for sheep,9 loci for chicken and horse,10 loci for goose and pigeon,6 loci for quail and 1 locus for donkey and goat,and an adulteration model was established to simulate commercially available samples.The results showed that the method established in this study had high throughput,good repeatability and accuracy,and was able to identify 10 animalderived components simultaneously with 100%repeatability accuracy.The detection limit was 0.1%(m/m)in simulated samples of chicken,duck and horse.Using the method established in this study to test commercially available samples,4 samples from 14 commercially available samples were detected to be inconsistent with the labels,of which 2 did not contain the target ingredient and 2 were adulterated with small amounts of other ingredients.
文摘BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associated with reduced DPD enzyme activity.AIM To assess the prevalence of DPYD polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.METHODS A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts:(1)149 patients who started fluoropyrimidines after DPYD testing;and(2)151 patients treated without DPYD testing.Among the patients in cohort A,15%tested only the DPYD2A polymorphism,19%tested four polymorphisms(DPYD2A,HapB3,c.2846A>T,and DPYD13),and 66%tested five polymorphisms including DPYD6.RESULTS Overall,14.8%of patients were found to be carriers of a DPYD variant,the most common being DPYD6(12.1%).Patients in cohort A reported≥G3 toxicities(P=0.00098),particularly fewer nonhematological toxicities(P=0.0028)compared with cohort B,whereas there was no statistically significant difference between the two cohorts in hematological toxicities(P=0.6944).Significantly fewer chemotherapy dose reductions(P=0.00002)were observed in cohort A compared to cohort B,whereas there was no statistically significant differences in chemotherapy delay.CONCLUSION Although this study had a limited sample size,it provides additional information on the prevalence of DPYD polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.
基金Supported by Basic Scientific Research Fund Project of Nonprofit Research Institutions(Grassland Research Institute,Chinese Academy of Agricultural Sciences)~~
文摘[ Objective] The relationship between the genetic evolution and phylogenesis of the main grasshopper species in Inner Mongolia grasslands in molecular level was studied. [ Method] Random amplified polymorphic DNA （RAPD） technique was used to amplify the 80 individuals of 8 grasshoppers （4 families, 6 genera） in Acridoidea, the polymorphisms of their genomic DNA were compared. [ Result] 64 specific fragments were amplified by 7 primers with the molecular weight of 300 -2 000 bp. The genetic distance between 8 grasshoppers was 0.228 2 -0.589 6. Band pat- tern showed that polymorphism was commonly existed in different genus within the same family and different species within the same genus. The resuits were conducted UPGMA cluster analysis according to Neis＇ genetic distance, the results showed that the species within the same genus first clustered together, then the species in the same family clustered together. [ Condusloa] The study could provide molecular biological basis for system development and evolution research of main grasshoppers in Inner Mongolia grassland.
文摘Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.
文摘Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.
基金National Key Research and Development Program of China,Grant/Award Number:2023YFB2903904。
文摘Heterogeneous graphs generally refer to graphs with different types of nodes and edges.A common approach for extracting useful information from heterogeneous graphs is to use meta-graphs,which can be seen as a special kind of directed acyclic graph with same node and edge types as the heterogeneous graph.However,how to design proper metagraphs is challenging.Recently,there have been many works on learning suitable metagraphs from a heterogeneous graph.Existing methods generally introduce continuous weights for edges that are independent of each other,which ignores the topological structures of meta-graphs and can be ineffective.To address this issue,the authors propose a new viewpoint from tensor on learning meta-graphs.Such a viewpoint not only helps interpret the limitation of existing works by CANDECOMP/PARAFAC(CP)decomposition,but also inspires us to propose a topology-aware tensor decomposition,called TENSUS,that reflects the structure of DAGs.The proposed topology-aware tensor decomposition is easy to use and simple to implement,and it can be taken as a plug-in part to upgrade many existing works,including node classification and recommendation on heterogeneous graphs.Experimental results on different tasks demonstrate that the proposed method can significantly improve the state-of-the-arts for all these tasks.
文摘Two landmark studies demonstrate synergistic approaches to gastrointestinal cancer management.Lin et al identified activin A receptor type 1C polymor-phisms(rs4556933/rs77886248)as esophageal squamous cell carcinoma risk modifiers in Chinese Han populations through a case-control study(1264 patients/1361 controls),revealing transforming growth factor-beta pathway-mediated susceptibility in older male smokers(P<0.001).Concurrently,Luo et al established imaging-based differentiation of pancreatic cancer subtypes(pancreatic ductal adenocarcinoma vs neuroendocrine tumors)via retrospective analysis of 500 cases(area under the curve=0.89),enabling earlier intervention.These findings underscore the transformative potential of combining genetic risk stratification with advanced imaging to guide precision screening and therapeutic strategies,addressing critical gaps in esophageal and pancreatic cancer outcomes.
基金financially supported by the National Natural Science Foundation of China(NSFC,Nos.22075168,21701105,21871167&91961201)Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-FR003)。
文摘In our work,polymorphism strategy has been successfully applied to tune up chromism and luminescence properties of viologen-based materials.Two polymorphs of viologen-based complexes ofα-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2)(1)andβ-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2)(2)(PHSQ=N-(4-sulfophenyl)-4,4-bipyridinium)were synthesized by changing the solvent.They can both respond to UV light and electricity in the manner of chromism visible to the naked eye and the coloration states have good reversibility,through which an inkless erasable printing model has been established.But the coloration contrast of 1 is higher compared to 2.Meanwhile,they both exhibit photoluminescence properties and the intensity of 1 is twice that of 2,which is accompanied by photoquenching upon continuous UV light irradiation.The only divergence of disordered/ordered O atoms in the two crystalline compounds leads to significantly different chromic and luminescent properties.Further explorations simultaneously demonstrate that the different chromic performance between 1 and 2 should attribute to the alteration of stimulus-induced(light/electricity)electron transfer channels caused by the ordered/disordered O atoms in the complexes,which is achieved through C-H···O and O-H···O interactions to change crystal arrangement and structural rigidity,thus affect luminescent properties.
基金supported by grants from the National Natural Science Foundation of China(No.82173593,32300473)Guangzhou Science and Technology Project(No.2025A04J4537,2025A04J4696)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2023A1515220053)Postdoctoral Science Foundation of Jiangsu Province(No.2021K524C).
文摘Objective:Neuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings.Previous genome-wide association studies(GWASs)have identified many loci associated with neuroblastoma susceptibility;however,their application in risk prediction for Chinese children has not been systematically explored.This study seeks to enhance neuroblastoma risk prediction by validating these loci and evaluating their performance in polygenic risk models.Methods:We validated 35 GWAS-identified neuroblastoma susceptibility loci in a cohort of Chinese children,consisting of 402 neuroblastoma patients and 473 healthy controls.Genotyping these polymorphisms was conducted via the TaqMan method.Univariable and multivariable logistic regression analyses revealed the genetic loci significantly associated with neuroblastoma risk.We constructed polygenic risk models by combining these loci and assessed their predictive performance via area under the curve(AUC)analysis.We also established a polygenic risk scoring(PRS)model for risk prediction by adopting the PLINK method.Results:Fourteen loci,including ten protective polymorphisms from CASC15,BARD1,LMO1,HSD17B12,and HACE1,and four risk variants from BARD1,RSRC1,CPZ and MMP20 were significantly associated with neuroblastoma risk.Compared with single-gene model,the 8-gene model(AUC=0.72)and 13-gene model(AUC=0.73)demonstrated superior predictive performance.Additionally,a PRS incorporating six significant loci achieved an AUC of 0.66,effectively stratifying individuals into distinct risk categories regarding neuroblastoma susceptibility.A higher PRS was significantly associated with advanced International Neuroblastoma Staging System(INSS)stages,suggesting its potential for clinical risk stratification.Conclusions:Our findings validate multiple loci as neuroblastoma risk factors in Chinese children and demonstrate the utility of polygenic risk models,particularly the PRS,in improving risk prediction.These results suggest that integrating multiple genetic variants into a PRS can enhance neuroblastoma risk stratification and potentially improve early diagnosis by guiding targeted screening programs for high-risk children.
文摘Objective:This review examined the co-morbidity of malaria and hypertension in Nigerian adults,with a focus on epidemiological trends,genetic and environmental risk factors,pathophysiological mechanisms,and systemic healthcare barriers.Methods:A qualitative synthesis of peer-reviewed literature,national health surveys,and institutional reports published between 2000 and 2025 was conducted using thematic analysis.While centered on Nigeria,the review incorporated comparative insights from global studies on renin angiotensin aldosterone system polymorphisms,co-infection dynamics,and health service inequalities.Results:The findings indicate overlapping risk factors including renin angiotensin aldosterone system gene polymorphisms,urbanization,and poverty.Angiotensin Ⅱ demonstrates dual functions,contributing both to malaria suppression and to hypertension pathogenesis.Clinical challenges include diagnostic overlap,adverse drug interactions,and disparities in service delivery between rural and urban populations.These challenges particularly affect older adults and highlight systemic gaps in access,workforce distribution,and policy alignment.Conclusion:The dual burden of malaria and hypertension in Nigeria requires integrated disease management strategies that address both communicable and non-communicable disease risks.Urgent priorities include multisectoral policy reforms,expanded rural health investments,and the adoption of precision medicine approaches guided by genetic profiling.The implications extend to clinical practice through co-screening and tailored treatment protocols and to public health policy,where integrated frameworks are essential to reducing inequities and improving long-term outcomes.
文摘The amalgamation of herbal medicine and nanoformulation technology presents a compelling avenue for the advancement of pharmaceutical and health food products.This synergy capitalizes on the inherent therapeutic properties of herbal extracts while harnessing the innovative capabilities of nano-scale formulation.Nano-technology has revolutionized drug delivery systems,offering enhanced bioavailability and targeted delivery of active compounds.The global research landscape reflects a burgeoning interest in nano-based pharmaceuticals,driven by their potential to overcome traditional limitations and optimize therapeutic outcomes.Vietnam,with its rich biodiversity and burgeoning nano-industry,stands at the forefront of this convergence.Vietlife,a prominent player in health product research and manufacturing,is poised to capitalize on this convergence.By leveraging indigenous herbal knowledge and cutting-edge nanoformulation techniques,Vietlife can pioneer the development of novel pharmaceutical and health food solutions.In conclusion,the integration of herbal medicine and nanoformulation technology opens up promising opportunities for the development of pharmaceuticals and healthcare products.Vietnam and Vietlife can capitalize on this trend to drive sustainable development and establish their presence in the international market.
文摘Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism.Its genetic polymorphisms affect the metabolism of methyl donors,including folate and betaine,and are consequently associated with the development of various chronic diseases such as stroke and neoplasms.Methods This umbrella review,covering the period from 2006 to 2025,searched PubMed,Embase,Web of Science,Medline,CNKI,WanFang,and Cochrane Library databases for published systematic reviews and meta-analyses of polymorphisms relating to the MTHFR C677T and A1298C gene polymorphisms and various chronic diseases.Subsequently,this study assessed methodological quality with AMSTAR-2,while the strength of evidence for each outcome was graded according to the GRADE and the credibility evaluation.This umbrella review included 39 studies related to 8 diseases classified according to the ICD-10 classification.Results Overall,C677T exhibited a positive correlation with depression(allele:OR=1.18,95%CI:1.13-1.24;dominant:OR=1.16,95%CI:1.09-1.23;recessive:OR=1.42,95%CI:1.30-1.56;homozygote:OR=1.48,95%CI:1.34-1.63),and polycystic ovary syndrome(allele:OR=1.35,95%CI:1.24-1.46;dominant:OR=1.46,95%CI:1.30-1.64;recessive:OR=1.39,95%CI:1.19-1.62;homozygote:OR=1.63,95%CI:1.38-1.93),and exhibited a negative correlation with oral cancer(allele:OR=0.24,95%CI:0.22-0.26;dominant:OR=0.14,95%CI:0.12-0.16;recessive:OR=0.31,95%CI:0.28-0.35;homozygote:OR=0.14,95%CI:0.12-0.16).A1298C was positively associated with polycystic ovary syndrome in four models(allele:OR=1.93,95%CI:1.67-2.21;dominant:OR=1.93,95%CI:1.64-2.27;recessive:OR=3.72,95%CI:2.47-5.61;homozygote:OR=4.38,95%CI:2.90-6.62).Conclusion The MTHFR C677T and A1298C gene polymorphisms demonstrated significant associations with non-communicable diseases,thereby contributing to the advancement of precision medicine.
基金supported by the National Natural Science Foundation of China(Grant Nos.81872686 and 82173611)the National Key Research and Development Program of China(Grant No.2018YFC2000703)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine)。
文摘Hypertension(HT)is a major risk factor for cardiovascular diseases.Krüppel-like factors(KLFs)are important transcription factors in eukaryotes.Studies have reported that KLF4 and KLF5 are correlated with several cardiovascular diseases,but population-based studies on associations between HT and KLF4 or KLF5 have rarely been reported.Therefore,the current study investigated the associations of genetic variants and m RNA expression levels of KLF4 and KLF5 with HT,as well as the effects of antihypertensive drugs on the expression levels of these genes.The associations of one single-nucleotide polymorphism(SNP)in KLF4 and three SNPs in KLF5with HT were analyzed using a combination of case-control and cohort studies.The study populations were selected from a community-based cohort in four regions of Jiangsu province.The risks of HT were estimated through logistic and Cox regression analyses.In addition,m RNA expression levels of KLF4 and KLF5 were detected in 246 controls and 385 HT cases selected from the aforementioned cohort.Among the HT cases,263were not taking antihypertensive drugs[AHD(-)]and 122 were taking antihypertensive drugs[AHD(+)].In the case-control study,SNP rs9573096(C>T)in KLF5 was significantly associated with an increased risk of HT in the additive model(adjusted odds ratio[OR],1.106;95%confidence interval[CI],1.009 to 1.212).In the cohort study of the normotensive population,rs9573096 in KLF5 was also significantly associated with an increased risk of HT in the additive model(adjusted hazards ratio[HR],1.199;95%CI,1.070 to 1.344).KLF4 and KLF5m RNA expression levels were significantly higher in the AHD(-)group than in the control group(P<0.05),but lower in the AHD(+)group than in the AHD(-)group(P<0.05).The current study demonstrated the associations of KLF4 and KLF5 genetic variants with hypertension,as well as the association of the indicative variations in m RNA expression levels of KLF4 and KLF5 with the risk of hypertension and antihypertensive treatment.
文摘BACKGROUND The NaV1.1 sodium channel alpha subunit,encoded by SCN1A,is crucial for initiating and propagating action potentials in neurons.SCN1A gene has long been an established target in the etiology and therapy of epilepsy.However,very few studies have investigated the relevance of genetic variations in epilepsy and anti-epileptic drug resistance.AIM To investigate associations between polymorphisms,rs121917953 T/A and rs121918623 C/T,and drug resistance in epilepsy patients in the north Indian population.METHODS A total of 100 age-and sex-matched epilepsy patients(50 drug responsive and 50 drug resistant subjects)were recruited and SCN1A rs121918623 C/T*and rs121917953 T/A*polymorphisms were analyzed by the allele specific-PCR technique.χ^(2)and Fisher’s exact test were used to estimate differences between the distribution of SCN1A rs121918623 and rs121917953 gene polymorphisms among various groups.The association between distinct rs121917953 genotypes and drug resistance was analyzed using logistic regression analysis.RESULTS For the SCN1A rs121917953 T/A*(D188V)polymorphism,a significantly higher proportion of individuals with AT genotype were observed in the drug-resistant group as compared to the drug-responsive group.Additionally,a higher risk association was exhibited by AT genotype for drug resistance with an odds ratio of 3.51 and P value=0.017.For the SCN1A rs121918623 C/T*(T875M)polymorphism,no significant difference in genotype distribution was observed between the drug-resistant and drug-sensitive groups.CONCLUSION Our findings indicate that the SCN1A polymorphism D188V is associated with a higher risk of drug resistance for the AT variant as compared to the homozygous TT wild-type.Further research is needed at the functional level and in larger cohorts to determine the potential of these genes as a therapeutic target in epilepsy subjects.
基金Supported by the National Key Research and Development Program of China,No.2021YFC2700700 and No.2021YFC2700704Capital’s Funds for Health Improvement and Research(CFH)in People’s Republic of China,No.2020-1-5112.
文摘BACKGROUND There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus(GDM),and the correlation between genetic factors related to folic acid metabolism pathways and GDM remains to be revealed.AIM To examine the association between single-nucleotide polymorphisms(SNPs)of enzyme genes in the folate metabolite pathway as well as that between GDM-related genes and risk for GDM.METHODS A nested case-control study was conducted with GDM cases(n=412)and healthy controls(n=412).DNA was extracted blood samples and SNPs were genotyped using Agena Bioscience’s MassARRAY gene mass spectrometry system.The associations between different SNPs of genes and the risk for GDM were estimated using logistic regression models.The generalized multi-factor dimensionality reduction(GMDR)method was used to analyze gene-gene and gene-environment interactions using the GMDR 0.9 software.RESULTS The variation allele frequency of melatonin receptor 1B(MTNR1B)rs10830963 was higher in the GDM group than in controls(P<0.05).MTNR1B rs10830963 mutant G was associated with risk for GDM[adjusted odds ratio(aOR):1.43;95%confidence interval(95%CI):1.13-1.80]in the additive model.MTNR1B rs10830963 GG+GC was significantly associated with the risk for GDM(aOR:1.65;95%CI:1.23-2.22)in the dominant model.The two-locus model of MTNR1B rs10830963 and CHEMERIN rs4721 was the best model(P<0.05)for gene-gene interactions in the GMDR results.The high-risk rs10830963×rs4721 type of interaction was a risk factor for GDM(aOR:2.09;95%CI:1.49-2.93).CONCLUSION This study does not find an association between SNPs of folate metabolic enzymes and risk for GDM.The G mutant allele of MTNR1B rs10830963 is identified as a risk factor for GDM in the additive model,and there may be gene-gene interactions between MTNR1B rs10830963 and CHEMERIN rs4721.It is conducive to studying the causes of GDM and provides a new perspective for the precise prevention of this disease.
