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Abstract Introduction: Anoectochilus formosanus is a highly valuable herb known for its efficacy in treating a wide range of diseases. However, the current methods used to differentiate this species from others within the same genus are not effective due to the high similarity in morphological characteristics and DNA barcode sequences among these species. Objective: To characterize the chloroplast (cp) genome to distinguish A. formosanus at species or isolation levels. Methods: The complete cp genome was sequenced using next-generation sequencing technology, annotated, and compared with published cp genomes of various species within the Anoectochilus genus. Results: The complete cp genome of A. formosanus is 152 658 bp in size, consisting of a large and small copy of 82 692 bp and 17 346 bp, respectively, separated by inverted repeats of 26 310 bp. Within the cp genome, there are a total of 141 genes, including 92 protein-coding genes, 10 rRNA genes, and 39 tRNA genes. This genome contains a total of 80 simple sequence repeats, with 50 long repeats. Through phylogenetic analysis, a close relationship was observed between A. formosanus in Vietnam and A. formosanus samples from China (NC_061756.1). However, genomic comparisons highlighted differences between the two cp genomes, specifically in their reverse repeat sequences. Conclusion: These findings reveal distinct variations in the cp genome of A. formosanus in Vietnam, offering valuable insights into the taxonomy, plant identification, breeding, and conservation programs related to this herb in Vietnam.
Resumen Introducción: Anoectochilus formosanus es una orquídea herbácea muy valiosa, conocida por su eficacia en el tratamiento de una amplia gama de enfermedades. Sin embargo, los métodos actuales utilizados para diferenciar esta especie de otras dentro del mismo género no son efectivos debido a la gran similitud en las características morfológicas y las secuencias de códigos de barras de ADN entre estas especies. Objetivo: Caracterizar el genoma del cloroplasto (cp) para distinguir A. formosanus a nivel de especie o de aislamiento. Métodos: El genoma completo del cp se secuenció utilizando tecnología de secuenciación de nueva generación, se anotó y se comparó con los genomas del cp publicados de varias especies del género Anoectochilus. Resultados: El genoma del cp completo de A. formosanus tiene un tamaño de 152 658 pb y consta de una copia grande y pequeña de 82 692 pb y 17 346 pb, respectivamente, separadas por repeticiones invertidas de 26 310 pb. Dentro del genoma del cp, hay un total de 141 genes, incluidos 92 genes codificadores de proteínas, 10 genes de ARNr y 39 genes de ARNt. Este genoma contiene un total de 80 repeticiones de secuencia simple, con 50 repeticiones largas. Mediante análisis filogenético, se observó una estrecha relación entre A. formosanus de Vietnam y muestras de A. formosanus de China (NC_061756.1). Sin embargo, las comparaciones genómicas resaltaron diferencias entre los dos genomas del cp, específicamente en sus secuencias de repetición invertida. Conclusión: Estos hallazgos revelan distintas variaciones en el genoma del cp de A. formosanus en Vietnam, lo que ofrece información valiosa sobre la taxonomía, la identificación de plantas, la reproducción y los programas de conservación relacionados con esta hierba en Vietnam.
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Resumen Durante las últimas décadas la medicina genómica ha llevado al ámbito de la consulta médica los conoci mientos de la genética molecular. Existe un número de estudios que contribuyen en el diagnóstico, la definición de pronósticos y posibilitan un asesoramiento genético basado en datos científicos certeros. En algunas enfer medades, los avances en la secuenciación genómica, ha promovido la reclasificación de entidades según un criterio etiológico, como las encefalopatías epilépticas, las ataxias, las distonías, entre muchas condiciones médicas. Su implementación requiere, por parte de los médicos, de estrategias tendientes a alcanzar el mejor rédito diagnóstico. Es necesario para ello, una mayor comprensión de las bases moleculares de estas prácti cas, así como sus alcances. Permiten reducir los tiempos hasta la concreción de un diagnóstico de certeza y la posibilidad, en algunos casos, de mejorar la calidad de vida de los afectados con la utilización de tratamientos a la medida. El objetivo de este artículo fue describir las técnicas de laboratorio actuales, sus alcances y enfatizar los algoritmos de estudio de las enfermedades genéticas, haciendo hincapié en aquellas propias de la neurope diatría, a fin de propiciar las buenas prácticas, evitando confusiones, errores, erogaciones innecesarias de dinero y acortando la llamada "odisea diagnóstica".
Abstract During the last decades, genomic medicine has made it possible to bring the knowledge of molecular genetics to the field of medical consultation. There are several studies that contribute to the diagnosis, the definition of prognoses, as well as the possibility of providing genetic counseling based on accurate scientific data. Advances in genomic sequencing have promoted the reclassifica tion of entities according to an etiological criterion. Such is the case of epileptic encephalopathies, ataxias, dystonias, among many other neurological conditions. Its implementation requires strategies aimed at achiev ing the best diagnostic yield. This requires a greater understanding of the molecular bases of each of these practices, as well as their scope. They allow reducing the time until a certain diagnosis is made and the possibility, in some cases, of improving the quality of life of those affected with the use of tailored treatments. The objective of this article was to describe current laboratory studies, their scope and emphasize the algo rithms for the study of genetic diseases in general, fo cusing the attention on those specific to neuropediatrics, in order to promote good practices, avoiding confusion, errors, and unnecessary expenditures of money and shortening the so-called "diagnostic odyssey".
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Objective In this study, a strain of colistin and tigecycline-resistant bacteria isolated in 2009 was analyzed, and the structure of drug-resistant plasmid and genetic environment were discussed, so as to provide basis for the prevention and control of multidrug-resistant bacteria. Methods A strain (GZ12244) with positive mcr and tet(M) was obtained by screening colistin and tigecycline resistance genes. Vitek-2 was used for strain identification, and the drug sensitivity test was carried out by broth dilution method. The molecular typing, drug resistance genes, insertion sequences, plasmid structure and genetic background were analyzed by genome-wide sequencing and bioinformatics. Results Strain GZ12244 is Klebsiella pneumoniae, which is resistant to colistin B, tigecycline, cefuroxime and tetracycline, and carries a variety of drug-resistant related genes such as mcr-1 and tet(M), and some of the drug-resistant genes with antibiotic efflux and antibiotic target change have amino acid substitution mutations. Mcr-1 and tet(M) coexist in a plasmid, and mcr-1 flanked by two insertion sequences ISApl1. There are insertion sequences such as IS15, IS1D and ISEc63 in the upstream and downstream of tet(M) gene. Conclusion Klebsiella pneumoniae GZ12244 is a multidrug-resistant strain. The drug-resistant gene exists in plasmid, and the mobile elements in upstream and downstream may spread the drug-resistant gene.
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Optical genome mapping (OGM) is a novel non-sequencing genetic analysis technology that enables high-precision analysis of structural variations across the entire genome. It possesses unique technical advantages, and its procedural simplicity makes it easy to implement. In recent years, the application efficacy of OGM technology in the analysis of genomic structural variations in hematologic malignancies has been widely validated and recognized. Increasing evidence indicates that the application of OGM technology can help improve the genetic diagnosis, prognostic stratification and treatment guidance of hematologic malignancies. This article draws upon pertinent reports from the 65th American Society of Hematology Annual Meeting to provide an overview of the progress in applying OGM technology for the precise diagnosis and treatment of hematologic malignancies.
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Objective To compare the categorical agreement between drug susceptibility testing(DST)and whole genome sequencing(WGS)for the detection of drug resistance in Mycobacterium tuberculosis(MTB),and to explore the characteristics of WGS for MTB drug resistance detection.Methods A total of 71 MTB clinical isolates retained in West China Hospital of Sichuan University from 2018 to 2020 were included in this study.The MTB strains were tested for resistance to 14 anti-tuberculosis drugs,including Isoniazid(INH),Rifampicin(RIF),Rifabutin(RFB),Ethambutol(EMB),Streptomycin(SM),Moxifloxacin(MFX),Ofloxacin(OFX),Levofloxacin(LFX),Amikacin(AMK),Kanamycin(KAN),Capreomycin(CPM),Para-aminosalicylic acid(PAS),Ethionamide(ETH)and Clofazimine(CLO),using both DST(colorimetric redox indicator meth-od)and WGS methods.Kappa test was performed to analyze the results of drug resistance detection for both methods.Results Based on DST and WGS methods to detect anti-tuberculosis drug resistance in seventy-one MTB clinical isolates,the results showed that the agreement rate of RIF,RFB,SM,MFX,OFX and LFX ex-ceeded 90.00％,and the kappa values were all greater than 0.80,with near perfect agreement;The agreement rates of INH and EMB were 84.51％and 81.69％,and Kappa values were 0.68 and 0.54,respectively,with fair agreement.No more than two drug resistant MTB strains of AMK and KAN were detected by both meth-ods,and the resistance rate was less than 3.00％.The agreement rates of CPM,ETH,PAS,and CLO ranged from 61.97％to 91.55％,and the Kappa values were less than 0.40,with slight or fair agreement.Conclusion There are differences in the ability of WGS to detect resistance to various anti-tuberculosis drugs,and it is more effective in detecting resistance to six anti-tuberculosis drugs,including RIF,RFB,SM,MFX,OFX and LFX,while there are still certain differences in detecting resistance to other anti-tuberculosis drugs compared with DST.It is necessary to further clarify the detailed resistance mechanisms of relevant anti-tu-berculosis drugs and to explore the standardization of WGS for drug resistance detection.
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Abstact:Objective To investigate the gene expression differences between left-sided colon cancer and right-sided colon cancer and the mechanism differences between the colorectal cancer core drug pairs of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba acting on left-sided and right-sided colon cancer.Methods The transcriptome data of 134 patients with left-sided colon cancer and 194 patients with right-sided colon cancer from The Cancer Genome Atlas(TCGA)were downloaded,and the R software was applied to realize the differential gene analysis of the two groups and the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway;the BATMAN-TCM database was used to obtain the active ingredients and targets of the drug pair of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba,and based on the different genes of the left-and right-sided colon cancers,KEGG enrichment analysis of the drug pair-left/right-sided colon cancers was performed respectively,and the protein-protein-interaction(PPI)network was constructed to compare the differences of the biosignaling pathways enriched by the drug pairs for the treatment of left-and right-sided colon cancers,as well as the differences of the key target points.Results There were 6 051 differentially expressed genes common to left-and right-sided colon cancers relative to normal paracancerous tissues,1958 differentially expressed genes specific to left-sided colon cancer,and 1739 differentially expressed genes specific to right-sided colon cancer;14 KEGG-enriched pathways specific to left-sided colon cancer,and 23 KEGG-enriched pathways specific to right-sided colon cancer.There were 85 active compounds in the drug-pair of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba,corresponding to a total of 469 targets.The drug-pair-left-sided colon cancer targets were enriched in 10 KEGG signaling pathways,with the key targets being DRD2,CACNA1C,HTR3A,COMT,and TH;and the drug-pair-right-sided colon cancer targets were enriched in 1 KEGG signaling pathway,with the core targets being HTR3A,DRD2 TH,AGT,GRIN2B.Conclusion There are gene expression differences between left-and right-sided colon cancers:left-sided colon cancer is associated with abnormal immune function,abnormal AMPK signaling pathway and other mechanisms,and right-sided colon cancer is associated with neutrophil extracellular trap formation,alcoholism,abnormal Hippo signaling pathway and other mechanisms.In addition to regulating cell cycle and essential amino acid metabolism and other mechanisms,Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba drug pairs have specific effects on regulating the intestinal endocrine function of the left-sided colon cancer,inhibiting inflammatory response of the right-sided colon cancer,and may also have mood-regulating effects on patients with colon cancer.
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Objective To investigate the genetic risk factors of deep vein thrombosis(DVT)after trauma.Methods In a nested case-control study,50 patients with DVT after traumatic lower extremity fractures and 50 patients without DVT were recruited.The two groups were matched with gender,age and fracture sites.Preoperative venography was performed to diagnose DVT in trauma patients.Genome wide association study(GWAS)was used to investigate the genetic risk factors for preoperative DVT after traumatic lower ex-tremity fractures.Genomic DNA in leukocytes from blood sample was extracted and used for GWAS.Results GWAS was conducted based on 2 662 single nucleotide variants(SNV)which were dispersed in 144 interested genes.Ten genes were found to have signifi-cant association with trauma-related DVT,including cofactors of hemostasis mechanism,i.e.,THBD,F5,SERPIND1 and ITGA2,the factors related to vitamin K-dependent(VKD)carboxylation,i.e.,GGCX and CALU,and the members of cytochrome P450 family,i.e.,CYP1A1,CYP3A4,CYP2C19 and CYP2B6.Conclusion DVT after trauma might be regulated by the cofactors of hemostasis mechanism,the factors related to VKD carboxylation and the members of cytochrome P450 family.The results of our study may provide reference and inspiration for genetic susceptibility of preoperative DVT after trauma.
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ObjectiveTo establish a rapid method for evaluating the heterozygosity of Murraya paniculata germplasm materials and provide as a foundation for developing germplasm breeding and innovation measures for M. paniculata. MethodSingle nucleotide polymorphisms （SNPs） were screened from the genome resequencing data of 65 plants of M. paniculata. A self-written script was used to transform 20 SNPs into restriction fragment length polymorphism （RFLP） markers. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） was employed to detect the 20 RFLP markers in 12 M. paniculata germplasm accessions， and the heterozygosity of M. paniculata germplasm accessions was calculated based on the number of enzyme-cutting bands at the 20 RFLP marker sites. Plink was used to calculate the whole genome heterozygosity of 12 M. paniculata germplasm accessions， and the results obtained with different methods were compared. ResultThere was no significant difference in the heterozygosity calculated by the PCR-RFLP method and the genome resequencing method. The PCR-RFLP and genome resequencing methods identified 8 and 9 germplasm accessions， respectively， with a heterozygosity level less than 30%. Seven germplasm accessions with heterozygosity less than 30.00% were calculated by both methods. ConclusionThe PCR-RFLP method established in this study for evaluating the heterozygosity of M. paniculata germplasm demonstrates the precision of 87.5% and the accuracy of 77.8%. This method serves as a reference for developing heterozygosity evaluation methods in other medicinal plant germplasm resources.
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Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.
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The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.
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The aim of this study was to investigate the virulence determinants and genetic diversity of foodborne Yersinia enterocolitica from Wenzhou.A total of 71 strains of Yersinia enterocolitica were isolated from food and foodborne diarrhea ca-ses in Wenzhou,and their biotypes,serotypes,and drug resistance were analyzed.On the basis of whole genome sequencing,we assessed virulence gene profiles,and performed multilocus sequence typing(MLST)and core gene multilocus sequence typ-ing(cgMLST).A total of 94.4％(67/71)of isolates belonged to biotype 1A,and the highest proportion had serotype lA/O∶5(29.6％,21/71).The sensitivity rates of the isolates to 14 antibiotics exceeded 95.8％.A total of 16 categories and 126 viru-lence genes were identified,with two strains carrying the pYV plasmid and chromosome-related virulence genes.ST3(31.6％,12/38)was the most widespread MLST type,and cgMLST analysis revealed no dense clusters of genotypes except for strains sharing the same ST.In conclusion,pathogenic strains were identified from foodborne Yersinia enterocolitica in Wenzhou and were found to exhibit high genetic polymorphism.Enhanced regulatory supervision is essential to prevent the outbreak of food-borne diseases caused by Yersinia enterocolitica.
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To perform a comprehensive analysis of the pathogenic causes of a food poisoning case in a district of Wuhan Cit-y,we investigated the molecular epidemiological relationships among pathogenic bacteria,to aid in traceability analysis of food-borne disease outbreaks,as well as clinical diagnosis and treatment.The pathogenic bacteria in this food poisoning case were i-solated and identified according to GB789.4-2016.The isolated strains were subjected to genotyping with pulsed field gel elec-trophoresis(PFGE).Drug resistance gene analysis,multi-locus sequence typing(MLST),and genome-wide single-nucleotide polymorphism analysis(wgSNP)were conducted via whole genome sequencing(WGS).The evolutionary tree for cluster analy-sis was constructed in fasttree software.Drug susceptibility testing was conducted with the broth microdilution method.A total of 12 strains of Salmonella were detected in seven anal swab samples and two fecal samples from the case,as well as three anal swab samples from unaffected individuals.The serotype of the strains was Salmonella typhimurium.The strain exhibited severe multiple drug resistance,including resistance to amikacin,ampi-cillin,cefazolin,gentamicin,piperacillin,and tetracycline,but susceptibility to other antibiotics.The coincidence rate between drug resistance genes and drug resistance phenotypes was high.PFGE revealed that nine strains from this food poisoning case were highly homologous.WGS revealed that the MLST type was ST19,and varying numbers of SNPs(1-6)were present a-mong strains.The phylogenetic tree revealed nine isolated strains forming a distinct cluster,differing from other Salmonella strains in the database and belonging to a novel clonal branch.The single nucleotide site in the strains was highly homologous to that of GCF in Jiangxi_020221795.1.The food poisoning case was caused by Salmonella typhimurium ST19,and all nine iso-lated strains originated from the same source.The chef is closely connected to this food poisoning case.This strain of Salmo-nella typhimurium belongs to a new clonal branch and exhibits multiple drug resistance.
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Objective Because of the poor prognosis of colon adenocarcinoma(COAD),it is necessary to screen prognosis-related genes in COAD patients and establish a new prognostic risk assessment model.Methods COAD-related data from the cancer genome atlas(TCGA)and gene expression omnibus(GEO)were used as training and validation sets,respectively.Weighted gene co-expression network analysis(WGCNA),a Cox regression model and least absolute selection and shrinkage operator(LASSO)regression analysis were used to screen prognosis-related genes of COAD and establish a prognostic model.A receiver operating characteristic(ROC)curve was combined with a survival curve to verify the model accuracy,and a nomogram was constructed.Patients were divided into two groups by the median risk score.The immune cell proportion score(IPS)was used to evaluate the immunotherapy response of the two groups.Results A total of 15 feature genes were screened.The area under the ROC curve in the predictive model of COAD patients was＞0.6,and the survival rate of the high-risk group was significantly lower than that of the low-risk group(P＜0.05),suggesting a good distinguishing ability for high-and low-risk COAD patients.Patients in the low-risk group had a higher IPS(P=0.026),indicating a better response to immunotherapy.Conclusions The model developed for COAD in this study has a good ability to predict the survival of patients at high and low risk of COAD.
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Objective:To study the expression and prognostic impact of secretory carrier membrane protein 3 (SCAMP3) in hepatocellular carcinoma (HCC) and its gene set enrichment analysis.Methods:SCAMP3 expression and its prognosis were analyzed using The Cancer Genome Atlas (TCGA) database. The cancer tissue and paracancerous tissue were collected from four patients with HCC undergoing surgery in Lishui Central Hospital to detect the expression of SCAMP3. Based on TCGA database, univariate and multivariate Cox regression was performed to analyze the relevance of SCAMP3 with prognosis of HCC. Gene set enrichment analysis was utilized to clarify the biological role of SCAMP3.Results:In TCGA database, SCAMP3 expression was higher in HCC tissues than that in normal liver tissues ( Z=-8.38, P<0.001). Patients were divided into the low-expression group ( n=185) and high-expression group ( n=185) based on the median SCAMP3 expression, and the overall survival rate was lower in patients with high SCAMP3 expression. In our four patients. The expression of SCAMP3 mRNA and protein in cancer tissues was higher than that in paracancerous tissues ( t=8.55, 6.24, both P<0.001). In multivariate Cox regression analysis, the higher SCAMP3 expression was associated with a higher risk of death ( HR=1.466, 95% CI: 1.143-1.881, P<0.001). Gene set enrichment analysis in patients with high SCAMP3 expression, the coagulation cascade and three signaling pathways involving the complements, retinol metabolism, and peroxisome proliferator-activated receptor were identified. Conclusion:SCAMP3 expression elevated in HCC, patients with a higher expression of SCAMP3 might have a worse prognosis. High SCAMP3 expression is a risk factor for the survival of patients with HCC. High SCAMP3 expression is associated with the coagulation cascade and the complements, retinoid metabolism, and peroxisome proliferator-activated receptor pathways.
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@#Objective To analyze the whole genome sequence and genetic characteristics of the Yunnan isolate of Coxsackievirus A8(CVA8),A8-1/YN/CHN/2019,in order to understand the prevalence and variation of CVA8.Methods The primers for CVA8 were designed,the viral RNA was extracted,the VP1 sequence was amplified by RT-PCR and sequenced,and the whole genome was spliced using BioEdit 7.2.3. MEGA 7.0 software was used for the phylogenetic analysis,and Simplot 3.5.1 and RDP4 software were used for the recombination analysis.Results Strain A8-1/YN/CHN/2019 was7 396 nt long and encoded 2 188 amino acids. The homologies of nucleotide and amino acid sequences between VP1 and CVA8 prototype strain AF081299/Donovan/USA/1998 were 81. 04% and 95. 24%,respectively. Strain A8-1/YN/CHN/2019 belonged to genotype E,while the other Chinese isolates were located in genotypes D and E. Recombination analysis revealed that strain A8-1/YN/CHN/2019 recombined on segments P2 and P3 of the non-structural coding region.Conclusion Strain A8-1/YN/CHN/2019 is of genotype E and has recombination events in the non-structural regions of the P2 and P3 segments.
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ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Jieyu Formula （左归降糖解郁方， ZJJF） for diabetic rats with depression. MethodsSixty rats were randomly divided into normal group， model group， wingless MMTV integration site family member 5a （Wnt5a） agonist group， ZJJF group， and ZJJF plus Wnt5a inhibitor group， with 12 rats in each group. Except for the normal group， the rats were fed with high-fat chow， streptozotocin injection， and chronic mild unpredictable stress combination， to establish model of diabetes mellitus complicated with depression. After successful modelling， rats in the Wnt5a agonist group were given bilateral hippocampal stereotactic injections of Wnt5a agonist Foxy-5 with 5 μl each for 7 consecutive days； rats in ZJJF group were given 20.52 g/（kg·d） of ZJJF by gavage； rats in ZJJF plus Wnt5a inhibitor group were given the drug by gavage， and bilateral hippocampal stereotactic injections of Wnt5a inhibitors Box5， with the same dosage and injection method as above. The normal group and model group were given 10 ml/（kg·d） of normal saline by gavage. All groups were gavaged for 4 consecutive weeks. At the end of the intervention， the depression-like behaviour of rats was evaluated using the forced swimming experiment （immobility time） and the absent field experiment （number of activities）； the blood glucose and insulin levels of rats were measured and the insulin resistance index was calculated； the dendritic morphology of dentate gyrus neurons in the hippocampus was observed using Golgi staining； the level of dentate gyrus neuron proliferation was measured using 5-bromodeoxyuracil nucleoside （Brdu） injection and immunofluorescence； RT-qPCR and Western blot were used to detect the mRNA and protein expression of Wnt5a， Ras homologue genomic member A （RhoA） and Rho homologue-associated coiled-coil protein kinase 1 （ROCK1） in the dentate gyrus. ResultsCompared with the normal group， rats in the model group had significantly higher blood glucose， insulin and insulin resistance indices， longer immobility time， fewer activities， lower Brdu integral optical density values and Wnt5a， RhoA， ROCK1 protein and mRNA expression in the dentate gyrus of the hippocampus （P＜0.05 or P＜ 0.01）； the dendritic branches of rat hippocampal dentate gyrus neurons could be seen to be significantly reduced or broken， and their length shortened. Compared with the model group， the blood glucose， insulin and insulin resistance indices of rats in ZJJF group and the ZJJF plus Wnt5a inhibitor group significantly reduced （P＜0.05 or P＜0.01）； the immobility time of rats in the Wnt5a agonist group and ZJJF group was significantly shortened， the number of activities increased， the Brdu integral optical density values elevated， and the Wnt5a， RhoA， ROCK1 protein and mRNA expression elevated （P＜0.05 or P＜0.01）， and the number of dendritic branches of hippocampal dentate gyrus neurons significantly increased， the length lengthened， and the complexity of dendrites increased. Compared with the Wnt5a agonist group， rats in the ZJJF group showed significant decrease in blood glucose， insulin and insulin resistance indices， prolongation of immobilisation time， reduction in the number of activities， and reduction in the Brdu integral optical density value； except for the Wnt5a mRNA in ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression reduced in both ZJJF group and ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. Compared with ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression were reduced in ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. ConclusionZJJF can improve hyperglycemia and depressive-like behaviours in rat models of diabetes with depression， and its antidepressant effects may be related to the activation of hippocampal Wnt5a/RhoA signaling and promotion of dentate gyrus neuron dendritic growth.
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【Objective】 To analyze the association between copper death-related genes and prognosis of prostate cancer and immune cell infiltration based on the cancer genome atlas (TCGA). 【Methods】 The mRNA transcriptome data of all prostate cancer patients were downloaded from TCGA, including 501 prostate cancer tissues and 52 normal tissues.The expression matrix of copper death-related genes was extracted with R software.Differential analysis and multivariate regression analysis were conducted to screen out the prognostic genes, which were then analyzed to explore the correlation between prognosis-related genes and immune cells. 【Results】 GCSH gene was significantly correlated with the prognosis of prostate cancer, and significantly correlated with dendritic cells, CD8+ T cells and plasma cells (P<0.05). 【Conclusion】 GCSH gene plays an important role in the occurrence and development of prostate cancer, and may become a prognostic marker of the disease.
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【Objective】 To investigate the effects of emotions (subjective well-being, depressed effect, worry, and guilt) on cancer (colorectal cancer, hepatic cancer, thyroid cancer, lung cancer, and breast cancer). 【Methods】 Two-sample bi-directional Mendelian randomization (MR) method was adopted. All data were based on summary data from genome-wide association studies (GWAS). Inverse variance weighting (IVW) was used to generate the main results, and weighted median (WM) and MR-Egger methods were employed to calculate supplementary results. The outcome measure was odds ratio (OR), and sensitivity analysis was conducted. 【Results】 For depressed effect, a significant association with lung cancer (OR=1.005, 95% CI: 1.001-1.009, P=0.015) was found. For worry, a significant association with breast cancer (OR=1.199, 95% CI: 1.011-1.423, P=0.038) was observed. For guilt, a significant association with thyroid cancer (OR=2.083, 95% CI: 1.080-4.017, P=0.029) was identified. After removing all potentially pleiotropic SNPs detected by MR PRESSO, the association between worry and breast cancer showed no statistical difference (P=0.064), while the association between worry and colorectal cancer remained significant (OR=0.739, 95% CI: 0.571-0.956, P=0.021). No causal relationship was found between cancer and emotions. 【Conclusion】 There is a causal relationship between depression and increased lung cancer incidence, guilt and increased thyroid cancer incidence, as well as anxiety and decreased colorectal cancer incidence.
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【Objective】 To explore the causal relationship between education level and pancreatitis risk through Mendelian randomization. 【Methods】 A two-sample Mendelian randomization analysis was conducted using genome-wide association study (GWAS) summary data. The GWAS data for education level and pancreatitis were obtained from SSGAC database and the FinnGen database (version R9). Causal relationship between education level and pancreatitis was explored using the inverse variance weighted (IVW), MR-Egger, and weighted median methods. Heterogeneity and directional pleiotropy were evaluated using Cochran’s Q test and funnel plots. 【Results】 Totally 604 SNPs associated with education level were included. The results provided evidence that there was negative relationship between education level and pancreatitis risk. For acute pancreatitis, OR=0.52, 95% CI: 0.44-0.62, P=2.43×10-14 while for chronic pancreatitis, OR=0.51, 95% CI: 0.41-0.64, P=7.20×10-9. Results from MR-Egger and weighted median analyses obtained the same results. The results of sensitivity analysis indicated that this study did not violate the basic assumptions of Mendelian randomization. 【Conclusion】 There is a causal relationship between education level and the occurrence of pancreatitis. The educational level is negatively correlated with the risk of pancreatitis.
ABSTRACT
【Objective】 To investigate the expression of optineurin (OPTN) in multiple myeloma (MM) and explore the mechanism and clinical value of OPTN gene in the occurrence and development of MM. 【Methods】 In this study, three gene expression omnibus (GEO) data sets were used to analyze the expression level of OPTN in MM. Clinical bone marrow samples of MM patients were collected. qRT-PCR was used to further verify the expression of OPTN in MM patients. The Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve were used to analyze the value of OPTN in the prognosis and diagnosis of MM. At the same time, MM transcriptome data were downloaded from the Cancer Genome Atlas (TCGA) database. According to the median boundary of OPTN mRNA expression level, the MM patients were divided into OPTN high- and low-expression groups. In order to investigate the possible molecular mechanisms of OPTN in MM, gene set enrichment analysis (GSEA) was made after the differentially expressed genes were filtered using the limma package of the R language. 【Results】 The expression level of OPTN was significantly lower in MM tissues than in normal tissues (P<0.05). OPTN expression level was significantly correlated with International Staging System (ISS) in MM patients (P<0.05). ROC results showed that the expression level of OPTN could distinguish between normal and MM patients. Survival analysis showed that the overall survival (OS) of patients with low OPTN expression was significantly lower than that of patients with high OPTN expression (P<0.05). GO, KEGG and GSEA enrichment analyses indicated that OPTN might affect apoptosis and autophagy, and regulate cellular immune response by regulating Nod-like receptors, NF-κB, TNF and RAS/MAPK pathways. 【Conclusion】 Low expression of OPTN in MM is associated with poor prognosis of patients, and thus may be an important potential biomarker for the diagnosis and treatment of MM.