Differential expression of bcl-2 and bax genes during the E.coli-induced apoptosis of human U937 cells

To explore the role of bcl-2 and bax genes in the apoptosis of human U937 cells induced by E.coli, flow cytometry assay with annexinⅤ-FITC/PI double staining was used to determine the condition of apoptosis, and the expressions of mRNA of bcl-2 and bax genes were assayed with RT-PCR. It was found that the apoptosis of human U937 cells could be induced by E.coli at various concentration ratios between cells and bacteria for 30 min in a dose-dependent manner. The apoptotic rates at cell/bacteria ratios of 0, 1∶5, 1∶10, 1∶20, 1∶50 and 1∶100 were 3.16%±0.90%, 9.46%±0.84%, 17.90%±1.41%, 35.59%±3.76%, 38.35%±7.12% and 55.07%±5.82% respectively. Also, there was a tendency of alterations in the expression levels of bcl-2 and bax genes with an increased expression level of bax gene and a reduced expression level of bcl-2 gene. It is concluded that E.coli can induce apoptosis in human U937 cells with a down-regulated expression of Bcl-2 and an up-regulated expression of Bax, and this might be related to the induction of apoptosis of the infected cell.

Exploring the modulatory role of bovine lactoferrin on the microbiome and the immune response in healthy and Shiga toxin‑producing E.coli challenged weaned piglets

Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial resistance.Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated.Lactoferrin has shown promising results against porcine enterotoxigenic E.coli strains,both in vitro and in vivo.Results We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned piglets.Additionally,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E.coli(STEC)infection.Therefore,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC strain.BLF did not affect theα-andβ-diversity.However,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa.When analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF group.Conclusion Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned piglets.Nevertheless,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut homeostasis.Furthermore,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.

Impact of an oligosaccharide-based polymer on the metabolic profiles and microbial ecology of weanling pigs experimentally infected with a pathogenic E.coli

Background Our previous study has reported that supplementation of oligosaccharide-based polymer enhances gut health and disease resistance of pigs infected with enterotoxigenic E.coli(ETEC)F18 in a manner similar to carbadox.The objective of this study was to investigate the impacts of oligosaccharide-based polymer or antibiotic on the host metabolic profiles and colon microbiota of weaned pigs experimentally infected with ETEC F18.Results Multivariate analysis highlighted the differences in the metabolic profiles of serum and colon digesta which were predominantly found between pigs supplemented with oligosaccharide-based polymer and antibiotic.The relative abundance of metabolic markers of immune responses and nutrient metabolisms,such as amino acids and carbohydrates,were significantly differentiated between the oligosaccharide-based polymer and antibiotic groups(q<0.2 and fold change>2.0).In addition,pigs in antibiotic had a reduced(P<0.05)relative abundance of Lachnospiraceae and Lactobacillaceae,whereas had greater(P<0.05)Clostridiaceae and Streptococcaceae in the colon digesta on d 11 post-inoculation(PI)compared with d 5 PI.Conclusions The impact of oligosaccharide-based polymer on the metabolic and microbial profiles of pigs is not fully understood,and further exploration is needed.However,current research suggest that various mechanisms are involved in the enhanced disease resistance and performance in ETEC-challenged pigs by supplementing this polymer.

Evaluating the Potential of Nitrofurantoin and Fosfomycin for E.coli UTIs: A Susceptibility Study

This study was designed to find the susceptibility of Nitrofurantoin and Fosfomycin among urinary isolates of Escherichia.coli.Four hundred(400)urine samples were collected for susceptibility of nitrofurantoin and fosfomycin among urinary isolates of E.coli.All indoor and outdoor patients'urinary samples yielded growth of E.coli.Mid-stream urine specimens were inoculated on blood agar and CLED agar and incubated at 35±2°C.Growth was observed,and Escherichia coli was identified by Gram staining,Catalase,Motility test and API 20E(Bio murex)as per standard procedure.Antimicrobial susceptibility testing of isolates for nitrofurantoin and fosfomycin was carried out by the modified Kirby-Bauer disc diffusion method according to CLSI guidelines ATCC 25922.E.coli was used as a quality control strain.A total of 400 samples were tested susceptibility of nitrofurantoin and fosfomycin among urinary isolates of E.coli during this period.A total of 400 samples yielded the growth of E.coli,out of which 178(44.5%)were male and 222(55.5%)were female samples.Among males,18(10%)were tolerant to nitrofurantoin,and 2(1.1%)were tolerant to fosfomycin.Among females,9(4.09%)were susceptible to nitrofurantoin while 6(2.72%)were susceptible to fosfomycin.Among age groups below 45 years old,6(4.76%)were tolerant to nitrofurantoin,and 2(1.58%)were sensitive to fosfomycin.Between 46-66 years old,4(2.81%)were sensitive to nitrofurantoin,and 3(2.11%)were sensitive to fosfomycin.Between 67-90 years old,17(12.87%)were sensitive to nitrofurantoin,and 4(3.03%)were tolerant to fosfomycin.Fosfomycin and nitrofurantoin showed good susceptibility in urinary isolates of E.coli and can be used empirically in our setup.

细胞学核评分结合BRAF V600E检测对BethesdaⅢ类甲状腺结节的诊断价值

目的:探讨细针穿刺细胞学(fine needle aspiration cytology,FNAC)意义未明确的非典型细胞(BethesdaⅢ)量化诊断标准,评估核评分结合BRAF V600E检测对BethesdaⅢ类甲状腺结节的诊断价值。方法:对124例原细胞学诊断为BethesdaⅢ类样本,重新经7个形态学指标核评分判读,并用免疫组化或荧光聚合酶链反应(polymerase chain reaction,PCR)法检测BRAF V600E突变。以核评分≥5分或BRAF V600E阳性判读为恶性,以组织学诊断或随访结果为诊断金标准。结果:42(42/124)例BethesdaⅢ类核评分≥5分,30(30/99)例BRAF V600E检测阳性,两种检测方法结合对124例甲状腺结节恶性的敏感度、特异度、阳性预测值、阴性预测值、恶性检出率分别为93.2%、95.0%、91.1%、96.2%、33.1%。结论:BethesdaⅢ类甲状腺结节有较高恶性风险率;核评分≥5分可作为区分甲状腺结节良性或乳头状癌的形态学量化域值,量化核评分可以大幅度减少BethesdaⅢ类的报告比率;核评分≥5分结合BRAF V600E检测,对甲状腺结节良恶性诊断有较高敏感度、特异度,并可提高其恶性检出率。

ACR-TIRADS和C-TIRADS单独及联合BRAF(V600E)基因检测对BethesdaⅢ/Ⅳ/Ⅴ类甲状腺结节的诊断效能比较

背景BethesdaⅢ/Ⅳ/Ⅴ类甲状腺结节的诊断一直是临床医师面临的挑战,BRAF(V600E)基因检测常用于术前评估,其特异度高,但敏感度低;美国放射学会和中华医学会超声分会分别提出了美国放射学会甲状腺影像报告和数据系统(American College of Radiology Thyroid Imaging Reporting and Data System,ACR-TIRADS)和中国甲状腺影像报告和数据系统(Chinese Thyroid Imaging Reporting and Data System,C-TIRADS);将TIRADS与BRAF(V600E)基因检测相结合,旨在提高BethesdaⅢ/Ⅳ/Ⅴ类结节的诊断率,并避免不必要的手术和穿刺活检。目的比较ACR-TIRADS与C-TIRADS对BethesdaⅢ/Ⅳ/Ⅴ类甲状腺结节的诊断效能,并探讨BARF(V600E)检测的附加价值。方法纳入2020年1月—2023年7月于解放军总医院第一医学中心接受细针穿刺活检并行BRAF(V600E)基因检测的484例患者(484个甲状腺结节),以病理组织学为“金标准”,比较ACR-TIRADS、C-TIRADS单独及联合BRAF(V600E)基因检测对BethesdaⅢ/Ⅳ/Ⅴ类甲状腺结节的诊断价值。结果两种超声分层系统中甲状腺结节的恶性风险随着分级的升高逐渐增加(趋势χ2检验,P均<0.001),ACR-TIRADS、C-TIRADS的最佳截断值分别为5类、4c类。BRAF(V600E)基因检测在不降低诊断特异度的基础上显著提高了ACR-TIRADS(0.809 vs 0.778,P<0.001)和C-TIRADS(0.815 vs 0.783,P<0.001)对BethesdaⅢ/Ⅳ/Ⅴ类甲状腺结节良恶性的诊断效能。ACR-TIRADS与C-TIRADS单独及联合BRAF(V600E)基因检测的曲线下面积(area under the curve,AUC)差异无统计学意义(0.778 vs 0.783,P=0.755;0.809 vs 0.815,P=0.675),但C-TIRADS单独及联合BRAF(V600E)基因检测的敏感度(88.83%vs 83.90%,P<0.001;95.33%vs 90.13%,P<0.001)和准确度(84.50%vs 81.41%,P<0.001;89.67%vs86.36%,P<0.001)高于ACR-TIRADS单独及联合诊断,而ACR-TIRADS单独及联合诊断的特异度相等,均高于C-TIRADS(71.72%vs 67.68%,P<0.001)。结论BRAF(V600E)基因检测可以在不降低特异度的基础上显著提高ACR-TIRADS、C-TIRADS对BethesdaⅢ/Ⅳ/Ⅴ类甲状腺结节良恶性的诊断性能,其中C-TIRADS单独及联合整体诊断性能最佳,在临床实践中具有一定的应用潜力。

Characteristics of β-Lactamase Synthesis in E. coli and K. pneumanie Strains in Nosocomial Infections

Background: Recently micro-organisms that synthesize extended-spectrum β-lactamase (ESBLs) were increased. The peculiarities of ESBL synthesis of Escherichia coli and Klebsiella pneumoniae strains that cause nosocomial urinary tract infections, surgical site infections and pneumonia in surgical clinic were studied. ESBL synthesis were observed 38.9% of E. coli strains obtained from urine, 92.3% of strains obtained from surgical site infections, and 50% of strains obtained from sputum. ESBL synthesis were observed 37.5% of K. pneumoniae strains obtained from urine, 85.7% of strains obtained from surgical site infections, and 60% of strains obtained from sputum. Different levels of ESBL synthesize of E. coli and K. pneumoniae strains isolated from different pattern is discussed. Conclusion. ESBL synthesis is common in E. coli and K. pneumoniae strains, which cause nosocomial infections. The frequency of occurrence of ESBL s synthesis among of these strains depends on clinical forms of nosocomial infections.

Preclinical and clinical evidence of the association of colibactinproducing Escherichia coli with anxiety and depression in colon cancer

BACKGROUND The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent.The gut microbiota contributes to colorectal carcinogenesis(CRC),as demonstrated with colibactin-producing Escherichia coli(CoPEC).AIM To evaluate the association between CoPEC prevalence and anxiety-and depressive-like behaviors with both preclinical and clinical approaches.METHODS Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview.Results were compared according to the CoPEC colonization.In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain.Their behavior was assessed using the Elevated Plus Maze test,the Forced Swimming Test and the Behavior recognition system PhenoTyper®.RESULTS In a limited cohort,all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis,whereas only one patient(17%)without CoPEC did.This result was confirmed in C57BL6/J wildtype mice and in a CRC susceptibility mouse model(adenomatous polyposis colimultiple intestinal neoplasia/+).Mice exhibited a significant increase in anxiety-and depressive-like behaviors after chronic infection with a CoPEC strain.CONCLUSION This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.

The virulence regulator AbsR in avian pathogenic Escherichia coli has pleiotropic effects on bacterial physiology

Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic E.coli(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and blood.MprA(microcin production regulation,locus A,herein renamed AbsR,a blood survival regulator),a member of the MarR(multiple antibiotic resistance regulator)transcriptional regulator family,governs the expression of capsule biosynthetic genes in human ExPEC and represents a promising druggable target for antimicrobials.However,a deep understanding of the AbsR regulatory mechanism as well as its regulon is lacking.In this study,we present a systems-level analysis of the APEC AbsR regulon using ChIP-Seq(chromatin immunoprecipitation sequencing)and RNA-Seq(RNA sequencing)methods.We found that AbsR directly regulates 99 genes and indirectly regulates 667 genes.Furthermore,we showed that:1)AbsR contributes to antiphagocytotic effects by macrophages and virulence in a mouse model for systemic infection by directly activating the capsular gene cluster;2)AbsR positively impacts biofilm formation via direct regulation of the T2SS(type II secretion system)but plays a marginal role in virulence;and 3)AbsR directly upregulates the acid tolerance signaling system EvgAS to withstand acid stress but is dispensable in ExPEC virulence.Finally,our data indicate that the role of AbsR in virulence gene regulation is relatively conserved in ExPEC strains.Altogether,this study provides a comprehensive analysis of the AbsR regulon and regulatory mechanism,and our data suggest that AbsR likely influences virulence primarily through the control of capsule production.Interestingly,we found that AbsR severely represses the expression of the type I-F CRISPR(clustered regularly interspaced short palindromic repeats)-Cas(CRISPR associated)systems,which could have implications in CRISPR biology and application.

Impact of apolipoprotein E isoforms on sporadic Alzheimer's disease:beyond the role of amyloid beta

The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully understood.ApoE exists as three common isoforms(ApoE2,ApoE3,and ApoE4),which differ in two amino acid residues.Traditionally,ApoE binds cholesterol and phospholipids and ApoE isoforms display diffe rent affinities for their receptors,lipids transport and distribution in the brain and periphery.The role of ApoE in the human depends on ApoE isoforms,brain regions,aging,and neural injury.APOE E4 is the strongest genetic risk factor for sporadic Alzheimer's disease,considering its role in influencing amyloid-beta metabolism.The exact mechanisms by which APOE gene variants may increase or decrease Alzheimer's disease risk are not fully understood,but APOE was also known to affect directly and indirectly tau-mediated neurodegeneration,lipids metabolism,neurovascular unit,and microglial function.Consistent with the biological function of ApoE,ApoE4 isoform significantly alte red signaling pathways associated with cholesterol homeostasis,transport,and myelination.Also,the rare protective APOE variants confirm that ApoE plays an important role in Alzheimer's disease pathogenesis.The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer's disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE,brain function,and memory,from a molecular to a clinical level.APOE genotype also exerted a heterogeneous effect on clinical Alzheimer's disease phenotype and its outcomes.Not only in learning and memory but also in neuro psychiatric symptoms that occur in a premorbid condition.Cla rifying the relationships between Alzheimer's disease-related pathology with neuropsychiatric symptoms,particularly suicidal ideation in Alzheimer's disease patients,may be useful for elucidating also the underlying pathophysiological process and its prognosis.Also,the effects of anti-amyloid-beta drugs,recently approved for the treatment of Alzheimer's disease,could be influenced by the APOE genotype.

Green Synthesis of Silver Nanoparticles Using Aqueous Orange and Lemon Peel Extract and Evaluation of Their Antimicrobial Properties

Green synthesis of silver nanoparticles (AgNPs) using aqueous extracts of orange and lemon peels, as a reducing agent, and silver nitrate salts as a source of silver ions is a promising field of research due to the versatility of biomedical applications of metal nanoparticles. In this paper, AgNPs were synthetized at different reaction parameters such as the type and concentration of the extracts, metal salt concentration, temperature, speed stirring, and pH. The antibacterial properties of the obtained silver nanoparticles against E. coli, as well as the physical and chemical characteristics of the synthesized silver nanoparticles, were investigated. UV-Vis spectroscopy was used to confirm the formation of AgNPs. In addition to green biogenic synthesis, chemical synthesis of silver nanoparticles was also carried out. The optimal temperature for extraction was 65˚C, while for the synthesis of AgNPs was 35˚C. The synthesis is carried out in an acidic environment (pH = 4.7 orange and pH = 3.8 lemon), neutral (pH = 7) and alkaline (pH = 10), then for different concentrations of silver nitrate solution (0.5 mM - 1 mM), optimal time duration of the reaction was 60 min and optimal stirring speed rotation was 250 rpm on the magnetic stirrer. The physical properties of the synthesized silver nanoparticles (conductivity, density and refractive index) were also studied, and the passage of laser light through the obtained solution and distilled water was compared. Positive inhibitory effect on the growth of new Escherichia coli colonies have shown AgNPs synthesized at a basic pH value and at a 0.1 mM AgNO3 using orange or lemon peel extract, while for a 0.5 mM AgNO3 using lemon peel extract.

Phytochemicals of Aloe barbadensis miller as Potential Inhibitors of Uropathogenic Escherichia coli for Urinary Tract Infection Therapy: An in Silico Approach

Urinary tract infections (UTIs) are common infections caused by normal skin or rectum bacteria that get into the urethra and infect the urinary tract. Although the infection can affect various parts of the tract, bladder infections are the most prevalent kind. Uropathogenic Escherichia Coli (UPEC) is the most common pathogen associated with UTI development. Therefore, inhibiting the UPEC protein target (PDB ID: 8BVD) appears to be a promising therapeutic strategy. Therefore, in this study, molecular docking and dynamics were conducted to examine the antibacterial activity of Aloe barbadensis miller against UPEC bacteria. The Aloe barbadensis miller natural compounds licochalcone A, palmidin B and palmidin C were downloaded from PubChem with amoxicillin, which was used as a control drug and studied against the target molecule. The potential parameters examined were the docking scores, absorption, distribution, metabolism, excretion, toxicity (ADMET), bioavailability, root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, radius of gyration, and potential energy of the system. Docking scores showed that all ligands demonstrated an admirable candidature as an inhibitor to 8BVD molecule, and the score hierarchy is licochalcone A (-6.4 kcal/mol), palmidin C (-6.1 kcal/mol), palmidin B (-6.0 kcal/mol), and amoxicillin (-5.9 kcal/mol). All ligands appeared to have good drug-like properties and oral bioavailability. Molecular dynamic studies showed that all ligands exhibited an excellent nominee as inhibitors in their vicinity at 20 ns. However, there is a relatively high fluctuation of palmidin B compared with other compounds, which seems to be more stable. This work suggests that the selected phytoconstituents could be used as inhibitors of the 8BVD protein in the fight against UTIs. However, further investigation on the clinical and experimental validation of UTI treatment’s specific mechanisms and effects is still welcomed.

The Transport and Persistence of Escherichia coli in Leachate from Poultry Litter Amended Soils

Fecal coliform bacteria such as Escherichia coli (E. coli) are one of the main sources of groundwater pollution. An assessment of the transport and Persistence of E. coli in poultry litter amended Decatur silty Clay soil and Hartsells Sandy soil was conducted using soil columns and simulated groundwater leaching. Enumeration of initial E. coli was determined to range from 2.851 × 103 to 3.044 × 103 CFU per gram of soil. These results have been used in a batch study to determine the persistence rate of E. coli in Decatur silty Clay soil and Hartsells Sandy soil. Results prove that E. coli survival growth rate increases for clay soil later than and at a higher rate than sandy soil. The column study has determined that E. coli was transported at a rate of 3.7 × 106 CFU for Decatur silty loam and 6.3 × 106 CFU for Hartsells sandy per gram of soil. Further, linear regression analysis predictions show higher porosity and soil moisture content affect transport, and Hartsells sandy soil has higher transport of E. coli due to its higher porosity and lower volumetric water content.

Retrospective study of the incidence, risk factors, treatment outcomes of bacterial infections at uncommon sites in cirrhotic patients

BACKGROUND Bacterial infections(BI)negatively affect the natural course of cirrhosis.The most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical variables.METHODS We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care center.BIs were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two groups.RESULTS In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical BI.Atypical BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage Liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the disease.Hence,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.

Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome

The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].

Correlation analysis of human papillomavirus E6/E7 mRNA detection with diagnosis,prognosis and recurrence risk in patients with cervical epithelioma

BACKGROUND Cervical intraepithelial neoplasia(CIN)is an important precursor of cervical cancer.Early detection and treatment can reduce the incidence of cervical cancer.AIM To investigate the detection rate of human papillomavirus(HPV)E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia(CIN)and its relationship with CIN progression and diagnosis.METHODS One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected.These patients were graded CIN based on colposcopy and cervical pathology.The positive expression rates of HPV E6/E7 mRNA and HPV[polymerase chain reaction(PCR)-reverse dot crossing]were compared among all groups.Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr.The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis.RESULTS The diagnostic sensitivity,specificity,and sensitivity of PCR-reverse point hybrid ization technology for secondary CIN were 70.41%,70.66%,and 0.714,respectively.Sensitivity and specificity for secondary CIN were 752%and 7853%,respectively,the area under the curve value was 0.789.Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I(P<0.05).In CIN grade I patients with positive for HPV E6/E7 mRNA,in its orientation to grade CIN patients,in its orientation to grade CIN patients,at 69.2%,compared with patients negative for HPV E6/E7 mRNA(30.8%),significant difference(P<0.05).CONCLUSION HPV E6/E7 mRNA and HPV(PCR-reverse dot hybrid)positive expression have a close relationship with CINgrade disease progression and is an independent risk factor for high-grade CIN lesions.

Decoding the Molecular Mechanisms of BRAFV600E-Induced Nevi Formation

Melanocytes derived from neural crest cells harbor the BRAFV600E mutation,which is the predominant driver of nevus formation in humans.This mutation leads to malignant cell proliferation and subsequent cell cycle arrest,culminating in oncogene-induced senescence and nevus development.Nevertheless,emerging evidence has highlighted the heterogeneity of cellular senescence markers in BRAFV600E-induced senescent melanocytes.Moreover,the capacity of melanocytes within nevi to regain their proliferative ability raises questions about the molecular mechanisms by which BRAFV600E,via the mitogen-activated protein kinase signaling pathway,triggers nevus formation.This study provides an overview and discussion of the molecular mechanisms underpinning BRAFV600E-induced melanocyte nevus formation and the relevant animal models employed for their elucidation.It also highlights the significance of elucidating dynamic changes in cytoplasmic and nuclear substrates that interact with phosphorylated extracellular signal-regulated protein kinases 1 and 2 and underscores the value of using targeted BRAFV600E animal models created through gene editing technologies.

Recent developments in immunotherapy approaches for allergic rhinitis

Allergic rhinitis(AR)poses a significant global health burden,with the potential to progress to asthma,thereby impacting patients’quality of life.Immunotherapy has demonstrated effectiveness in mitigating clinical symptoms by altering the underlying disease mechanisms of AR.This article provides a thorough review of the current state of immunotherapy for AR,encompassing various facets of immunotherapeutic strategies,elucidating their mechanisms and clinical implications.By presenting a nuanced understanding of the present landscape of immunotherapy for AR,this review aims to serve as a valuable reference for informing clinical treatment strategies.The subsequent analysis of diverse immunotherapeutic pathways offers a comprehensive understanding of their mechanisms and clinical implications.A meticulous examination is conducted on subcutaneous immunotherapy,sublingual immunotherapy,oral immunotherapy,intralymphatic immunotherapy,and innovative intravenous gold-induced autologous serum injection therapy.Each pathway is systematically elucidated,with its distinctive features and potential contributions to managing AR emphasized.In conclusion,synthesizing epidemiological insights,immunotherapeutic nuances,and pathway-specific analyses encapsulates a profound understanding of immunotherapy for AR.

Exploring the Latest Applications of OpenAI and ChatGPT: An In-Depth Survey

OpenAI and ChatGPT, as state-of-the-art languagemodels driven by cutting-edge artificial intelligence technology,have gained widespread adoption across diverse industries. In the realm of computer vision, these models havebeen employed for intricate tasks including object recognition, image generation, and image processing, leveragingtheir advanced capabilities to fuel transformative breakthroughs. Within the gaming industry, they have foundutility in crafting virtual characters and generating plots and dialogues, thereby enabling immersive and interactiveplayer experiences. Furthermore, these models have been harnessed in the realm of medical diagnosis, providinginvaluable insights and support to healthcare professionals in the realmof disease detection. The principal objectiveof this paper is to offer a comprehensive overview of OpenAI, OpenAI Gym, ChatGPT, DALL E, stable diffusion,the pre-trained clip model, and other pertinent models in various domains, encompassing CLIP Text-to-Image,education, medical imaging, computer vision, social influence, natural language processing, software development,coding assistance, and Chatbot, among others. Particular emphasis will be placed on comparative analysis andexamination of popular text-to-image and text-to-video models under diverse stimuli, shedding light on thecurrent research landscape, emerging trends, and existing challenges within the domains of OpenAI and ChatGPT.Through a rigorous literature review, this paper aims to deliver a professional and insightful overview of theadvancements, potentials, and limitations of these pioneering language models.

The efficacy of vitamin E in preventing arthrofibrosis after joint replacement

Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis.Methods:We simulated knee replacement in 16 male Sprague–Dawley rats.We immobilized the surgical leg with a suture in full flexion.The control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of arthrofibrosis.Immunofluorescent staining andα2-macroglobulin(α2M)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic inflammation.Static weight bearing(total internal reflection)and range of motion(ROM)were collected for functional assessment.Results:The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups.Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue.Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels.The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group.Conclusions:This model is viable for simulating arthrofibrosis after joint replacement.Vitamin E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.