Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidat...Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene expression.Methods:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with Af.Liver tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was performed.The GENE-E analysis platform was used to generate a clustered heat map matrix.Results:Significant variation in body weight changes between CC lines was ob-served.Hepatic gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight changes.Interestingly,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome 8.Conclusions:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af.As a next step,eQTL analysis will be performed for our RNA-Seq data.Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis.展开更多
Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinester...Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.展开更多
Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of dig...Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk.Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis.Results After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population.Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.展开更多
To identify the cause of mass mortality of adult Macrobrachium rosenbergii in a farm in Gaoyou City,Jiangsu Province,China,a dominant strain named DKQ-1 was isolated from the hepatopancreas of dying M.rosenbergii and ...To identify the cause of mass mortality of adult Macrobrachium rosenbergii in a farm in Gaoyou City,Jiangsu Province,China,a dominant strain named DKQ-1 was isolated from the hepatopancreas of dying M.rosenbergii and identified as Aeromonas dhakensis by purification culture,biochemical characterization,and 16S rRNA and gyrB gene sequence analysis.The results of the challenge test revealed that the strain was highly pathogenic and the 50%lethal dose(LD_(50))in 72 h to M.rosenbergii was 1.54×10^(5)CFU/mL.The amplification results of virulence genes show that strain DKQ-1 carried 9 virulence genes,including ascV,aexT,aer,act,lip,ompAI,gcaT,acg,and exu,supporting the strong virulence of strain DKQ-1 to M.rosenbergii.Histopathological observation of the hepatopancreas,gills,and intestines indicated that DKQ-1 injection into M.rosenbergii could cause serious tissue damage,which further supported the strong virulence of this strain.In addition,a drug susceptibility test revealed that strain DKQ-1 was sensitive to 16 kinds of antibiotics,resistant to 9 kinds of antibiotics,and had intermediate resistance to spectinomycin and kanamycin.This study is the first report of A.dhakensis isolated from M.rosenbergii and provided a reference for the pathogen identification of bacterial diseases in M.rosenbergii,and for the prevention and treatment caused by A.dhakensis.展开更多
Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular...Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.展开更多
Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the...Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided quick identification with the help of SGTF phenomenon within 5 hours of duration. This strategy helps scientists and health policymakers for the quick isolation and identification of clusters. That ultimately results in a decreased transmission of pathogen among the community.展开更多
Inflammatory bowel disease(IBD)is a disorder of the immune system and intestinal microecosystem caused by environmental factors in genetically susceptible people.Paneth cells(PCs)play a central role in IBD pathogenesi...Inflammatory bowel disease(IBD)is a disorder of the immune system and intestinal microecosystem caused by environmental factors in genetically susceptible people.Paneth cells(PCs)play a central role in IBD pathogenesis,especially in Crohn's disease development,and their morphology,number and function are regulated by susceptibility genes.In the intestine,PCs participate in the formation of the stem cell microenvironment by secreting antibacterial particles and play a role in helping maintain the intestinal microecology and intestinal mucosal homeostasis.Moreover,PC proliferation and maturation depend on symbiotic flora in the intestine.This paper describes the interactions among susceptibility genes,PCs and intestinal microecology and their effects on IBD occurrence and development.展开更多
Objective To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis.Methods A total of 1,490 cancer patients(lung/gast...Objective To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis.Methods A total of 1,490 cancer patients(lung/gastric/liver/:550/460/480)and 800 controls were recruited in this case-control study.The meta-analysis was performed by pooling the data from previous related studies and the present study.Results The results of this study showed that in the Hubei Han Chinese population,the rs10754339gene was significantly associated with the risk of lung and gastric cancer but not liver cancer,and the rs12976445 gene was significantly associated with the risk of lung cancer but not liver or gastric cancer.The meta-analysis results indicated that rs10754339 and rs12976445 contributed to cancer susceptibility in the Chinese population and also revealed a significant association between rs10754339and breast cancer risk,as well as between rs12976445 and lung cancer risk.Conclusion The B7-H4 gene rs10754339 and miR-125a gene rs12976445 may be the potential genetic markers for cancer susceptibility in the Chinese population,which should be validated in future studies with larger sample sizes in other ethnic populations.展开更多
Triggering receptor expressed on myeloid cells-like 2(TREML2)is a newly identified susceptibility gene for Alzheimer's disease(AD).It encodes a microglial inflammation-associated receptor.To date,the potential rol...Triggering receptor expressed on myeloid cells-like 2(TREML2)is a newly identified susceptibility gene for Alzheimer's disease(AD).It encodes a microglial inflammation-associated receptor.To date,the potential role of mic roglial TREML2 in neuroinflammation in the context of AD remains unclear.In this study,APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression.In addition,lipopolysaccharide(LPS)stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD.Our res ults show that TREML2 levels gradually increased in the brains of AP P/PS1 mice during disease progression.LPS stimulation of primary microglia led to the release of inflammato ry cytokines including interleukin-1β,inte rleukin-6,and tumor necrosis factor-a in the culture medium.The LPS-induced mic roglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knoc kdown.LPS increased the levels of mic roglial M1-type polarization marker inducible nitric oxide synthase.This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown.Furthermore,the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown.LPS stimulation increased the levels of NLRP3 in primary microglia.The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown.In summary,this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation.These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.展开更多
Toxic aggregated amyloid-βaccumulation is a key pathogenic event in Alzheimer’s disease.Treatment approaches have focused on the suppression,deferral,or dispersion of amyloid-βfibers and plaques.Gene therapy has ev...Toxic aggregated amyloid-βaccumulation is a key pathogenic event in Alzheimer’s disease.Treatment approaches have focused on the suppression,deferral,or dispersion of amyloid-βfibers and plaques.Gene therapy has evolved as a potential therapeutic option for treating Alzheimer’s disease,owing to its rapid advancement over the recent decade.Small interfering ribonucleic acid has recently garnered considerable attention in gene therapy owing to its ability to down-regulate genes with high sequence specificity and an almost limitless number of therapeutic targets,including those that were once considered undruggable.However,lackluster cellular uptake and the destabilization of small interfering ribonucleic acid in its biological environment restrict its therapeutic application,necessitating the development of a vector that can safeguard the genetic material from early destruction within the bloodstream while effectively delivering therapeutic genes across the bloodbrain barrier.Nanotechnology has emerged as a possible solution,and several delivery systems utilizing nanoparticles have been shown to bypass key challenges regarding small interfering ribonucleic acid delivery.By reducing the enzymatic breakdown of genetic components,nanomaterials as gene carriers have considerably enhanced the efficiency of gene therapy.Liposomes,polymeric nanoparticles,magnetic nanoparticles,dendrimers,and micelles are examples of nanocarriers that have been designed,and each has its own set of features.Furthermore,recent advances in the specific delivery of neurotrophic compounds via gene therapy have provided promising results in relation to augmenting cognitive abilities.In this paper,we highlight the use of different nanocarriers in targeted gene delivery and small interfering ribonucleic acid-mediated gene silencing as a potential platform for treating Alzheimer’s disease.展开更多
Sea cucumber Holothuria leucospilota is one of the most widespread tropical holothurian species.In this study,eukaryotic organism composition in foregut and hindgut contents of H.leucospilota and surrounding sediments...Sea cucumber Holothuria leucospilota is one of the most widespread tropical holothurian species.In this study,eukaryotic organism composition in foregut and hindgut contents of H.leucospilota and surrounding sediments was assessed by 18S rRNA gene high-throughput sequencing.Eukaryon richness and diversity in the habitat sediments were significantly higher than those in foregut and hindgut contents of the sea cucumbers(P<0.05).The foregut content group,hindgut content group,and marine sediment group sequences were respectively assigned to 18.20±1.32,19.40±1.03,and 21.80±0.37 phyla.In the foregut contents,Nematoda(20.18%±9.59%),Mollusca(16.12%±10.49%),Chlorophyta(10.04%±4.85%),Annelida(8.72%±10.93%),Streptophyta(8.46%±4.65%),and Diatomea(5.99%±2.01%)were the predominant phyla,which showed the eukaryotic food sources of H.leucospilota were primarily belong to the above phyla.The predominant phyla in the hindgut contents were Streptophyta(45.55%±17.32%),Mollusca(4.93%±4.82%),Arthropoda(5.37%±3.08%),Diatomea(3.88%±2.34%),and Chlorophyta(3.79%±1.59%);and Annelida(37.80%±17.00%),Arthropoda(24.49%±12.53%),Platyhelminthes(7.14%±3.02%),Nematoda(4.14%±0.91%),and Diatomea(5.11%±1.35%)had large contents in the sediments.The comparatively high content of Paris genus in phylum Streptophyta in foregut contents indicated that land plants were one of the primary food sources of H.leucospilota,however the significantly higher contents of Streptophyta in hindgut contents than that in foregut contents might suggest a large part of the terrigenous detritus ingested might not be digested by H.leucospilota.UPGMA and PCoA analysis revealed that eukaryotic organism composition differed significantly between foregut contents of H.leucospilota and ambient sediments,indicating selective feeding feature of H.leucospilota.This study provided useful references for artificial feed of tropical sea cucumbers and enhanced understanding of the ecological roles of detritus-feeding macrobenthos.展开更多
AIM To study the genetic susceptibility of HLA-DQA1 alleles to duodenal ulcer in Wuhan Hans.METHODS Seventy patients with duodenalulcer and fifty healthy controls were examinedfor HLA-DQA1 genotypes.HLA-DQA1 typing wa...AIM To study the genetic susceptibility of HLA-DQA1 alleles to duodenal ulcer in Wuhan Hans.METHODS Seventy patients with duodenalulcer and fifty healthy controls were examinedfor HLA-DQA1 genotypes.HLA-DQA1 typing wascarried out by digesting the locus specificpolymerase chain reaction amplified productswith alleles specific restriction enzymes(PCR-RFLP),i.e.,Apal Ⅰ,Bsaj Ⅰ,Hph Ⅰ,Fok Ⅰ,Mbo Ⅱ and Mnl Ⅰ.RESULTS The allele frequencies of DQA1 * 0301and DQA1 * 0102 in patients with duodenal ulcerwere significantly higher and lower respectivelythan those in healthy controls(0.40 vs 0.20,P = 0.003,mcorret = 0.024)and(0.05 vs 0.14,P = 0.012,but Pcorret】0.05),respectively.CONCLUSION DQA1 * 0301 is a susceptiblegene for duodenal ulcer in Wuhan Hans,andthere are immunogenetic differences in HLA-DQA1 locus between duodenal ulcer patients andhealthy controls.展开更多
AIN To study the relationship of Imp2 and DR3genes with type Ⅰ diabetes mellitus.NETHODS Imp2 genotypes and DR3 wereidentified in 68 patients with type Ⅰ diabetesmellitus(Ⅰ-DM)and 71 healthy controls.Then,Ⅰ-DM pat...AIN To study the relationship of Imp2 and DR3genes with type Ⅰ diabetes mellitus.NETHODS Imp2 genotypes and DR3 wereidentified in 68 patients with type Ⅰ diabetesmellitus(Ⅰ-DM)and 71 healthy controls.Then,Ⅰ-DM patients and controls were respectivelyallocated into DR3-positive and DR3-negativegroups.The frequencies of Imp2 and DR3 genein random subjects,and Imp2 genotypes in DR3-matched subjects were compared between Ⅰ-DMpatients and controls.At the same time,Ⅰ-DMpatients were divided into 3 groups based on theonset age of diabetics:group A≤14 years,group B 15-30 years and group C≥31 years.RESULTS The frequency of DR3 in Ⅰ-DMpatients was significantly higher than that incontrols(47% vs 21%,P【0.005),and it wassignificantly higher in group A than that in groupB+C(70% vs 36%,x^2=7.07,P【0.01).Therewas a significant difference among groups withdifferent onset age of diabetics(x^2=8.19,rp=0.33,P【0.05).In random subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(43% vs 61%,P【0.05)and Imp2.R/Hhigher(53% vs 28%,P【0.05)than that incontrols,and there was no significant differenceamong groups with different onset age ofdiabetics.In DR3-positive subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(47% vs 87%,P【0.05)and Imp2-R/H higher(47% vs 13%,P【0.05)than that incontrols.In DR3-negative subjects,thefrequency of Imp2.R/H in Ⅰ-DM patients washigher than that in controls(58% vs 32%,P【0.01),but the frequency of Imp2-R/R and Imp2H/H was not significantly different betweenthese two groups.CONCLUSION DR3 gene may be one of thesusceptible genes of Ⅰ-DM,and significantlyrelated to the onset age of diabetics,and thepersons with DR3 may have an younger onsetage of diabeteS.The Imp2-R/R may be theprotective genotype of Ⅰ-DM,and Imp2-R/H thesusceptible genotype.These were not affectedby DR3 gene.Imp-2 genotypes were not relatedwith the onset age of diabetics.展开更多
Objective:To discuss the association between single nucleotide polymorphism(SNP) of rs3811047 in IL-1 F7 gene and rheumatoid arthritis(RA) susceptibility among the Han population in central plains of China.Methods:A t...Objective:To discuss the association between single nucleotide polymorphism(SNP) of rs3811047 in IL-1 F7 gene and rheumatoid arthritis(RA) susceptibility among the Han population in central plains of China.Methods:A total of 276 RA patients admitted to our hospital from December 2009 to December 2011 together with 276 healthy physical examinees in the same period were chosen as the subjects.The typing for rs3811047 SNP in IL-1 F7 gene was carried out by using ligase detection reaction and polymerase chain reaction technique.And the frequency of each allele and genotypes distribution was calculated so as to evaluate the association between genotype distribution and RA susceptibility.Results:The frequency of A allele of rs3811047 in IL-1 F7 gene in RA group and control group was 16.27%and 17.68%,respectively,and that of G allele in two groups was 83.73%and 82.32%,respectively.The difference between two groups wasn’t statistical significant(P 】0.05).The frequency of genotype AA,AG and GG in RA group was 2.19%,27.84%and 69.97%,respectively,while that in control group was 2.94%,29.78%and 67.28%, respectively.The difference of distribution of three genotypes was not statistically significant (P 】0.05).RA patients with A allele were better than those without A allele in joint swelling index, rest pain,HAQ scoring and blood sedimentation.There was significant difference between two groups in above indexes(P【0.05/P【0.01).Conclusions:No significant correlation between RA susceptibility among the Han population in central plains of China and rs3811047 SNP inIL-1 F7 gene is observed.However,A allele of rs3811047 has certain influence on the condition of RA patients.展开更多
Objective:There are many hereditary breast cancer patients in China,and multigene panel testing has been a new paradigm of genetic testing for these patients and their relatives.However,the magnitude of breast cancer ...Objective:There are many hereditary breast cancer patients in China,and multigene panel testing has been a new paradigm of genetic testing for these patients and their relatives.However,the magnitude of breast cancer risks related to multiple breast cancer susceptibility genes are largely unknown in Chinese women.Methods:We screened pathogenic variants in 15 established or potential breast cancer susceptibility genes from 8,067 consecutive Chinese female breast cancer patients and 13,129 Chinese cancer-free female controls.These breast cancer patients were unselected for age at diagnosis or family history.Results:We found that pathogenic variants in TP53[odds ratio(OR):16.9,95%confidence interval(CI):5.2–55.2];BRCA2(OR:10.4,95%CI:7.6–14.2);BRCA1(OR:9.7,95%CI:6.3–14.8);and PALB2(OR:5.2,95%CI:3.0–8.8)were associated with a high risk of breast cancer.ATM,BARD1,CHEK2,and RAD51D were associated with a moderate risk of breast cancer with ORs ranging from 2-fold to 4-fold.In contrast,pathogenic variants of NBN,RAD50,BRIP1,and RAD51C were not associated with increased risk of breast cancer in Chinese women.The pathogenic variants of PTEN,CDH1,and STK11 were very rare,so they had a limited contribution to Chinese breast cancer.Patients with pathogenic variants of TP53,BRCA1,BRCA2,and PALB2 more often had earlyonset breast cancer,bilateral breast cancer,and a family history of breast cancer and/or any cancer.Conclusions:This study provided breast cancer risk assessment data for multiple genes in Chinese women,which is useful for genetic testing and clinical management of Chinese hereditary breast cancer.展开更多
Gene expression(GE)classification is a research trend as it has been used to diagnose and prognosis many diseases.Employing machine learning(ML)in the prediction of many diseases based on GE data has been a flourishin...Gene expression(GE)classification is a research trend as it has been used to diagnose and prognosis many diseases.Employing machine learning(ML)in the prediction of many diseases based on GE data has been a flourishing research area.However,some diseases,like Alzheimer’s disease(AD),have not received considerable attention,probably owing to data scarcity obstacles.In this work,we shed light on the prediction of AD from GE data accurately using ML.Our approach consists of four phases:preprocessing,gene selection(GS),classification,and performance validation.In the preprocessing phase,gene columns are preprocessed identically.In the GS phase,a hybrid filtering method and embedded method are used.In the classification phase,three ML models are implemented using the bare minimum of the chosen genes obtained from the previous phase.The final phase is to validate the performance of these classifiers using different metrics.The crux of this article is to select the most informative genes from the hybrid method,and the best ML technique to predict AD using this minimal set of genes.Five different datasets are used to achieve our goal.We predict AD with impressive values forMultiLayer Perceptron(MLP)classifier which has the best performance metrics in four datasets,and the Support Vector Machine(SVM)achieves the highest performance values in only one dataset.We assessed the classifiers using sevenmetrics;and received impressive results,allowing for a credible performance rating.The metrics values we obtain in our study lie in the range[.97,.99]for the accuracy(Acc),[.97,.99]for F1-score,[.94,.98]for kappa index,[.97,.99]for area under curve(AUC),[.95,1]for precision,[.98,.99]for sensitivity(recall),and[.98,1]for specificity.With these results,the proposed approach outperforms recent interesting results.With these results,the proposed approach outperforms recent interesting results.展开更多
Objective:To explore the correlation between coronary heart disease related genes and coronary heart disease in hospitalized patients in Hainan,and to provide theoretical basis for enriching the screening methods of h...Objective:To explore the correlation between coronary heart disease related genes and coronary heart disease in hospitalized patients in Hainan,and to provide theoretical basis for enriching the screening methods of high-risk groups of coronary heart disease in Hainan,and optimizing the prevention and treatment strategies.Methods:We select hospitalized patients born in Hainan and aged>30 years old from the Second Affiliated Hospital of Hainan Medical Unversity between January 1,2020 and June 30,2022,and divided the patients into the coronary heart disease group and the non-coronary heart disease group.PCR real-time fluorescence was used to measure gene expression,and Spearman correlation analysis was used to explore the correlation between gene expression and coronary heart disease.Results:A total of 55 whole blood samples were collected from non-coronary heart disease patients(including 26 women and 29 men),with a median age of 57 years,and 170 whole blood samples from coronary heart disease patients(including 44 women and 126 men),with a median age of 63.17.Apolipoprotein B gene(ApoB)was highly expressed in patients with coronary heart disease(P<0.001);AGT gene(P=0.0158),ApoE gene(P=0.0126),FGB gene(P=0.005),GNB gene(P=0.0151),MTFHR gene(P=0.0119),SEL gene(P=0.005),TNF gene(P=0.0298)were significantly overexpressed in the non-coronary heart disease group.The expression of NOS3 gene(P=0.3047),IL6 gene(P=0.7239),ACE gene(P=0.7852)was not different between the two groups.Coronary heart disease was negatively correlated with AGT gene(r=-0.163,P=0.011,P<0.05),positively correlated with APOB gene(r=0.75,P=0,P<0.01),negatively correlated with FGB gene(r=-0.163,P=0.011,P<0.05),negatively correlated with GNB gene(r=-0.165,P=0.011,P<0.05),negatively correlated withSEL gene(r=-0.171,P=0.007,P<0.01),negatively correlated with MHTHR gene(r=-0.210,P=0.001,P<0.01)and negatively correlated with TNF gene(r=-0.131,P=0.04,P<0.05),but coronary heart disease was not correlated with APOE,NOS3,ACE,IL6 and other genes(P>0.05).The ApoB gene of coronary heart disease was negatively correlated with triglyceride(r=-0.461,P=0),positively correlated with age(r=0.173,P=0.009),positively correlated with total cholesterol(r=0.499,P=0),negatively correlated with high-density lipoprotein(r=-0.181,P=0.007),and negatively correlated with low-density lipoprotein(r=-0.143,P=0.031).Conclusion:(1)The detection of apolipoprotein B gene expression may be used as an indicator for screening coronary heart disease in the coronary population in Hainan.It may increase the risk of coronary heart disease by affecting the level of total cholesterol.A larger sample of research is still needed.(2)AGT,ApoE,FGB,GNB,MTFHR,SELE,TNF and other genes may be the protective genes of non-coronary heart disease population in Hainan,and the high expression of these genes may reduce the occurrence of coronary heart disease,which still needs further study.展开更多
基金European Sequencing and Genotyping Institutes(ESGI),Grant/Award Number:075491/Z/04,085906/Z/08/Z and 090532/Z/09/ZTel-Aviv University(TAU)。
文摘Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene expression.Methods:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with Af.Liver tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was performed.The GENE-E analysis platform was used to generate a clustered heat map matrix.Results:Significant variation in body weight changes between CC lines was ob-served.Hepatic gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight changes.Interestingly,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome 8.Conclusions:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af.As a next step,eQTL analysis will be performed for our RNA-Seq data.Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis.
文摘Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.
基金supported by the Fundamental Research Funds for the Central Universities(WUT:2020IB029)。
文摘Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk.Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis.Results After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population.Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.
基金Supported by the Earmarked Fund for the China Agriculture Research System(No.CARS-48)the Key Scientific and Technological Grant of Zhejiang for Breeding New Agricultural Varieties(No.2021 C 02069-4-3)the Major Research&Development Program(modern agriculture)of Jiangsu Province(No.BE 2019352)。
文摘To identify the cause of mass mortality of adult Macrobrachium rosenbergii in a farm in Gaoyou City,Jiangsu Province,China,a dominant strain named DKQ-1 was isolated from the hepatopancreas of dying M.rosenbergii and identified as Aeromonas dhakensis by purification culture,biochemical characterization,and 16S rRNA and gyrB gene sequence analysis.The results of the challenge test revealed that the strain was highly pathogenic and the 50%lethal dose(LD_(50))in 72 h to M.rosenbergii was 1.54×10^(5)CFU/mL.The amplification results of virulence genes show that strain DKQ-1 carried 9 virulence genes,including ascV,aexT,aer,act,lip,ompAI,gcaT,acg,and exu,supporting the strong virulence of strain DKQ-1 to M.rosenbergii.Histopathological observation of the hepatopancreas,gills,and intestines indicated that DKQ-1 injection into M.rosenbergii could cause serious tissue damage,which further supported the strong virulence of this strain.In addition,a drug susceptibility test revealed that strain DKQ-1 was sensitive to 16 kinds of antibiotics,resistant to 9 kinds of antibiotics,and had intermediate resistance to spectinomycin and kanamycin.This study is the first report of A.dhakensis isolated from M.rosenbergii and provided a reference for the pathogen identification of bacterial diseases in M.rosenbergii,and for the prevention and treatment caused by A.dhakensis.
基金supported by the National Natural Science Foundation of China,No.82101340(to FJ).
文摘Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.
文摘Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided quick identification with the help of SGTF phenomenon within 5 hours of duration. This strategy helps scientists and health policymakers for the quick isolation and identification of clusters. That ultimately results in a decreased transmission of pathogen among the community.
文摘Inflammatory bowel disease(IBD)is a disorder of the immune system and intestinal microecosystem caused by environmental factors in genetically susceptible people.Paneth cells(PCs)play a central role in IBD pathogenesis,especially in Crohn's disease development,and their morphology,number and function are regulated by susceptibility genes.In the intestine,PCs participate in the formation of the stem cell microenvironment by secreting antibacterial particles and play a role in helping maintain the intestinal microecology and intestinal mucosal homeostasis.Moreover,PC proliferation and maturation depend on symbiotic flora in the intestine.This paper describes the interactions among susceptibility genes,PCs and intestinal microecology and their effects on IBD occurrence and development.
基金supported by the Fundamental Research Funds for the Central Universities (WUT:2020IB029)。
文摘Objective To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis.Methods A total of 1,490 cancer patients(lung/gastric/liver/:550/460/480)and 800 controls were recruited in this case-control study.The meta-analysis was performed by pooling the data from previous related studies and the present study.Results The results of this study showed that in the Hubei Han Chinese population,the rs10754339gene was significantly associated with the risk of lung and gastric cancer but not liver cancer,and the rs12976445 gene was significantly associated with the risk of lung cancer but not liver or gastric cancer.The meta-analysis results indicated that rs10754339 and rs12976445 contributed to cancer susceptibility in the Chinese population and also revealed a significant association between rs10754339and breast cancer risk,as well as between rs12976445 and lung cancer risk.Conclusion The B7-H4 gene rs10754339 and miR-125a gene rs12976445 may be the potential genetic markers for cancer susceptibility in the Chinese population,which should be validated in future studies with larger sample sizes in other ethnic populations.
基金supported by the National Natural Science Foundation of china,No.81974156(to TJ)the Natural Science Foundation of Jiangsu Province,No.BK20201117(to YDZ)。
文摘Triggering receptor expressed on myeloid cells-like 2(TREML2)is a newly identified susceptibility gene for Alzheimer's disease(AD).It encodes a microglial inflammation-associated receptor.To date,the potential role of mic roglial TREML2 in neuroinflammation in the context of AD remains unclear.In this study,APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression.In addition,lipopolysaccharide(LPS)stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD.Our res ults show that TREML2 levels gradually increased in the brains of AP P/PS1 mice during disease progression.LPS stimulation of primary microglia led to the release of inflammato ry cytokines including interleukin-1β,inte rleukin-6,and tumor necrosis factor-a in the culture medium.The LPS-induced mic roglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knoc kdown.LPS increased the levels of mic roglial M1-type polarization marker inducible nitric oxide synthase.This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown.Furthermore,the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown.LPS stimulation increased the levels of NLRP3 in primary microglia.The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown.In summary,this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation.These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.
基金supported by the Intramural Research Program National Institute on Aginq,NIH。
文摘Toxic aggregated amyloid-βaccumulation is a key pathogenic event in Alzheimer’s disease.Treatment approaches have focused on the suppression,deferral,or dispersion of amyloid-βfibers and plaques.Gene therapy has evolved as a potential therapeutic option for treating Alzheimer’s disease,owing to its rapid advancement over the recent decade.Small interfering ribonucleic acid has recently garnered considerable attention in gene therapy owing to its ability to down-regulate genes with high sequence specificity and an almost limitless number of therapeutic targets,including those that were once considered undruggable.However,lackluster cellular uptake and the destabilization of small interfering ribonucleic acid in its biological environment restrict its therapeutic application,necessitating the development of a vector that can safeguard the genetic material from early destruction within the bloodstream while effectively delivering therapeutic genes across the bloodbrain barrier.Nanotechnology has emerged as a possible solution,and several delivery systems utilizing nanoparticles have been shown to bypass key challenges regarding small interfering ribonucleic acid delivery.By reducing the enzymatic breakdown of genetic components,nanomaterials as gene carriers have considerably enhanced the efficiency of gene therapy.Liposomes,polymeric nanoparticles,magnetic nanoparticles,dendrimers,and micelles are examples of nanocarriers that have been designed,and each has its own set of features.Furthermore,recent advances in the specific delivery of neurotrophic compounds via gene therapy have provided promising results in relation to augmenting cognitive abilities.In this paper,we highlight the use of different nanocarriers in targeted gene delivery and small interfering ribonucleic acid-mediated gene silencing as a potential platform for treating Alzheimer’s disease.
基金Supported by the National Natural Science Foundation of China(Nos.42166005,42076097)the Hainan Provincial Key Research and Development Program(No.ZDYF2021XDNY130)+1 种基金the Natural Science Foundation of Hainan Province(No.321RC1023)the State Key Laboratory of Marine Resource Utilization in South China Sea Open Project(No.MRUKF2021008)。
文摘Sea cucumber Holothuria leucospilota is one of the most widespread tropical holothurian species.In this study,eukaryotic organism composition in foregut and hindgut contents of H.leucospilota and surrounding sediments was assessed by 18S rRNA gene high-throughput sequencing.Eukaryon richness and diversity in the habitat sediments were significantly higher than those in foregut and hindgut contents of the sea cucumbers(P<0.05).The foregut content group,hindgut content group,and marine sediment group sequences were respectively assigned to 18.20±1.32,19.40±1.03,and 21.80±0.37 phyla.In the foregut contents,Nematoda(20.18%±9.59%),Mollusca(16.12%±10.49%),Chlorophyta(10.04%±4.85%),Annelida(8.72%±10.93%),Streptophyta(8.46%±4.65%),and Diatomea(5.99%±2.01%)were the predominant phyla,which showed the eukaryotic food sources of H.leucospilota were primarily belong to the above phyla.The predominant phyla in the hindgut contents were Streptophyta(45.55%±17.32%),Mollusca(4.93%±4.82%),Arthropoda(5.37%±3.08%),Diatomea(3.88%±2.34%),and Chlorophyta(3.79%±1.59%);and Annelida(37.80%±17.00%),Arthropoda(24.49%±12.53%),Platyhelminthes(7.14%±3.02%),Nematoda(4.14%±0.91%),and Diatomea(5.11%±1.35%)had large contents in the sediments.The comparatively high content of Paris genus in phylum Streptophyta in foregut contents indicated that land plants were one of the primary food sources of H.leucospilota,however the significantly higher contents of Streptophyta in hindgut contents than that in foregut contents might suggest a large part of the terrigenous detritus ingested might not be digested by H.leucospilota.UPGMA and PCoA analysis revealed that eukaryotic organism composition differed significantly between foregut contents of H.leucospilota and ambient sediments,indicating selective feeding feature of H.leucospilota.This study provided useful references for artificial feed of tropical sea cucumbers and enhanced understanding of the ecological roles of detritus-feeding macrobenthos.
文摘AIM To study the genetic susceptibility of HLA-DQA1 alleles to duodenal ulcer in Wuhan Hans.METHODS Seventy patients with duodenalulcer and fifty healthy controls were examinedfor HLA-DQA1 genotypes.HLA-DQA1 typing wascarried out by digesting the locus specificpolymerase chain reaction amplified productswith alleles specific restriction enzymes(PCR-RFLP),i.e.,Apal Ⅰ,Bsaj Ⅰ,Hph Ⅰ,Fok Ⅰ,Mbo Ⅱ and Mnl Ⅰ.RESULTS The allele frequencies of DQA1 * 0301and DQA1 * 0102 in patients with duodenal ulcerwere significantly higher and lower respectivelythan those in healthy controls(0.40 vs 0.20,P = 0.003,mcorret = 0.024)and(0.05 vs 0.14,P = 0.012,but Pcorret】0.05),respectively.CONCLUSION DQA1 * 0301 is a susceptiblegene for duodenal ulcer in Wuhan Hans,andthere are immunogenetic differences in HLA-DQA1 locus between duodenal ulcer patients andhealthy controls.
文摘AIN To study the relationship of Imp2 and DR3genes with type Ⅰ diabetes mellitus.NETHODS Imp2 genotypes and DR3 wereidentified in 68 patients with type Ⅰ diabetesmellitus(Ⅰ-DM)and 71 healthy controls.Then,Ⅰ-DM patients and controls were respectivelyallocated into DR3-positive and DR3-negativegroups.The frequencies of Imp2 and DR3 genein random subjects,and Imp2 genotypes in DR3-matched subjects were compared between Ⅰ-DMpatients and controls.At the same time,Ⅰ-DMpatients were divided into 3 groups based on theonset age of diabetics:group A≤14 years,group B 15-30 years and group C≥31 years.RESULTS The frequency of DR3 in Ⅰ-DMpatients was significantly higher than that incontrols(47% vs 21%,P【0.005),and it wassignificantly higher in group A than that in groupB+C(70% vs 36%,x^2=7.07,P【0.01).Therewas a significant difference among groups withdifferent onset age of diabetics(x^2=8.19,rp=0.33,P【0.05).In random subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(43% vs 61%,P【0.05)and Imp2.R/Hhigher(53% vs 28%,P【0.05)than that incontrols,and there was no significant differenceamong groups with different onset age ofdiabetics.In DR3-positive subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(47% vs 87%,P【0.05)and Imp2-R/H higher(47% vs 13%,P【0.05)than that incontrols.In DR3-negative subjects,thefrequency of Imp2.R/H in Ⅰ-DM patients washigher than that in controls(58% vs 32%,P【0.01),but the frequency of Imp2-R/R and Imp2H/H was not significantly different betweenthese two groups.CONCLUSION DR3 gene may be one of thesusceptible genes of Ⅰ-DM,and significantlyrelated to the onset age of diabetics,and thepersons with DR3 may have an younger onsetage of diabeteS.The Imp2-R/R may be theprotective genotype of Ⅰ-DM,and Imp2-R/H thesusceptible genotype.These were not affectedby DR3 gene.Imp-2 genotypes were not relatedwith the onset age of diabetics.
文摘Objective:To discuss the association between single nucleotide polymorphism(SNP) of rs3811047 in IL-1 F7 gene and rheumatoid arthritis(RA) susceptibility among the Han population in central plains of China.Methods:A total of 276 RA patients admitted to our hospital from December 2009 to December 2011 together with 276 healthy physical examinees in the same period were chosen as the subjects.The typing for rs3811047 SNP in IL-1 F7 gene was carried out by using ligase detection reaction and polymerase chain reaction technique.And the frequency of each allele and genotypes distribution was calculated so as to evaluate the association between genotype distribution and RA susceptibility.Results:The frequency of A allele of rs3811047 in IL-1 F7 gene in RA group and control group was 16.27%and 17.68%,respectively,and that of G allele in two groups was 83.73%and 82.32%,respectively.The difference between two groups wasn’t statistical significant(P 】0.05).The frequency of genotype AA,AG and GG in RA group was 2.19%,27.84%and 69.97%,respectively,while that in control group was 2.94%,29.78%and 67.28%, respectively.The difference of distribution of three genotypes was not statistically significant (P 】0.05).RA patients with A allele were better than those without A allele in joint swelling index, rest pain,HAQ scoring and blood sedimentation.There was significant difference between two groups in above indexes(P【0.05/P【0.01).Conclusions:No significant correlation between RA susceptibility among the Han population in central plains of China and rs3811047 SNP inIL-1 F7 gene is observed.However,A allele of rs3811047 has certain influence on the condition of RA patients.
基金This study was supported by grants from the National Natural Science Foundation of China(Grant Nos.81772824,81372832,and 81974422).
文摘Objective:There are many hereditary breast cancer patients in China,and multigene panel testing has been a new paradigm of genetic testing for these patients and their relatives.However,the magnitude of breast cancer risks related to multiple breast cancer susceptibility genes are largely unknown in Chinese women.Methods:We screened pathogenic variants in 15 established or potential breast cancer susceptibility genes from 8,067 consecutive Chinese female breast cancer patients and 13,129 Chinese cancer-free female controls.These breast cancer patients were unselected for age at diagnosis or family history.Results:We found that pathogenic variants in TP53[odds ratio(OR):16.9,95%confidence interval(CI):5.2–55.2];BRCA2(OR:10.4,95%CI:7.6–14.2);BRCA1(OR:9.7,95%CI:6.3–14.8);and PALB2(OR:5.2,95%CI:3.0–8.8)were associated with a high risk of breast cancer.ATM,BARD1,CHEK2,and RAD51D were associated with a moderate risk of breast cancer with ORs ranging from 2-fold to 4-fold.In contrast,pathogenic variants of NBN,RAD50,BRIP1,and RAD51C were not associated with increased risk of breast cancer in Chinese women.The pathogenic variants of PTEN,CDH1,and STK11 were very rare,so they had a limited contribution to Chinese breast cancer.Patients with pathogenic variants of TP53,BRCA1,BRCA2,and PALB2 more often had earlyonset breast cancer,bilateral breast cancer,and a family history of breast cancer and/or any cancer.Conclusions:This study provided breast cancer risk assessment data for multiple genes in Chinese women,which is useful for genetic testing and clinical management of Chinese hereditary breast cancer.
文摘Gene expression(GE)classification is a research trend as it has been used to diagnose and prognosis many diseases.Employing machine learning(ML)in the prediction of many diseases based on GE data has been a flourishing research area.However,some diseases,like Alzheimer’s disease(AD),have not received considerable attention,probably owing to data scarcity obstacles.In this work,we shed light on the prediction of AD from GE data accurately using ML.Our approach consists of four phases:preprocessing,gene selection(GS),classification,and performance validation.In the preprocessing phase,gene columns are preprocessed identically.In the GS phase,a hybrid filtering method and embedded method are used.In the classification phase,three ML models are implemented using the bare minimum of the chosen genes obtained from the previous phase.The final phase is to validate the performance of these classifiers using different metrics.The crux of this article is to select the most informative genes from the hybrid method,and the best ML technique to predict AD using this minimal set of genes.Five different datasets are used to achieve our goal.We predict AD with impressive values forMultiLayer Perceptron(MLP)classifier which has the best performance metrics in four datasets,and the Support Vector Machine(SVM)achieves the highest performance values in only one dataset.We assessed the classifiers using sevenmetrics;and received impressive results,allowing for a credible performance rating.The metrics values we obtain in our study lie in the range[.97,.99]for the accuracy(Acc),[.97,.99]for F1-score,[.94,.98]for kappa index,[.97,.99]for area under curve(AUC),[.95,1]for precision,[.98,.99]for sensitivity(recall),and[.98,1]for specificity.With these results,the proposed approach outperforms recent interesting results.With these results,the proposed approach outperforms recent interesting results.
基金This study was supported by the High-level Talents Project of Hainan Basic and Applied Basic Research Program(Natural Sciences)in 2019(2019RC382)。
文摘Objective:To explore the correlation between coronary heart disease related genes and coronary heart disease in hospitalized patients in Hainan,and to provide theoretical basis for enriching the screening methods of high-risk groups of coronary heart disease in Hainan,and optimizing the prevention and treatment strategies.Methods:We select hospitalized patients born in Hainan and aged>30 years old from the Second Affiliated Hospital of Hainan Medical Unversity between January 1,2020 and June 30,2022,and divided the patients into the coronary heart disease group and the non-coronary heart disease group.PCR real-time fluorescence was used to measure gene expression,and Spearman correlation analysis was used to explore the correlation between gene expression and coronary heart disease.Results:A total of 55 whole blood samples were collected from non-coronary heart disease patients(including 26 women and 29 men),with a median age of 57 years,and 170 whole blood samples from coronary heart disease patients(including 44 women and 126 men),with a median age of 63.17.Apolipoprotein B gene(ApoB)was highly expressed in patients with coronary heart disease(P<0.001);AGT gene(P=0.0158),ApoE gene(P=0.0126),FGB gene(P=0.005),GNB gene(P=0.0151),MTFHR gene(P=0.0119),SEL gene(P=0.005),TNF gene(P=0.0298)were significantly overexpressed in the non-coronary heart disease group.The expression of NOS3 gene(P=0.3047),IL6 gene(P=0.7239),ACE gene(P=0.7852)was not different between the two groups.Coronary heart disease was negatively correlated with AGT gene(r=-0.163,P=0.011,P<0.05),positively correlated with APOB gene(r=0.75,P=0,P<0.01),negatively correlated with FGB gene(r=-0.163,P=0.011,P<0.05),negatively correlated with GNB gene(r=-0.165,P=0.011,P<0.05),negatively correlated withSEL gene(r=-0.171,P=0.007,P<0.01),negatively correlated with MHTHR gene(r=-0.210,P=0.001,P<0.01)and negatively correlated with TNF gene(r=-0.131,P=0.04,P<0.05),but coronary heart disease was not correlated with APOE,NOS3,ACE,IL6 and other genes(P>0.05).The ApoB gene of coronary heart disease was negatively correlated with triglyceride(r=-0.461,P=0),positively correlated with age(r=0.173,P=0.009),positively correlated with total cholesterol(r=0.499,P=0),negatively correlated with high-density lipoprotein(r=-0.181,P=0.007),and negatively correlated with low-density lipoprotein(r=-0.143,P=0.031).Conclusion:(1)The detection of apolipoprotein B gene expression may be used as an indicator for screening coronary heart disease in the coronary population in Hainan.It may increase the risk of coronary heart disease by affecting the level of total cholesterol.A larger sample of research is still needed.(2)AGT,ApoE,FGB,GNB,MTFHR,SELE,TNF and other genes may be the protective genes of non-coronary heart disease population in Hainan,and the high expression of these genes may reduce the occurrence of coronary heart disease,which still needs further study.