Insulin resistance(IR)is widely recognized as a key contributor to metabolic disorders,and various surrogate indices have been developed to estimate IR in clinical and research settings.The hyperinsulinemic-euglycemic...Insulin resistance(IR)is widely recognized as a key contributor to metabolic disorders,and various surrogate indices have been developed to estimate IR in clinical and research settings.The hyperinsulinemic-euglycemic clamp is considered the gold standard method for assessing insulin resistance due to its precision;however,its complexity limits its widespread clinical application.Consequently,surrogate indices derived from fasting and post-load glucose and insulin levels have been developed to estimate IR,facilitating early detection and risk stratification in metabolic disorders.This mini-review discusses the clinical utility,strengths,and limitations of key IR indices,including the homeostasis model assessment of IR,quantitative insulin sensitivity check index,Matsuda index,and triglyceride-glucose index.Overall,the evidence presented to date suggests that these indices provide valuable estimates of IR in various popula-tions.Yet,their applicability varies depending on ethnic background,disease status,and clinical setting.Integrating these indices into routine clinical practice and research could improve metabolic risk assessment and guide preventive interventions.Further investigations are necessary to refine their accuracy and determine optimal cut-off values for various populations.展开更多
Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pa...Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenuated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model.Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens.Results:The attenuated EAE variant retains the standard hallmarks of neuroinflammation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by prophylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease.Conclusion:The new EAE variant is suitable for use in preclinical assessment of candidate therapeutics and the identification of targetable molecular mechanisms underpinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.展开更多
Abortion is one of the leading causes of maternal death in Cameroon, despite numerous policies and strategies put in place to reduce it by 2030.This study aims to describe the epidemiologic aspects of abortions within...Abortion is one of the leading causes of maternal death in Cameroon, despite numerous policies and strategies put in place to reduce it by 2030.This study aims to describe the epidemiologic aspects of abortions within hospitals in the city of Yaoundé in 2023. Methods: This was a descriptive cross-sectional study with prospective data collection in the maternity wards of the Yaoundé Gynaeco-Obstetric and Paediatric Hospital, and the Yaoundé Central Hospital for 7 months, from the 1st of November 2022 to the 31st of May 2023. The variables studied were demographic and clinical characteristics, means of recourse and post-abortion contraception. The frequency of abortions was calculated as the ratio of the number of abortions to the number of deliveries. The calculation of numbers and frequencies was used to describe the study population, and to highlight the sociodemographic and clinical characteristics of the patients recruited. Quantitative variables were expressed as mean ± standard deviation. Data were collected numerically and classified according to type, then analyzed using Epi-info version 7.2 software. Microsoft Office Excel 2013 was used to produce figures and tables. Results: During the study period, 169 patients were selected out of 1882 patients who had consulted for gynaecological emergencies;but only 164 of them accepted to participate. The frequency of abortions was 9.6% (169/1882). The age group of 25 to 29 years was the most represented, with 29.3% (48/164). They were mainly single 76.2% (125/164), and housewives 33.5% (55/164). The notion of previous abortion was found in 30.5% (50/164) of them. Approximately 19.5% of patients (32/164) reported to have conceived while using contraception, 56.2% of whom (18/32) used male condoms. At the time of admission to the emergency unit, the predominant symptom was bleeding in 70.7% of cases. The abortions were mainly spontaneous, in 75% of cases (123/164). In cases of induced abortions, 24.4% (10/41) of them took place after 14 weeks. Unexpected pregnancy was the main reason for termination in 46.3% of cases (19/41). Regarding induced abortion, 58.54% (24/41) of them resorted to voluntary medical termination. The mortality rate was 1.2%. The acceptability rate of a modern contraceptive method before discharge was 31.7%. Conclusion: Although frequent in our environment, data relating to abortion remain under-evaluated. Abortions occur mainly among young, single women, with a still very high proportion of induced abortions. The acceptability of post-abortion contraception remains poor. Prevention of unwanted pregnancies and risk factors is necessary to reduce the burden of abortions in low-income countries.展开更多
Objective:To investigate the therapeutic effect of trans-tarsal sinus approach surgery combined with dalteparin sodium and furosemide in the treatment of heel bone fracture.Methods:A hundred patients with heel bone fr...Objective:To investigate the therapeutic effect of trans-tarsal sinus approach surgery combined with dalteparin sodium and furosemide in the treatment of heel bone fracture.Methods:A hundred patients with heel bone fracture who were hospitalized from August 2023 to January 2025 were selected and randomly divided into two groups of 50 cases each.The control group was operated by purely trans-tarsal sinus approach,and the observation group added dalteparin sodium and furosemide on this basis.Postoperative limb swelling,pain,coagulation and inflammation indexes,fracture healing time,foot function and complications were compared between the two groups.Results:In the observation group,postoperative limb swelling subsided faster,pain score was lower,coagulation and inflammation indexes improved more significantly,fracture healing time was shorter,foot function recovery was better,and complication rate was lower,P<0.05.Conclusion:The treatment of heel fracture by trans-tarsal sinus approach combined with sodium heparin and furosemide can significantly accelerate the patient’s recovery and reduce the occurrence of complications,which has high clinical application value.展开更多
Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-cateni...Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.展开更多
Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen...Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen et al systematically evaluated six complete blood count-derived inflammatory indices:Neutrophil-tolymphocyte ratio,monocyte-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune-inflammation index,systemic inflammatory response index(SIRI),and aggregate index of systemic inflammation and demonstrated their positive associations with GU prevalence,identifying SIRI as the strongest predictor.This editorial contextualizes these findings within the broader literature,clarifies that these indices reflect systemic rather than GU-specific inflammation,highlights methodological strengths and major limitations,and proposes a conceptual clinical algorithm for integrating SIRI into GU risk assessment.Future multicenter studies incorporating Helicobacter pylori infection,non-steroidal antiinflammatory drug exposure,and prospective design are essential to validate and translate these findings into clinical practice.展开更多
Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinso...Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.展开更多
Background Our overall goal is to improve clinical care for inpatients with chronic heart failure(CHF).A retrospective assessment of CHF patients admitted to our hospital over the past decade(2005 vs.2014)indicated a ...Background Our overall goal is to improve clinical care for inpatients with chronic heart failure(CHF).A retrospective assessment of CHF patients admitted to our hospital over the past decade(2005 vs.2014)indicated a need for better strategies to evaluate clinical treatment,implement best practices and achieve optimal patient outcome.To that purpose,we developed a standardized plan to improve in-hospital treatment of acute decompensated CHF patients.Methods&Results Retrospective chart reviews were conducted to compare three cohorts of CHF patients admitted to the University Hospital of Lund at different time points over a 12-year period:2005(365 patients),2014(172 patients)and 2017-2018(57 patients).Little improvement was seen between 2005 and 2014 with respect to one-year mortality(35%vs.34%)and adequate treatment with recommended medications,e.g.,use of renin-angiotensin system blockers(45%vs.51%).A standardized treatment plan was devised to improve outcomes.A third cohort,treated under the plan(2017-2018),was compared with the 2014 cohort.One-year mortality(18%vs.34%)and 30-day readmission(5%vs.30%)were dramatically decreased,and adherence to medication guidelines was achieved.Key elements of the plan included well-defined treatment procedures,enhanced communication and teamwork,education,adequate time for treatment(5 days)and post-discharge follow-up as necessary.Natriuretic peptide(NT-proBNP)levels were useful for assessing patient status,prognosis and response to treatment.Conclusion Developmeof a standard plan for clinical management of acute decompensated CHF patients resulted in significant improvements in patient outcome,as reflected in decreased rates of 30-day readmission and one-year mortality.展开更多
Cholangiocarcinoma(CCC)is the most aggressive malignant tumor of the biliary tract.Perihilar CCC(pCCC)is the most common CCC and is burdened by a complicated diagnostic iter and its anatomical location makes surgical ...Cholangiocarcinoma(CCC)is the most aggressive malignant tumor of the biliary tract.Perihilar CCC(pCCC)is the most common CCC and is burdened by a complicated diagnostic iter and its anatomical location makes surgical approach burden by poor results.Besides its clinical presentation,a multimodal diagnostic approach should be carried on by a tertiary specialized center to avoid missdiagnosis.Preoperative staging must consider the extent of liver resection to avoid post-surgical hepatic failure.During staging iter,magnetic resonance can obtain satisfactory cholangiographic images,while invasive techniques should be used if bile duct samples are needed.Consistently,to improve diagnostic potential,bile duct drainage is not necessary in jaundice,while it is indicated in refractory cholangitis or when liver hypertrophy is needed.Once resecability criteria are identified,the extent of liver resection is secondary to the longitudinal spread of CCC.While in the past type IV pCCC was not considered resectable,some authors reported good results after their treatment.Conversely,in selected unresectable cases,liver transplantation could be a valuable option.Adjuvant chemotherapy is the standard of care for resected patients,while neoadjuvant approach has growing evidences.If curative resection is not achieved,radiotherapy can be added to chemotherapy.This multistep curative iter must be carried on in specialized centers.Hence,the aim of this review is to highlight the main steps and pitfalls of the diagnostic and therapeutic approach to pCCC with a peculiar attention to type IV pCCC.展开更多
Ulcerative colitis(UC)is a chronic inflammatory bowel condition characterised by a relapsing and remitting course.Symptom control has been the traditional mainstay of medical treatment.It is well known that histologic...Ulcerative colitis(UC)is a chronic inflammatory bowel condition characterised by a relapsing and remitting course.Symptom control has been the traditional mainstay of medical treatment.It is well known that histological inflammatory activity persists despite adequate symptom control and absence of endoscopic inflammation.Current evidence suggests that presence of histological inflammation poses a greater risk of disease relapse and subsequent colorectal cancer risk.New endoscopic technologies hold promise for developing endoscopic markers of mucosal inflammation.Achieving endoscopic and histological remission appears be the future aim of medical treatments for UC.This review article aims to evaluate the use of endoscopy as a tool in assessment of mucosal inflammation UC and its correlation with disease outcomes.展开更多
Autosomal dominant osteopetrosis type 2 (ADO2) is a high-density brittle bone disease characterized by bone pain,multiple fractures and skeletal-related events,including nerve compression syndrome and hematological fa...Autosomal dominant osteopetrosis type 2 (ADO2) is a high-density brittle bone disease characterized by bone pain,multiple fractures and skeletal-related events,including nerve compression syndrome and hematological failure.We demonstrated that in mice carrying the heterozygous Clcn7^G213R mutation,whose human mutant homolog CLCN7^G215R affects patients,the clinical impacts of ADO2 extend beyond the skeleton,affecting several other organs.The hallmark of the extra-skeletal alterations is a consistent perivascular fibrosis,associated with high numbers of macrophages and lymphoid infiltrates.Fragmented clinical information in a small cohort of patients confirms extra-skeletal alterations consistent with a systemic disease,in line with the observation that the CLCN7 gene is expressed in many organs.ADO2 mice also show anxiety and depression and their brains exhibit not only perivascular fibrosis but also β-amyloid accumulation and astrogliosis,suggesting the involvement of the nervous system in the pathogenesis of the ADO2 extra-skeletal alterations.Extra-skeletal organs share a similar cellular pathology,confirmed also in vitro in bone marrow mononuclear cells and osteoclasts,characterized by an impairment of the exit pathway of the Clcn7 protein product,ClC7,through the Golgi,with consequent reduced ClC7 expression in late endosomes and lysosomes,associated with high vesicular pH and accumulation of autophagosome markers.Finally,an experimental siRNA therapy,previously proven to counteract the bone phenotype,also improves the extra-skeletal alterations.These results could have important clinical implications,supporting the notion that a systematic evaluation of ADO2 patients for extra-skeletal symptoms could help improve their diagnosis,clinical management,and therapeutic options.展开更多
Fluctuations in autonomic cardiovascular regulation during exposure to high altitude may increase the risk of heart attack during waking and sleep. This study compared heart rate variability (HVR) and its components d...Fluctuations in autonomic cardiovascular regulation during exposure to high altitude may increase the risk of heart attack during waking and sleep. This study compared heart rate variability (HVR) and its components during sleep at low altitude and after 30 - 41 hours of acclimatization at high altitude (3480 m) in five mountain marathon runners controlled for diet, drugs, light-dark cycle and jet lag. In comparison to sea level, RR-intervals during sleep at high altitude decreased significantly (P 0.001). The significant increase in sympathetic autonomic cardiovascular modulation at high altitude protects against excessive oxygen deprivation during sleep. Increases in R-R intervals can require longer periods of acclimatization at3480 m to mitigate the effects of altitude/hypoxia on sympathetic tone, thus reducing cardiovascular distress at rest during waking and sleep and probably before during and after athletic performance at altitude.展开更多
Despite improvements in surgical techniques and adjuvant chemotherapy, the overall mortality rates in pan- creatic cancer have generally remained relatively un-changed and the 5-year survival rate is actually below 2%...Despite improvements in surgical techniques and adjuvant chemotherapy, the overall mortality rates in pan- creatic cancer have generally remained relatively un-changed and the 5-year survival rate is actually below 2%. This paper will address the importance of achieving an early diagnosis and identifying markers for prog- nosis and response to therapy such as genes, proteins, microP, NAs or epigenetic modifications. However, there are still major hurdles when translating investigational biomarkers into routine clinical practice. Furthermore, novel ways of secondary screening in high-risk individu- als, such as artificial neural networks and modern imaging, will be discussed. Drug resistance is ubiquitous in pancreatic cancer. Several mechanisms of drug resistance have already been revealed, including human equilibrative nucleoside transporter-1 status, multidrug resistance proteins, aberrant signaling pathways, mi-croRNAs, stromal influence, epithelial-mesenchymal transition-type cells and recently the presence of can- cer stem cells/cancer-initiating cells. These factors must be considered when developing more customized types of intervention （＇personalized medicine＇S. In the future, multifunctional nanoparticles that combine a specific targeting agent, an imaging probe, a cell-penetrating agent, a biocompatible polymer and an anti-cancer drug may become valuable for the management of pa- tients with pancreatic cancer.展开更多
AIM:To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA). METHODS:Sixty-nine ulcerative colitis patients (39 F,30 M) dependent upon/refractory to ...AIM:To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA). METHODS:Sixty-nine ulcerative colitis patients (39 F,30 M) dependent upon/refractory to steroids were treated with GMA. Steroid dependency,clinical activity index (CAI),C reactive protein (CRP) level,erythrocyte sedimentation rate (ESR),values at baseline,use of immunosuppressant,duration of disease,and age and extent of disease were considered for statistical analysis as predictive factors of clinical response. Univariate and multivariate logistic regression models were used. RESULTS:In the univariate analysis,CAI (P = 0.039) and ESR (P = 0.017) levels at baseline were singled out as predictive of clinical remission. In the multivariate analysis steroid dependency [Odds ratio (OR) = 0.390,95% Confidence interval (CI):0.176-0.865,Wald 5.361,P = 0.0160] and low CAI levels at baseline (4 < CAI <7) (OR = 0.770,95% CI:0.425-1.394,Wald 3.747,P = 0.028) proved to be effective as factors predicting clinical response. CONCLUSION:GMA may be a valid therapeutic option for steroid-dependent ulcerative colitis patients with mild-moderate disease and its clinical efficacy seems to persist for 12 mo.展开更多
Background:Mastitis caused by different pathogens including Streptococcus uberis(S.uberis)is responsible for huge economic losses to the dairy industry.In order to investigate the potential genetic and epigenetic regu...Background:Mastitis caused by different pathogens including Streptococcus uberis(S.uberis)is responsible for huge economic losses to the dairy industry.In order to investigate the potential genetic and epigenetic regulatory mecha‑nisms of subclinical mastitis due to S.uberis,the DNA methylome(whole genome DNA methylation sequencing)and transcriptome(RNA sequencing)of milk somatic cells from cows with naturally occurring S.uberis subclinical mastitis and healthy control cows(n=3/group)were studied.Results:Globally,the DNA methylation levels of CpG sites were low in the promoters and first exons but high in inner exons and introns.The DNA methylation levels at the promoter,first exon and first intron regions were nega‑tively correlated with the expression level of genes at a whole‑genome‑wide scale.In general,DNA methylation level was lower in S.uberis‑positive group(SUG)than in the control group(CTG).A total of 174,342 differentially methylated cytosines(DMCs)(FDR<0.05)were identified between SUG and CTG,including 132,237,7412 and 34,693 DMCs in the context of CpG,CHG and CHH(H=A or T or C),respectively.Besides,101,612 methylation haplotype blocks(MHBs)were identified,including 451 MHBs that were significantly different(dMHB)between the two groups.A total of 2130 differentially expressed(DE)genes(1378 with up‑regulated and 752 with down‑regulated expression)were found in SUG.Integration of methylome and transcriptome data with MethGET program revealed 1623 genes with signifi‑cant changes in their methylation levels and/or gene expression changes(MetGDE genes,MethGET P‑value<0.001).Functional enrichment of genes harboring≥15 DMCs,DE genes and MetGDE genes suggest significant involvement of DNA methylation changes in the regulation of the host immune response to S.uberis infection,especially cytokine activities.Furthermore,discriminant correlation analysis with DIABLO method identified 26 candidate biomarkers,including 6 DE genes,15 CpG‑DMCs and 5 dMHBs that discriminated between SUG and CTG.Conclusion:The integration of methylome and transcriptome of milk somatic cells suggests the possible involve‑ment of DNA methylation changes in the regulation of the host immune response to subclinical mastitis due to S.uberis.The presented genetic and epigenetic biomarkers could contribute to the design of management strategies of subclinical mastitis and breeding for mastitis resistance.展开更多
We investigated whether DNA fragmentation in two cytometric sperm populations （PIddimmer and PIbriehter） with different biological characteristics and clinical relevance is related to clinical and color-Doppler ultr...We investigated whether DNA fragmentation in two cytometric sperm populations （PIddimmer and PIbriehter） with different biological characteristics and clinical relevance is related to clinical and color-Doppler ultrasound （CDUS） parameters of the male genital tract. One hundred and sixty males of infertile couples without genetic abnormalities were evaluated for clinical, scrotal, and transrectal CDUS characteristics, presence of prostatitis-like symptoms （with the National Institutes of Health-Chronic Prostatitis Symptom Index） and sperm DNA fragmentation （sDF） in PIdimmer and PIbrighter populations （using TUNEIJPI method coupled with flow cytometry）. Data were adjusted for age （Model 1） along with waistline, testosterone levels, smoking habit, and sexual abstinence （Model 2）. According to the statistical Model 2, PIdi sDF was associated with testicular abnormalities, including lower clinical and ultrasound volume （r = -0.21 and r = -0.20, respectively; P 〈 0.05）, higher FSH levels （r = 0.34, P 〈 0.0001） and occurrence of testicular inhomogeneity （P 〈 0.05） and hypoechogenicity （P 〈 0.05）. PIbrighter sDF was associated with prostate-related symptoms and abnormal signs, including higher NIH-CPSI total and subdomain scores, a higher prevalence of prostatitis-like symptoms and of CDUS alterations such as macro-calcifications, severe echo-texture inhomogeneity, hyperemia （all P 〈 0.05）, and higher arterial peak systolic velocity （r = 0.25, P 〈 0.05）. Our results suggest that DNA fragmentation in PIdimmer sperm, which is related to poor semen quality, mainly originates in the testicles, likely due to apoptosis. Conversely, DNA fragmentation in PIbrighter sperm appears to mainly originate during or after transit through the prostate, increasing with the presence of an inflammatory status of the organ. These results could lead to new perspectives for the identification of therapeutic targets to reduce sDF.展开更多
Orthostatic hypertension(OHT)is a condition characterized by an increase in blood pressure after assuming the standing position.[1]Nowadays no consensus definition exists,thus OHT prevalence varies among studies(4%-20...Orthostatic hypertension(OHT)is a condition characterized by an increase in blood pressure after assuming the standing position.[1]Nowadays no consensus definition exists,thus OHT prevalence varies among studies(4%-20.3%).展开更多
Objective:To determine the genetic diversity,natural selection and mutations in Plasmodium(P.)knowlesi drug resistant molecular markers Kelch 13 and dhps gene in clinical samples of Malaysia.Methods:P.knowlesi full-le...Objective:To determine the genetic diversity,natural selection and mutations in Plasmodium(P.)knowlesi drug resistant molecular markers Kelch 13 and dhps gene in clinical samples of Malaysia.Methods:P.knowlesi full-length gene sequences Kelch 13 gene(PkK13)from 40 samples and dhps gene from 30 samples originating from Malaysian Borneo were retrieved from public databases.Genetic diversity,natural selection,and phylogenetic analysis of gene sequences were analysed using DNAsp v5.10 and MEGA v5.2.Results:Seventy-two single nucleotide polymorphic sites(SNPs)across the full-length PkK13 gene(63 synonymous substitutions and 9 non-synonymous substitutions)with nucleotide diversity ofπ~0.005 was observed.Analysis of the full-length Pkdhps gene revealed 73 SNPs andπ~0.006(44 synonymous substitutions and 29 non-synonymous substitutions).A high number of haplotypes(PkK13;H=37 and Pkdhps;H=29)with haplotype diversity of Hd~0.99 were found in both genes,indicating population expansion.Nine mutant alleles were identified in PkK13 amino acid alignment of which,7(Asp3Glu,Lys50Gln,Lys53Glu,Ser123Thr,Ser127Pro,Ser149Thr and Ala169Thr)were within the Plasmodium specific domain,2(Val372Ile and Lys424Asn)were in the BTB/POZ domain and no mutation was observed within the kelch propeller domain.The 29 non-synonymous mutations in the Pkdhps gene were novel and only presented in exon 1 and 2.Conclusions:Monitoring the mutations from clinical samples collected from all states of Malaysia along with clinical efficacy studies will be necessary to determine the drug resistance in P.knowlesi.展开更多
BACKGROUND Antinuclear antibodies(ANAs)are crucial in diagnosing autoimmune diseases,mainly systemic lupus erythematosus(SLE).This study aimed to compare the performance of chemiluminescence assay(CLIA)and line immuno...BACKGROUND Antinuclear antibodies(ANAs)are crucial in diagnosing autoimmune diseases,mainly systemic lupus erythematosus(SLE).This study aimed to compare the performance of chemiluminescence assay(CLIA)and line immunoassay(LIA)in detecting ANAs in patients with autoimmune diseases,evaluate their diagnostic accuracy for SLE,and develop a novel diagnostic model using CLIA-detected antibodies for SLE.Specimens from patients with autoimmune diseases and physical examination specimens were collected to parallel detect specific antibodies.Individual antibodies'diagnostic performance and a model combining multiple antibodies were assessed.The findings provide valuable insights into improving the diagnosis of SLE through innovative approaches.AIM To compare the performance of CLIA and LIA in detecting ANAs in patients with autoimmune diseases,assess their accuracy for SLE,and develop a novel diagnostic model using CLIA-detected antibodies for SLE.METHODS Specimens have been obtained from 270 patients with clinically diagnosed autoimmune disorders,as well as 130 physical examination specimens.After that,parallel detection of anti-double-stranded DNA(dsDNA)antibody,anti-histone(Histone)antibody,anti-nucleosome(Nuc)antibody,anti-Smith(Sm)antibody,anti-ribosomal P protein(Rib-P)antibody,anti-sicca syndrome A(Ro60)antibody,anti-sicca syndrome A(Ro52)antibody,anti-sicca syndrome(SSB)antibody,anticentromere protein B(Cenp-B)antibody,anti-DNA topoisomerase 1(Scl-70)antibody,anti-histidyl tRNA synthetase(Jo-1)antibody,and anti-mitochondrial M2(AMA-M2)antibody was performed using CLIA and LIA.The detection rates,compliance rates,and diagnostic performance for SLE were compared between the two methodologies,followed by developing a novel diagnostic model for SLE.RESULTS CLIA and LIA exhibited essentially comparable detection rates for anti-dsDNA antibody,anti-Histone antibody,anti-Nuc antibody,anti-Sm antibody,anti-Rib-P antibody,anti-Ro60 antibody,anti-Ro52 antibody,anti-SSB antibody,anti-Cenp-B antibody,anti-DNAScl-70 antibody,anti-Jo-1 antibody and anti-AMA-M2 antibody(P>0.05).The two methods displayed identical results for the detection of anti-dsDNA antibody,anti-Histone antibody,anti-Nuc antibody,anti-Sm antibody,anti-Ro60 antibody,anti-Ro52 antibody,anti-SSB antibody,anti-Cenp-B antibody,anti-Scl-70 antibody,and anti-AMA-M2 antibody(Kappa>0.7,P<0.05),but showed a moderate agreement for the detection of anti-Rib-P antibody and anti-Jo-1 antibody(Kappa=0.671 and 0.665;P<0.05).In addition,the diagnostic performance of these antibodies detected by both methods was similar for SLE.The diagnostic model's area under the curve values,sensitivity,and specificity,including an anti-dsDNA antibody and an anti-Ro60 antibody detected by CLIA,were 0.997,0.962,and 0.978,respectively.These values were higher than the diagnostic performance of individual antibodies.CONCLUSION CLIA and LIA demonstrated excellent overall consistency in detecting ANA profiles.A diagnostic model based on CLIA-detected antibodies can successfully contribute to developing a novel technique for detecting SLE.展开更多
Prostate cancer risk stratification relies on several clinical factors. Low-risk patients, characterized by T1–T2a stage, Gleason score (GS) ≤6, and prostate-specific antigen (PSA) <10 ng ml−1, exhibit an excelle...Prostate cancer risk stratification relies on several clinical factors. Low-risk patients, characterized by T1–T2a stage, Gleason score (GS) ≤6, and prostate-specific antigen (PSA) <10 ng ml−1, exhibit an excellent prognosis and are suitable for active surveillance (AS). Regular monitoring is essential for these patients, including PSA tests every 3–6 months, annual digital rectal exams (DRE), and prostate biopsies every 6–12 months, followed by less frequent biopsies every 2–5 years. Epstein criteria, which consider GS ≤6, PSA density (PSAD) <0.15 ng ml−2, limited tumor involvement in cores, and absence of high-risk features, help predict pathologic and biochemical relapse-free survival and guide AS management.展开更多
文摘Insulin resistance(IR)is widely recognized as a key contributor to metabolic disorders,and various surrogate indices have been developed to estimate IR in clinical and research settings.The hyperinsulinemic-euglycemic clamp is considered the gold standard method for assessing insulin resistance due to its precision;however,its complexity limits its widespread clinical application.Consequently,surrogate indices derived from fasting and post-load glucose and insulin levels have been developed to estimate IR,facilitating early detection and risk stratification in metabolic disorders.This mini-review discusses the clinical utility,strengths,and limitations of key IR indices,including the homeostasis model assessment of IR,quantitative insulin sensitivity check index,Matsuda index,and triglyceride-glucose index.Overall,the evidence presented to date suggests that these indices provide valuable estimates of IR in various popula-tions.Yet,their applicability varies depending on ethnic background,disease status,and clinical setting.Integrating these indices into routine clinical practice and research could improve metabolic risk assessment and guide preventive interventions.Further investigations are necessary to refine their accuracy and determine optimal cut-off values for various populations.
基金Private DonationLa Trobe Research Focus AreasMultiple Sclerosis Australia,Grant/Award Number:20-032。
文摘Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenuated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model.Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens.Results:The attenuated EAE variant retains the standard hallmarks of neuroinflammation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by prophylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease.Conclusion:The new EAE variant is suitable for use in preclinical assessment of candidate therapeutics and the identification of targetable molecular mechanisms underpinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.
文摘Abortion is one of the leading causes of maternal death in Cameroon, despite numerous policies and strategies put in place to reduce it by 2030.This study aims to describe the epidemiologic aspects of abortions within hospitals in the city of Yaoundé in 2023. Methods: This was a descriptive cross-sectional study with prospective data collection in the maternity wards of the Yaoundé Gynaeco-Obstetric and Paediatric Hospital, and the Yaoundé Central Hospital for 7 months, from the 1st of November 2022 to the 31st of May 2023. The variables studied were demographic and clinical characteristics, means of recourse and post-abortion contraception. The frequency of abortions was calculated as the ratio of the number of abortions to the number of deliveries. The calculation of numbers and frequencies was used to describe the study population, and to highlight the sociodemographic and clinical characteristics of the patients recruited. Quantitative variables were expressed as mean ± standard deviation. Data were collected numerically and classified according to type, then analyzed using Epi-info version 7.2 software. Microsoft Office Excel 2013 was used to produce figures and tables. Results: During the study period, 169 patients were selected out of 1882 patients who had consulted for gynaecological emergencies;but only 164 of them accepted to participate. The frequency of abortions was 9.6% (169/1882). The age group of 25 to 29 years was the most represented, with 29.3% (48/164). They were mainly single 76.2% (125/164), and housewives 33.5% (55/164). The notion of previous abortion was found in 30.5% (50/164) of them. Approximately 19.5% of patients (32/164) reported to have conceived while using contraception, 56.2% of whom (18/32) used male condoms. At the time of admission to the emergency unit, the predominant symptom was bleeding in 70.7% of cases. The abortions were mainly spontaneous, in 75% of cases (123/164). In cases of induced abortions, 24.4% (10/41) of them took place after 14 weeks. Unexpected pregnancy was the main reason for termination in 46.3% of cases (19/41). Regarding induced abortion, 58.54% (24/41) of them resorted to voluntary medical termination. The mortality rate was 1.2%. The acceptability rate of a modern contraceptive method before discharge was 31.7%. Conclusion: Although frequent in our environment, data relating to abortion remain under-evaluated. Abortions occur mainly among young, single women, with a still very high proportion of induced abortions. The acceptability of post-abortion contraception remains poor. Prevention of unwanted pregnancies and risk factors is necessary to reduce the burden of abortions in low-income countries.
文摘Objective:To investigate the therapeutic effect of trans-tarsal sinus approach surgery combined with dalteparin sodium and furosemide in the treatment of heel bone fracture.Methods:A hundred patients with heel bone fracture who were hospitalized from August 2023 to January 2025 were selected and randomly divided into two groups of 50 cases each.The control group was operated by purely trans-tarsal sinus approach,and the observation group added dalteparin sodium and furosemide on this basis.Postoperative limb swelling,pain,coagulation and inflammation indexes,fracture healing time,foot function and complications were compared between the two groups.Results:In the observation group,postoperative limb swelling subsided faster,pain score was lower,coagulation and inflammation indexes improved more significantly,fracture healing time was shorter,foot function recovery was better,and complication rate was lower,P<0.05.Conclusion:The treatment of heel fracture by trans-tarsal sinus approach combined with sodium heparin and furosemide can significantly accelerate the patient’s recovery and reduce the occurrence of complications,which has high clinical application value.
基金financially supporting this work through the Large Research Group Project under Grant no.R.G.P.2/509/45
文摘Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.
基金Supported by the National Natural Science Foundation of China,No.82170406 and No.81970238.
文摘Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen et al systematically evaluated six complete blood count-derived inflammatory indices:Neutrophil-tolymphocyte ratio,monocyte-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune-inflammation index,systemic inflammatory response index(SIRI),and aggregate index of systemic inflammation and demonstrated their positive associations with GU prevalence,identifying SIRI as the strongest predictor.This editorial contextualizes these findings within the broader literature,clarifies that these indices reflect systemic rather than GU-specific inflammation,highlights methodological strengths and major limitations,and proposes a conceptual clinical algorithm for integrating SIRI into GU risk assessment.Future multicenter studies incorporating Helicobacter pylori infection,non-steroidal antiinflammatory drug exposure,and prospective design are essential to validate and translate these findings into clinical practice.
基金financially supported by King Abdulaziz University,Deanship of Scientific Research(DSR)。
文摘Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.
文摘Background Our overall goal is to improve clinical care for inpatients with chronic heart failure(CHF).A retrospective assessment of CHF patients admitted to our hospital over the past decade(2005 vs.2014)indicated a need for better strategies to evaluate clinical treatment,implement best practices and achieve optimal patient outcome.To that purpose,we developed a standardized plan to improve in-hospital treatment of acute decompensated CHF patients.Methods&Results Retrospective chart reviews were conducted to compare three cohorts of CHF patients admitted to the University Hospital of Lund at different time points over a 12-year period:2005(365 patients),2014(172 patients)and 2017-2018(57 patients).Little improvement was seen between 2005 and 2014 with respect to one-year mortality(35%vs.34%)and adequate treatment with recommended medications,e.g.,use of renin-angiotensin system blockers(45%vs.51%).A standardized treatment plan was devised to improve outcomes.A third cohort,treated under the plan(2017-2018),was compared with the 2014 cohort.One-year mortality(18%vs.34%)and 30-day readmission(5%vs.30%)were dramatically decreased,and adherence to medication guidelines was achieved.Key elements of the plan included well-defined treatment procedures,enhanced communication and teamwork,education,adequate time for treatment(5 days)and post-discharge follow-up as necessary.Natriuretic peptide(NT-proBNP)levels were useful for assessing patient status,prognosis and response to treatment.Conclusion Developmeof a standard plan for clinical management of acute decompensated CHF patients resulted in significant improvements in patient outcome,as reflected in decreased rates of 30-day readmission and one-year mortality.
文摘Cholangiocarcinoma(CCC)is the most aggressive malignant tumor of the biliary tract.Perihilar CCC(pCCC)is the most common CCC and is burdened by a complicated diagnostic iter and its anatomical location makes surgical approach burden by poor results.Besides its clinical presentation,a multimodal diagnostic approach should be carried on by a tertiary specialized center to avoid missdiagnosis.Preoperative staging must consider the extent of liver resection to avoid post-surgical hepatic failure.During staging iter,magnetic resonance can obtain satisfactory cholangiographic images,while invasive techniques should be used if bile duct samples are needed.Consistently,to improve diagnostic potential,bile duct drainage is not necessary in jaundice,while it is indicated in refractory cholangitis or when liver hypertrophy is needed.Once resecability criteria are identified,the extent of liver resection is secondary to the longitudinal spread of CCC.While in the past type IV pCCC was not considered resectable,some authors reported good results after their treatment.Conversely,in selected unresectable cases,liver transplantation could be a valuable option.Adjuvant chemotherapy is the standard of care for resected patients,while neoadjuvant approach has growing evidences.If curative resection is not achieved,radiotherapy can be added to chemotherapy.This multistep curative iter must be carried on in specialized centers.Hence,the aim of this review is to highlight the main steps and pitfalls of the diagnostic and therapeutic approach to pCCC with a peculiar attention to type IV pCCC.
文摘Ulcerative colitis(UC)is a chronic inflammatory bowel condition characterised by a relapsing and remitting course.Symptom control has been the traditional mainstay of medical treatment.It is well known that histological inflammatory activity persists despite adequate symptom control and absence of endoscopic inflammation.Current evidence suggests that presence of histological inflammation poses a greater risk of disease relapse and subsequent colorectal cancer risk.New endoscopic technologies hold promise for developing endoscopic markers of mucosal inflammation.Achieving endoscopic and histological remission appears be the future aim of medical treatments for UC.This review article aims to evaluate the use of endoscopy as a tool in assessment of mucosal inflammation UC and its correlation with disease outcomes.
基金supported by the Fondazione Telethon Grants GGP09018 and GGP14014the European Union funded project SYBIL—FP7-HEALTH-2013-INNOVATION—602300+1 种基金the Progetti di Rilevante Interesse Nazionale(PRIN)grant 2015F3JHMB to A.T.A.M.A.U.were recipients of Marie Curie fellowships from the European Union funded project RUBICON—H2020-MSCA-RISE-2015_690850 to A.T.
文摘Autosomal dominant osteopetrosis type 2 (ADO2) is a high-density brittle bone disease characterized by bone pain,multiple fractures and skeletal-related events,including nerve compression syndrome and hematological failure.We demonstrated that in mice carrying the heterozygous Clcn7^G213R mutation,whose human mutant homolog CLCN7^G215R affects patients,the clinical impacts of ADO2 extend beyond the skeleton,affecting several other organs.The hallmark of the extra-skeletal alterations is a consistent perivascular fibrosis,associated with high numbers of macrophages and lymphoid infiltrates.Fragmented clinical information in a small cohort of patients confirms extra-skeletal alterations consistent with a systemic disease,in line with the observation that the CLCN7 gene is expressed in many organs.ADO2 mice also show anxiety and depression and their brains exhibit not only perivascular fibrosis but also β-amyloid accumulation and astrogliosis,suggesting the involvement of the nervous system in the pathogenesis of the ADO2 extra-skeletal alterations.Extra-skeletal organs share a similar cellular pathology,confirmed also in vitro in bone marrow mononuclear cells and osteoclasts,characterized by an impairment of the exit pathway of the Clcn7 protein product,ClC7,through the Golgi,with consequent reduced ClC7 expression in late endosomes and lysosomes,associated with high vesicular pH and accumulation of autophagosome markers.Finally,an experimental siRNA therapy,previously proven to counteract the bone phenotype,also improves the extra-skeletal alterations.These results could have important clinical implications,supporting the notion that a systematic evaluation of ADO2 patients for extra-skeletal symptoms could help improve their diagnosis,clinical management,and therapeutic options.
文摘Fluctuations in autonomic cardiovascular regulation during exposure to high altitude may increase the risk of heart attack during waking and sleep. This study compared heart rate variability (HVR) and its components during sleep at low altitude and after 30 - 41 hours of acclimatization at high altitude (3480 m) in five mountain marathon runners controlled for diet, drugs, light-dark cycle and jet lag. In comparison to sea level, RR-intervals during sleep at high altitude decreased significantly (P 0.001). The significant increase in sympathetic autonomic cardiovascular modulation at high altitude protects against excessive oxygen deprivation during sleep. Increases in R-R intervals can require longer periods of acclimatization at3480 m to mitigate the effects of altitude/hypoxia on sympathetic tone, thus reducing cardiovascular distress at rest during waking and sleep and probably before during and after athletic performance at altitude.
文摘Despite improvements in surgical techniques and adjuvant chemotherapy, the overall mortality rates in pan- creatic cancer have generally remained relatively un-changed and the 5-year survival rate is actually below 2%. This paper will address the importance of achieving an early diagnosis and identifying markers for prog- nosis and response to therapy such as genes, proteins, microP, NAs or epigenetic modifications. However, there are still major hurdles when translating investigational biomarkers into routine clinical practice. Furthermore, novel ways of secondary screening in high-risk individu- als, such as artificial neural networks and modern imaging, will be discussed. Drug resistance is ubiquitous in pancreatic cancer. Several mechanisms of drug resistance have already been revealed, including human equilibrative nucleoside transporter-1 status, multidrug resistance proteins, aberrant signaling pathways, mi-croRNAs, stromal influence, epithelial-mesenchymal transition-type cells and recently the presence of can- cer stem cells/cancer-initiating cells. These factors must be considered when developing more customized types of intervention （＇personalized medicine＇S. In the future, multifunctional nanoparticles that combine a specific targeting agent, an imaging probe, a cell-penetrating agent, a biocompatible polymer and an anti-cancer drug may become valuable for the management of pa- tients with pancreatic cancer.
文摘AIM:To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA). METHODS:Sixty-nine ulcerative colitis patients (39 F,30 M) dependent upon/refractory to steroids were treated with GMA. Steroid dependency,clinical activity index (CAI),C reactive protein (CRP) level,erythrocyte sedimentation rate (ESR),values at baseline,use of immunosuppressant,duration of disease,and age and extent of disease were considered for statistical analysis as predictive factors of clinical response. Univariate and multivariate logistic regression models were used. RESULTS:In the univariate analysis,CAI (P = 0.039) and ESR (P = 0.017) levels at baseline were singled out as predictive of clinical remission. In the multivariate analysis steroid dependency [Odds ratio (OR) = 0.390,95% Confidence interval (CI):0.176-0.865,Wald 5.361,P = 0.0160] and low CAI levels at baseline (4 < CAI <7) (OR = 0.770,95% CI:0.425-1.394,Wald 3.747,P = 0.028) proved to be effective as factors predicting clinical response. CONCLUSION:GMA may be a valid therapeutic option for steroid-dependent ulcerative colitis patients with mild-moderate disease and its clinical efficacy seems to persist for 12 mo.
文摘Background:Mastitis caused by different pathogens including Streptococcus uberis(S.uberis)is responsible for huge economic losses to the dairy industry.In order to investigate the potential genetic and epigenetic regulatory mecha‑nisms of subclinical mastitis due to S.uberis,the DNA methylome(whole genome DNA methylation sequencing)and transcriptome(RNA sequencing)of milk somatic cells from cows with naturally occurring S.uberis subclinical mastitis and healthy control cows(n=3/group)were studied.Results:Globally,the DNA methylation levels of CpG sites were low in the promoters and first exons but high in inner exons and introns.The DNA methylation levels at the promoter,first exon and first intron regions were nega‑tively correlated with the expression level of genes at a whole‑genome‑wide scale.In general,DNA methylation level was lower in S.uberis‑positive group(SUG)than in the control group(CTG).A total of 174,342 differentially methylated cytosines(DMCs)(FDR<0.05)were identified between SUG and CTG,including 132,237,7412 and 34,693 DMCs in the context of CpG,CHG and CHH(H=A or T or C),respectively.Besides,101,612 methylation haplotype blocks(MHBs)were identified,including 451 MHBs that were significantly different(dMHB)between the two groups.A total of 2130 differentially expressed(DE)genes(1378 with up‑regulated and 752 with down‑regulated expression)were found in SUG.Integration of methylome and transcriptome data with MethGET program revealed 1623 genes with signifi‑cant changes in their methylation levels and/or gene expression changes(MetGDE genes,MethGET P‑value<0.001).Functional enrichment of genes harboring≥15 DMCs,DE genes and MetGDE genes suggest significant involvement of DNA methylation changes in the regulation of the host immune response to S.uberis infection,especially cytokine activities.Furthermore,discriminant correlation analysis with DIABLO method identified 26 candidate biomarkers,including 6 DE genes,15 CpG‑DMCs and 5 dMHBs that discriminated between SUG and CTG.Conclusion:The integration of methylome and transcriptome of milk somatic cells suggests the possible involve‑ment of DNA methylation changes in the regulation of the host immune response to subclinical mastitis due to S.uberis.The presented genetic and epigenetic biomarkers could contribute to the design of management strategies of subclinical mastitis and breeding for mastitis resistance.
文摘We investigated whether DNA fragmentation in two cytometric sperm populations （PIddimmer and PIbriehter） with different biological characteristics and clinical relevance is related to clinical and color-Doppler ultrasound （CDUS） parameters of the male genital tract. One hundred and sixty males of infertile couples without genetic abnormalities were evaluated for clinical, scrotal, and transrectal CDUS characteristics, presence of prostatitis-like symptoms （with the National Institutes of Health-Chronic Prostatitis Symptom Index） and sperm DNA fragmentation （sDF） in PIdimmer and PIbrighter populations （using TUNEIJPI method coupled with flow cytometry）. Data were adjusted for age （Model 1） along with waistline, testosterone levels, smoking habit, and sexual abstinence （Model 2）. According to the statistical Model 2, PIdi sDF was associated with testicular abnormalities, including lower clinical and ultrasound volume （r = -0.21 and r = -0.20, respectively; P 〈 0.05）, higher FSH levels （r = 0.34, P 〈 0.0001） and occurrence of testicular inhomogeneity （P 〈 0.05） and hypoechogenicity （P 〈 0.05）. PIbrighter sDF was associated with prostate-related symptoms and abnormal signs, including higher NIH-CPSI total and subdomain scores, a higher prevalence of prostatitis-like symptoms and of CDUS alterations such as macro-calcifications, severe echo-texture inhomogeneity, hyperemia （all P 〈 0.05）, and higher arterial peak systolic velocity （r = 0.25, P 〈 0.05）. Our results suggest that DNA fragmentation in PIdimmer sperm, which is related to poor semen quality, mainly originates in the testicles, likely due to apoptosis. Conversely, DNA fragmentation in PIbrighter sperm appears to mainly originate during or after transit through the prostate, increasing with the presence of an inflammatory status of the organ. These results could lead to new perspectives for the identification of therapeutic targets to reduce sDF.
文摘Orthostatic hypertension(OHT)is a condition characterized by an increase in blood pressure after assuming the standing position.[1]Nowadays no consensus definition exists,thus OHT prevalence varies among studies(4%-20.3%).
基金supported by the institutional funding committee of Najran University,Najran,Saudi Arabia(Project code:NU/IFC/ENT/01/007).
文摘Objective:To determine the genetic diversity,natural selection and mutations in Plasmodium(P.)knowlesi drug resistant molecular markers Kelch 13 and dhps gene in clinical samples of Malaysia.Methods:P.knowlesi full-length gene sequences Kelch 13 gene(PkK13)from 40 samples and dhps gene from 30 samples originating from Malaysian Borneo were retrieved from public databases.Genetic diversity,natural selection,and phylogenetic analysis of gene sequences were analysed using DNAsp v5.10 and MEGA v5.2.Results:Seventy-two single nucleotide polymorphic sites(SNPs)across the full-length PkK13 gene(63 synonymous substitutions and 9 non-synonymous substitutions)with nucleotide diversity ofπ~0.005 was observed.Analysis of the full-length Pkdhps gene revealed 73 SNPs andπ~0.006(44 synonymous substitutions and 29 non-synonymous substitutions).A high number of haplotypes(PkK13;H=37 and Pkdhps;H=29)with haplotype diversity of Hd~0.99 were found in both genes,indicating population expansion.Nine mutant alleles were identified in PkK13 amino acid alignment of which,7(Asp3Glu,Lys50Gln,Lys53Glu,Ser123Thr,Ser127Pro,Ser149Thr and Ala169Thr)were within the Plasmodium specific domain,2(Val372Ile and Lys424Asn)were in the BTB/POZ domain and no mutation was observed within the kelch propeller domain.The 29 non-synonymous mutations in the Pkdhps gene were novel and only presented in exon 1 and 2.Conclusions:Monitoring the mutations from clinical samples collected from all states of Malaysia along with clinical efficacy studies will be necessary to determine the drug resistance in P.knowlesi.
文摘BACKGROUND Antinuclear antibodies(ANAs)are crucial in diagnosing autoimmune diseases,mainly systemic lupus erythematosus(SLE).This study aimed to compare the performance of chemiluminescence assay(CLIA)and line immunoassay(LIA)in detecting ANAs in patients with autoimmune diseases,evaluate their diagnostic accuracy for SLE,and develop a novel diagnostic model using CLIA-detected antibodies for SLE.Specimens from patients with autoimmune diseases and physical examination specimens were collected to parallel detect specific antibodies.Individual antibodies'diagnostic performance and a model combining multiple antibodies were assessed.The findings provide valuable insights into improving the diagnosis of SLE through innovative approaches.AIM To compare the performance of CLIA and LIA in detecting ANAs in patients with autoimmune diseases,assess their accuracy for SLE,and develop a novel diagnostic model using CLIA-detected antibodies for SLE.METHODS Specimens have been obtained from 270 patients with clinically diagnosed autoimmune disorders,as well as 130 physical examination specimens.After that,parallel detection of anti-double-stranded DNA(dsDNA)antibody,anti-histone(Histone)antibody,anti-nucleosome(Nuc)antibody,anti-Smith(Sm)antibody,anti-ribosomal P protein(Rib-P)antibody,anti-sicca syndrome A(Ro60)antibody,anti-sicca syndrome A(Ro52)antibody,anti-sicca syndrome(SSB)antibody,anticentromere protein B(Cenp-B)antibody,anti-DNA topoisomerase 1(Scl-70)antibody,anti-histidyl tRNA synthetase(Jo-1)antibody,and anti-mitochondrial M2(AMA-M2)antibody was performed using CLIA and LIA.The detection rates,compliance rates,and diagnostic performance for SLE were compared between the two methodologies,followed by developing a novel diagnostic model for SLE.RESULTS CLIA and LIA exhibited essentially comparable detection rates for anti-dsDNA antibody,anti-Histone antibody,anti-Nuc antibody,anti-Sm antibody,anti-Rib-P antibody,anti-Ro60 antibody,anti-Ro52 antibody,anti-SSB antibody,anti-Cenp-B antibody,anti-DNAScl-70 antibody,anti-Jo-1 antibody and anti-AMA-M2 antibody(P>0.05).The two methods displayed identical results for the detection of anti-dsDNA antibody,anti-Histone antibody,anti-Nuc antibody,anti-Sm antibody,anti-Ro60 antibody,anti-Ro52 antibody,anti-SSB antibody,anti-Cenp-B antibody,anti-Scl-70 antibody,and anti-AMA-M2 antibody(Kappa>0.7,P<0.05),but showed a moderate agreement for the detection of anti-Rib-P antibody and anti-Jo-1 antibody(Kappa=0.671 and 0.665;P<0.05).In addition,the diagnostic performance of these antibodies detected by both methods was similar for SLE.The diagnostic model's area under the curve values,sensitivity,and specificity,including an anti-dsDNA antibody and an anti-Ro60 antibody detected by CLIA,were 0.997,0.962,and 0.978,respectively.These values were higher than the diagnostic performance of individual antibodies.CONCLUSION CLIA and LIA demonstrated excellent overall consistency in detecting ANA profiles.A diagnostic model based on CLIA-detected antibodies can successfully contribute to developing a novel technique for detecting SLE.
文摘Prostate cancer risk stratification relies on several clinical factors. Low-risk patients, characterized by T1–T2a stage, Gleason score (GS) ≤6, and prostate-specific antigen (PSA) <10 ng ml−1, exhibit an excellent prognosis and are suitable for active surveillance (AS). Regular monitoring is essential for these patients, including PSA tests every 3–6 months, annual digital rectal exams (DRE), and prostate biopsies every 6–12 months, followed by less frequent biopsies every 2–5 years. Epstein criteria, which consider GS ≤6, PSA density (PSAD) <0.15 ng ml−2, limited tumor involvement in cores, and absence of high-risk features, help predict pathologic and biochemical relapse-free survival and guide AS management.
