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
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
BACKGROUND Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis(AP)but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surround...BACKGROUND Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis(AP)but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic metabolism.This non-pancreatic hyperlipasemia(NPHL)is puzzling for attending physicians during the diagnostic procedure for AP.It would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it.A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently lacking.AIM To perform a detailed clinical and laboratory characterization of NPHL in a large prospective patient cohort with an assessment of parameters determining disease outcomes.METHODS A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal(ULN)was prospectively evaluated over 31 months.Patients were identified using daily electronic laboratory reports developed to support an ongoing observational,multicenter,prospective cohort study called the EASY trial(ISRCTN10525246)to establish a simple,easy,and accurate clinical scoring system for early prognostication of AP.Diagnosis of NPHL was established based on≥3×ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of pancreatitis.RESULTS A total of 808 patients[male,n=420(52%);median age(IQR):65(51-75)years]were diagnosed with≥3×ULN serum lipase levels.A total of 392 patients had AP,whereas 401 had NPHL with more than 20 different etiologies.Sepsis and acute kidney injury(AKI)were the most prevalent etiologies of NPHL(27.7%and 33.2%,respectively).The best discriminative cut-off value for lipase was≥666 U/L(sensitivity,71.4%;specificity,88.8%).The presence of AKI or sepsis negatively affected the diagnostic performance of lipase.NPHL was associated with a higher in-hospital mortality than AP(22.4%vs 5.1%,P<0.001).In multivariate binary logistic regression,not lipase but increased amylase level(>244 U/L)and neutrophil-to-lymphocyte ratio(NLR)(>10.37,OR:3.71,95%CI:2.006-6.863,P<0.001),decreased albumin level,age,and presence of sepsis were independent risk factors for in-hospital mortality in NPHL.CONCLUSION NPHL is a common cause of lipase elevation and is associated with high mortality rates.Increased NLR value was associated with the highest mortality risk.The presence of sepsis/AKI significantly deteriorates the serological differentiation of AP from NPHL.展开更多
Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression an...Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression and diminished chemotherapy efficacy,impacting patient outcomes through various mechanisms such as oxidative stress,activation of metabolic pathways,and altered protein modifications that hinder apoptosis and enhance tumor survival.Clinical evidence shows that T2DM patients experience higher rates of chemoresistance and reduced disease-free survival and overall survival compared to non-diabetic patients.Specifically,those with poor glycemic control exhibit increased chemo-resistance and poorer survival metrics.Antidiabetic treatments,including metformin,acarbose,and gliclazide,show promise in improving chemotherapy response and glycemic management,potentially enhancing patient outcomes.Addressing this challenge requires a comprehensive,multidisciplinary approach involving oncologists,endocrino-logists,and surgeons to optimize patient care.Integrated strategies that prioritize glycemic control are essential for reducing chemoresistance and improving survival in CRC patients with T2DM.展开更多
Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was cond...Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.展开更多
Background: The prevalence of benign prostatic hyperplasia, BPH is increasing in our environment. Besides androgens and age could there be other risk factors? Aim: To investigate the roles of sexually transmitted infe...Background: The prevalence of benign prostatic hyperplasia, BPH is increasing in our environment. Besides androgens and age could there be other risk factors? Aim: To investigate the roles of sexually transmitted infections, STI and frequency of ejaculation as risk factors for BPH. Methods: It was a prospective observational study carried out among predominantly Christian communities near Port Harcourt, a major cosmopolitan city in the oil rich Rivers State, in the Niger Delta region of Nigeria. Adult males above the age of 40 yrs old with no history of prostate cancer were invited to participate. History of marriage, duration of marriage, number of wives/sexual partners, frequency of sex or ejaculation and present or past history of STI were obtained through an interpreter administered questionnaire. Diagnosis of BPH was based on presence of lower urinary tract symptoms, ultrasound determination of increased prostate size and histopathology report to rule out prostate cancer. Linear logistic regression and odds ration were used to establish strength of association between BPH and frequency of ejaculation and history of various causative organisms for STI. Statistical significance was determined at p value of Results: 754 respondents participated. Age ranged from 40 to 81 years. 92.6% were in a single relationship. 58.4% had 1 - 5 ejaculations per week. 8.2% has had syphilis, 32.6% has had gonorrhea and 1.1% has had candida infection. There was an observed positive relationship between history of gonorrhoea and increase in prostate size but the association was not statistically significant;syphilis showed no positive relationship with prostate enlargement;incidence of candidiasis was too low to establish causal relationship. Individuals who had sex once a week or less showed a higher prevalence of moderate/severe enlargement (42.3%) compared to those with more frequent sexual activity (35.7%) a relationship that approached significance (p = 0.071), with an odds ratio of 1.3 and narrow CI (0.9 to 1.7), suggesting a potential association that requires further investigation. Conclusion: There is an observed causal relationship between both previous history of gonorrhea infection and reduced frequency of ejaculation and prostate enlargement but these associations do not attain statistical significance and would need further studies.展开更多
Portal hypertension(PH)is a major complication of chronic liver disease,often leading to serious clinical consequences such as variceal bleeding,ascites,and splenomegaly.The current gold standard for PH diagnosis,name...Portal hypertension(PH)is a major complication of chronic liver disease,often leading to serious clinical consequences such as variceal bleeding,ascites,and splenomegaly.The current gold standard for PH diagnosis,namely,hepatic venous pressure gradient measurement,is invasive and not widely available.Transient elastography has emerged as a non-invasive alternative for assessing liver stiffness(LS),and recent studies have highlighted the potential role of splenic stiffness(SS)in evaluating PH severity.This narrative review summarizes the available evidence on the utility of splenic transient elastography in assessing PH.We evaluated its diagnostic accuracy,technical challenges,and clinical applications,particularly in distinguishing between cirrhotic PH(CPH)and noncirrhotic PH(NCPH).A comprehensive literature search was conducted using the PubMed database,focusing on studies that assess splenic elastography in the diagnosis and prognosis of PH.This review compares splenic elastography with other non-invasive imaging modalities,including MR elastography and shearwave elastography.Additionally,we examined the role of SS using elastography in predicting the presence of esophageal varices and its potential impact on reducing the need for endoscopic screening.Studies have demonstrated that splenic elastography correlates well with PH severity,with cut-off values ranging between 45 kPa and 50 kPa for significant PH detection.Splenic elastography,when combined with platelet count and LS measurements,improves diagnostic accuracy and risk stratification for the occurrence of variceal bleeding.Despite its clinical promise,technical challenges such as patient positioning,body habitus,and probe selection remain key limitations.Notably,splenic elastography may be particularly useful in diagnosing NCPH,where LS remains normal but PH is present.Splenic transient elastography is a valuable adjunct in the non-invasive assessment of PH.Its ability to predict varices,differentiate between CPH and NCPH,and reduce unnecessary endoscopies suggests that it should be incorporated into routine hepatology practice.Future research should focus on refining SS cut-offs,evaluating its cost-effectiveness,and integrating splenic elastography into clinical guidelines for PH management.展开更多
Antibody-mediated rejection(ABMR)and recurrent primary renal disease(PRD)represent major causes of kidney transplant(KT)loss.The standard of care for desensitization,ABMR,and relapsing autoimmune glomerulopathies or n...Antibody-mediated rejection(ABMR)and recurrent primary renal disease(PRD)represent major causes of kidney transplant(KT)loss.The standard of care for desensitization,ABMR,and relapsing autoimmune glomerulopathies or nephrotic syndrome includes apheresis for antibody removal and polyclonal immunoglobulin for antibody blockage.Although frequently used to achieve B-cell depletion,the administration of the type 1 anti-CD20 monoclonal antibodies(mAb)rituximab(RTX)or ofatumumab(OFA)has failed to demonstrate a significant survival benefit.Obinutuzumab(OBI)is a humanized glycoengineered type 2 anti-CD20 mAb.Compared to RTX or OFA,OBI-induced B-cell depletion is not related to complement-dependent cytotoxicity,mostly operating through antibody-dependent cell-mediated cytotoxicity,antibody-dependent phagocytosis,and direct cell death.These characteristics could play a pivotal role in the development of new anti-rejection strategies,enabling the simultaneous administration of complement inhibitors and B-cell-depleting agents.OBI has also demonstrated more powerful peripheral and central B-cell depletion capacities than RTX,with enhanced effects on memory B cells and plasmablasts.In patients with autoimmune glomerulopathies or multidrug-dependent nephrotic syndrome,OBI has shown encouraging results,representing a potential evolution of the treatment of post-transplant relapsing PRD.The present review summarizes the current knowledge on OBI use in KT setting.展开更多
Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair,offering new perspectives on reproductive health.This manuscript highlights the study by Zhang et al,w...Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair,offering new perspectives on reproductive health.This manuscript highlights the study by Zhang et al,which investigates the effects of miR-214-5p and miR-21-5p in hypoxic cell-derived exosomes on human umbilical cord mesenchymal stem cells.The study reveals that low levels of these microRNAs activate the signal transducer and activator of transcription 3 signaling pathway,enhancing human umbilical cord mesenchymal stem cell migration and differentiation.These findings provide novel insights into therapeutic strategies for improving endometrial health and addressing infertility linked to thin endometrium.展开更多
Artemisia dracunculus L.,or tarragon,is a perennial herb from the Asteraceae family that is extensively cultivated for its aromatic leaves,which are valued for its preventative and therapeutic properties in both cooke...Artemisia dracunculus L.,or tarragon,is a perennial herb from the Asteraceae family that is extensively cultivated for its aromatic leaves,which are valued for its preventative and therapeutic properties in both cookery and traditional medicine.This study aims to investigate the antibacterial,antioxidant,and anti-inflammatory properties of A.dracunculus(tarragon)essential oil(ADEO),with estragole(57.23%)identified as the major compound through gas chromatography-mass spectrometry(GC-MS)analysis.ADEO exhibited varying degrees of antibacterial activity,with Escherichia coli showing higher resistance inhibition zone(IZ)=14.7±0.58 mm,minimum (inhibitory concentration(MIC)=2%and minimum bactericidal concentration(MBC)=4%),while Bacillus subtilis(IZ=24.05±2.11 mm and MIC=MBC=0.125%)and Staphylococcus aureus(IZ=18.69±1.45 mm,MIC=0.0612%and MBC=0.125%)were more sensitive to its actions.Antioxidant ability was assessed using 1,1-diphenyl-2-picrylhydrazil(DPPH),2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),xanthine oxidase inhibition,and beta-carotene bleaching assays.ADEO showed remarkable antiradical effect on DPPH(IC_(50)=127.05±3.47μg/mL)and ABTS radical(IC_(50)=89.60±8.73μg/mL)as well as significant inhibition of xanthine oxidase(IC_(50)=47.9±2.04μg/mL)and lipid peroxidation(IC_(50)=231.63±5.21μg/mL).ADEO also showed significant anti-inflammatory activity by inhibiting the enzymesCOX-1(IC_(50)=59.2±2.43μg/mL),Cyclo-oxygenase-2(COX-2)(IC_(50)=74.68±1.34μg/mL)and 5-lipooxygense(5-LOX)(IC_(50)=93.18±1.87μg/mL),which are involved in the inflammatory pathway.These findings suggest that ADEO,with its high estragole content,holds promising potential as a natural antibacterial,antioxidant,and anti-inflammatory agent for preventive and therapeutic applications.Further research is needed to explore its safety and efficacy in clinical settings.展开更多
Background: The maternal and neonatal morbidity caused by prolonged labour, maternal exhaustion and other factors push clinicians to speed up the delivery process by employing equipment such as vacuum suction or force...Background: The maternal and neonatal morbidity caused by prolonged labour, maternal exhaustion and other factors push clinicians to speed up the delivery process by employing equipment such as vacuum suction or forceps to save the newborn. The purpose of this study was to determine the prevalence of vacuum-assisted vaginal delivery (VAVD) and its associated short-term maternal and neonatal outcomes at Ndola Teaching Hospital. Methods: A retrospective cross-sectional descriptive study through the analysis of routine data for women with singleton-term pregnancies who delivered by vacuum compared with spontaneous vaginal delivery was done at a tertiary hospital for the years 2020 and 2021. Chi-square and Logistic regression were used to investigate factors of vacuum delivery and to adjust for potential confounders. Results: Results showed that VAVD was mostly performed in women who had delayed second stage of labour (25.4%), maternal exhaustion (16.0%), foetal distress in the second stage of labour (12.3%). The overall VAVD prevalence was 3.7% (581/15591). Logistic regression showed that multiparous women were noted to be 87.5% (aOR 0.125;95% CI 0.025 - 0.629;p = 0.012) less likely to undergo VAVD compared to nulliparous women. Registrars were almost 6 times (aOR 5.650;95% CI 1.458 - 22.222, p = 0.012) more likely to conduct VAVD compared to midwives. Episiotomy was 3 times (aOR 3.390;95% CI 1.185 - 9.524;p Conclusion: The findings indicate the underutilisation of VAVD at NTH based on the low prevalence of 3.7%. VAVD outcomes were affected by multiparity, skill level and Episiotomy procedure, in addition, VAVD influenced admission to the NICU. Hence, there is a need to increase skills in VAVD among first-line healthcare workers such as midwives and intern doctors.展开更多
Hepatitis B virus infection remains a significant global health challenge,particularly in endemic regions like Vietnam.This article examines the groundbreaking study by Nguyen et al,which investigates the relationship...Hepatitis B virus infection remains a significant global health challenge,particularly in endemic regions like Vietnam.This article examines the groundbreaking study by Nguyen et al,which investigates the relationship between human leukocyte antigen-DP/DQ polymorphisms and hepatitis B virus-related liver disease progression.Through advanced multi-clustering analysis,the study reveals that the A-A-A haplotype(rs2856718-rs3077-rs9277535)provides protection against disease progression,while the G-G-G haplotype correlates with increased hepatocellular carcinoma susceptibility.The integration of machine learning approaches with genetic data offers promising avenues for refined disease prediction and personalized therapeutic strategies.This article discusses the implications for expanding study populations,implementing longitudinal cohort studies,and leveraging artificial intelligence for improved patient outcomes.展开更多
Pediatric emergency care(PEC)encompasses the specialized medical care delivered to infants,children,and adolescents facing urgent medical situations,addressing critical conditions such as infections,allergic responses...Pediatric emergency care(PEC)encompasses the specialized medical care delivered to infants,children,and adolescents facing urgent medical situations,addressing critical conditions such as infections,allergic responses,seizures,respiratory distress,and trauma.PEC calls for prompt,focused interventions to address each child's developmental and physiological needs.The literature was searched using Google Scholar,PubMed,and the Cochrane Library to retrieve studies assessing quality indicators and outcomes in pediatric emergencies.The search was limited to papers published in peer-reviewed journals between 01 Jan 2000 and 15 Dec 2024.This review evaluates current PEC standards such as patient safety,diagnostic precision,timeliness,and patient and family satisfaction.Patient safety is vital because children are particularly vulnerable to medical errors,such as inappropriate doses of medication.The provision of high-quality PEC is hampered by systemic issues such as inadequate training,a lack of re-sources,and restricted access to treatment.Telemedicine,pediatric transport units,artificial intelligence applications for diagnostics,and simulation-based training are suggested approaches to overcome these challenges.Research net-works and quality improvement initiatives are important steps to improve PEC care.展开更多
Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment ...Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment style may have a role in shaping such associations.Aims This study aims to provide a unified model of the impact of ACEs on NSSI,exploring complex post-traumatic stress disorder(cPTSD)symptoms and dissociation as potential mediators and the role of the predominant attachment style in affecting such associations.Methods 1010 young individuals attending the last year of high school participated in this cross-sectional study.ACEs,cPTSD,dissociation and NSSI were evaluated using self-report questionnaires.We fitted a path model of NSSI,with ACEs as exogenous variables and cPTSD and dissociation as sequential mediators.Secure,fearful and preoccupied attachment styles were modelled as grouping variables.Results Our findings showed that dissociation mediated the impact of ACEs on NSSI in subjects with a fearful attachment style,as opposed to those with a preoccupied attachment for whom cPTSD symptoms mediated the ACEs-NSSI association.Conclusions Attachment styles moderate the relationship between ACEs and NSSI,with either dissociation or post-traumatic symptomatology mediating the impact of ACEs on NSSI,depending on the predominant attachment style.Our results highlight the importance of attachment as a pathway modifier in the relationships between different psychopathology dimensions,providing a useful framework to better conceptualise the ACEs-NSSI association.展开更多
Background:The JAK2^(V617F)mutation plays a crucial part in the pathogenesis of myeloproliferative neoplasms(MPN),which includes polycythemia vera(PV),essential thrombocythemia(ET),and primary myelofibrosis(PMF)leadin...Background:The JAK2^(V617F)mutation plays a crucial part in the pathogenesis of myeloproliferative neoplasms(MPN),which includes polycythemia vera(PV),essential thrombocythemia(ET),and primary myelofibrosis(PMF)leading to aberrant proliferation and survival of hematopoietic cells.Alongside the challenges of drug resistance and side effects,identifying novel compounds that selectively target JAK2^(V617F)could provide more effective and safer therapeutic options for patients with MPNs.Materials and Methods:We employed computational approaches like high-throughput virtual screening,molecular dynamics simulations(MDS),and binding free energy calculations to identify inhibitors targeting wild and mutant JAK2 kinases.JAK2^(V617F)positive HEL,wild type JAK2 positive TF-1,and non-cancerous Vero cells were used for in vitro validations.Results:SBLJ23 emerged as a top candidate inhibitor with specificity for JAK2^(V617F).Protein-ligand interaction studies and MDS revealed stable interactions and binding of SBLJ23 over the simulation period,with Root Mean Square Deviation(RMSD)indicating consistent binding after 1t15ns.SBLJ23 displayed a half maximal inhibitory concentration(IC_(50))value of 522.4 nM against the JAK2 enzyme.The compound exhibited inhibition of cell proliferation in HEL and TF-1 cells,with half maximal cell growth inhibitory concentration(GI 50)values of 2.51 and 15.87μM,respectively.Moreover,SBLJ23 induced G 2/M cell cycle arrest in HEL cells to facilitate apoptosis in these cell lines.The compound significantly reduced the percentage of phospho JAK2 and phospho STAT3 in HEL cells.Conclusion:High binding affinity,stable interaction profile,favorable binding free energy,and in vitro validations claim SBLJ23 as a potential lead compound against JAK2^(V617F)and suggest further development and optimization towards clinical application in managing myeloproliferative neoplasms.展开更多
BACKGROUND Endoscopic therapy is the primary approach for treating Mallory-Weiss syndro-me,particularly under conditions of mucosal protection and gastric acid suppre-ssion.However,for a subset of patients who cannot ...BACKGROUND Endoscopic therapy is the primary approach for treating Mallory-Weiss syndro-me,particularly under conditions of mucosal protection and gastric acid suppre-ssion.However,for a subset of patients who cannot undergo endoscopic interven-tion or for whom such treatment proves ineffective,alternative measures like arterial embolization or surgical intervention may be required.While hyperbaric oxygen therapy(HBOT)has been applied across a range of medical conditions,its application in managing hemorrhage due to gastric tears remains undocumented.CASE SUMMARY A 52-year-old patient was admitted with symptoms of hematemesis and melena,and an endoscopy revealed a gastric fundus tear approximately 4 cm×5 cm in size.The lesion was considered unsuitable for endoscopic repair by the attending endoscopist.Despite conservative measures,including fasting and acid sup-pression,the patient experienced persistent bleeding and a substantial decrease in hemoglobin levels relative to admission values.Following a multidisciplinary consultation,HBOT was initiated,resulting in the cessation of bleeding and rapid wound healing.CONCLUSION For patients with gastric tears presenting with active hemorrhage,HBOT might offer an effective alternative when conventional endoscopic therapies are not viable or have been unsuccessful.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.
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.
基金Supported by the Economic Development and Innovation Operative Program Grant,No.GINOP 2.3.2-15-2016-00048“StayAlive”Human Resources Development Operational Program Grant of the National Research Development and Innovation Office,No.EFOP-3.6.2-16-2017-00006.
文摘BACKGROUND Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis(AP)but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic metabolism.This non-pancreatic hyperlipasemia(NPHL)is puzzling for attending physicians during the diagnostic procedure for AP.It would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it.A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently lacking.AIM To perform a detailed clinical and laboratory characterization of NPHL in a large prospective patient cohort with an assessment of parameters determining disease outcomes.METHODS A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal(ULN)was prospectively evaluated over 31 months.Patients were identified using daily electronic laboratory reports developed to support an ongoing observational,multicenter,prospective cohort study called the EASY trial(ISRCTN10525246)to establish a simple,easy,and accurate clinical scoring system for early prognostication of AP.Diagnosis of NPHL was established based on≥3×ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of pancreatitis.RESULTS A total of 808 patients[male,n=420(52%);median age(IQR):65(51-75)years]were diagnosed with≥3×ULN serum lipase levels.A total of 392 patients had AP,whereas 401 had NPHL with more than 20 different etiologies.Sepsis and acute kidney injury(AKI)were the most prevalent etiologies of NPHL(27.7%and 33.2%,respectively).The best discriminative cut-off value for lipase was≥666 U/L(sensitivity,71.4%;specificity,88.8%).The presence of AKI or sepsis negatively affected the diagnostic performance of lipase.NPHL was associated with a higher in-hospital mortality than AP(22.4%vs 5.1%,P<0.001).In multivariate binary logistic regression,not lipase but increased amylase level(>244 U/L)and neutrophil-to-lymphocyte ratio(NLR)(>10.37,OR:3.71,95%CI:2.006-6.863,P<0.001),decreased albumin level,age,and presence of sepsis were independent risk factors for in-hospital mortality in NPHL.CONCLUSION NPHL is a common cause of lipase elevation and is associated with high mortality rates.Increased NLR value was associated with the highest mortality risk.The presence of sepsis/AKI significantly deteriorates the serological differentiation of AP from NPHL.
文摘Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression and diminished chemotherapy efficacy,impacting patient outcomes through various mechanisms such as oxidative stress,activation of metabolic pathways,and altered protein modifications that hinder apoptosis and enhance tumor survival.Clinical evidence shows that T2DM patients experience higher rates of chemoresistance and reduced disease-free survival and overall survival compared to non-diabetic patients.Specifically,those with poor glycemic control exhibit increased chemo-resistance and poorer survival metrics.Antidiabetic treatments,including metformin,acarbose,and gliclazide,show promise in improving chemotherapy response and glycemic management,potentially enhancing patient outcomes.Addressing this challenge requires a comprehensive,multidisciplinary approach involving oncologists,endocrino-logists,and surgeons to optimize patient care.Integrated strategies that prioritize glycemic control are essential for reducing chemoresistance and improving survival in CRC patients with T2DM.
文摘Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.
文摘Background: The prevalence of benign prostatic hyperplasia, BPH is increasing in our environment. Besides androgens and age could there be other risk factors? Aim: To investigate the roles of sexually transmitted infections, STI and frequency of ejaculation as risk factors for BPH. Methods: It was a prospective observational study carried out among predominantly Christian communities near Port Harcourt, a major cosmopolitan city in the oil rich Rivers State, in the Niger Delta region of Nigeria. Adult males above the age of 40 yrs old with no history of prostate cancer were invited to participate. History of marriage, duration of marriage, number of wives/sexual partners, frequency of sex or ejaculation and present or past history of STI were obtained through an interpreter administered questionnaire. Diagnosis of BPH was based on presence of lower urinary tract symptoms, ultrasound determination of increased prostate size and histopathology report to rule out prostate cancer. Linear logistic regression and odds ration were used to establish strength of association between BPH and frequency of ejaculation and history of various causative organisms for STI. Statistical significance was determined at p value of Results: 754 respondents participated. Age ranged from 40 to 81 years. 92.6% were in a single relationship. 58.4% had 1 - 5 ejaculations per week. 8.2% has had syphilis, 32.6% has had gonorrhea and 1.1% has had candida infection. There was an observed positive relationship between history of gonorrhoea and increase in prostate size but the association was not statistically significant;syphilis showed no positive relationship with prostate enlargement;incidence of candidiasis was too low to establish causal relationship. Individuals who had sex once a week or less showed a higher prevalence of moderate/severe enlargement (42.3%) compared to those with more frequent sexual activity (35.7%) a relationship that approached significance (p = 0.071), with an odds ratio of 1.3 and narrow CI (0.9 to 1.7), suggesting a potential association that requires further investigation. Conclusion: There is an observed causal relationship between both previous history of gonorrhea infection and reduced frequency of ejaculation and prostate enlargement but these associations do not attain statistical significance and would need further studies.
文摘Portal hypertension(PH)is a major complication of chronic liver disease,often leading to serious clinical consequences such as variceal bleeding,ascites,and splenomegaly.The current gold standard for PH diagnosis,namely,hepatic venous pressure gradient measurement,is invasive and not widely available.Transient elastography has emerged as a non-invasive alternative for assessing liver stiffness(LS),and recent studies have highlighted the potential role of splenic stiffness(SS)in evaluating PH severity.This narrative review summarizes the available evidence on the utility of splenic transient elastography in assessing PH.We evaluated its diagnostic accuracy,technical challenges,and clinical applications,particularly in distinguishing between cirrhotic PH(CPH)and noncirrhotic PH(NCPH).A comprehensive literature search was conducted using the PubMed database,focusing on studies that assess splenic elastography in the diagnosis and prognosis of PH.This review compares splenic elastography with other non-invasive imaging modalities,including MR elastography and shearwave elastography.Additionally,we examined the role of SS using elastography in predicting the presence of esophageal varices and its potential impact on reducing the need for endoscopic screening.Studies have demonstrated that splenic elastography correlates well with PH severity,with cut-off values ranging between 45 kPa and 50 kPa for significant PH detection.Splenic elastography,when combined with platelet count and LS measurements,improves diagnostic accuracy and risk stratification for the occurrence of variceal bleeding.Despite its clinical promise,technical challenges such as patient positioning,body habitus,and probe selection remain key limitations.Notably,splenic elastography may be particularly useful in diagnosing NCPH,where LS remains normal but PH is present.Splenic transient elastography is a valuable adjunct in the non-invasive assessment of PH.Its ability to predict varices,differentiate between CPH and NCPH,and reduce unnecessary endoscopies suggests that it should be incorporated into routine hepatology practice.Future research should focus on refining SS cut-offs,evaluating its cost-effectiveness,and integrating splenic elastography into clinical guidelines for PH management.
文摘Antibody-mediated rejection(ABMR)and recurrent primary renal disease(PRD)represent major causes of kidney transplant(KT)loss.The standard of care for desensitization,ABMR,and relapsing autoimmune glomerulopathies or nephrotic syndrome includes apheresis for antibody removal and polyclonal immunoglobulin for antibody blockage.Although frequently used to achieve B-cell depletion,the administration of the type 1 anti-CD20 monoclonal antibodies(mAb)rituximab(RTX)or ofatumumab(OFA)has failed to demonstrate a significant survival benefit.Obinutuzumab(OBI)is a humanized glycoengineered type 2 anti-CD20 mAb.Compared to RTX or OFA,OBI-induced B-cell depletion is not related to complement-dependent cytotoxicity,mostly operating through antibody-dependent cell-mediated cytotoxicity,antibody-dependent phagocytosis,and direct cell death.These characteristics could play a pivotal role in the development of new anti-rejection strategies,enabling the simultaneous administration of complement inhibitors and B-cell-depleting agents.OBI has also demonstrated more powerful peripheral and central B-cell depletion capacities than RTX,with enhanced effects on memory B cells and plasmablasts.In patients with autoimmune glomerulopathies or multidrug-dependent nephrotic syndrome,OBI has shown encouraging results,representing a potential evolution of the treatment of post-transplant relapsing PRD.The present review summarizes the current knowledge on OBI use in KT setting.
基金the National Natural Science Foundation of China,No.82170406 and No.81970238the Royal Society United Kingdom,No.IEC\NSFC\201094.
文摘Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair,offering new perspectives on reproductive health.This manuscript highlights the study by Zhang et al,which investigates the effects of miR-214-5p and miR-21-5p in hypoxic cell-derived exosomes on human umbilical cord mesenchymal stem cells.The study reveals that low levels of these microRNAs activate the signal transducer and activator of transcription 3 signaling pathway,enhancing human umbilical cord mesenchymal stem cell migration and differentiation.These findings provide novel insights into therapeutic strategies for improving endometrial health and addressing infertility linked to thin endometrium.
文摘Artemisia dracunculus L.,or tarragon,is a perennial herb from the Asteraceae family that is extensively cultivated for its aromatic leaves,which are valued for its preventative and therapeutic properties in both cookery and traditional medicine.This study aims to investigate the antibacterial,antioxidant,and anti-inflammatory properties of A.dracunculus(tarragon)essential oil(ADEO),with estragole(57.23%)identified as the major compound through gas chromatography-mass spectrometry(GC-MS)analysis.ADEO exhibited varying degrees of antibacterial activity,with Escherichia coli showing higher resistance inhibition zone(IZ)=14.7±0.58 mm,minimum (inhibitory concentration(MIC)=2%and minimum bactericidal concentration(MBC)=4%),while Bacillus subtilis(IZ=24.05±2.11 mm and MIC=MBC=0.125%)and Staphylococcus aureus(IZ=18.69±1.45 mm,MIC=0.0612%and MBC=0.125%)were more sensitive to its actions.Antioxidant ability was assessed using 1,1-diphenyl-2-picrylhydrazil(DPPH),2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),xanthine oxidase inhibition,and beta-carotene bleaching assays.ADEO showed remarkable antiradical effect on DPPH(IC_(50)=127.05±3.47μg/mL)and ABTS radical(IC_(50)=89.60±8.73μg/mL)as well as significant inhibition of xanthine oxidase(IC_(50)=47.9±2.04μg/mL)and lipid peroxidation(IC_(50)=231.63±5.21μg/mL).ADEO also showed significant anti-inflammatory activity by inhibiting the enzymesCOX-1(IC_(50)=59.2±2.43μg/mL),Cyclo-oxygenase-2(COX-2)(IC_(50)=74.68±1.34μg/mL)and 5-lipooxygense(5-LOX)(IC_(50)=93.18±1.87μg/mL),which are involved in the inflammatory pathway.These findings suggest that ADEO,with its high estragole content,holds promising potential as a natural antibacterial,antioxidant,and anti-inflammatory agent for preventive and therapeutic applications.Further research is needed to explore its safety and efficacy in clinical settings.
文摘Background: The maternal and neonatal morbidity caused by prolonged labour, maternal exhaustion and other factors push clinicians to speed up the delivery process by employing equipment such as vacuum suction or forceps to save the newborn. The purpose of this study was to determine the prevalence of vacuum-assisted vaginal delivery (VAVD) and its associated short-term maternal and neonatal outcomes at Ndola Teaching Hospital. Methods: A retrospective cross-sectional descriptive study through the analysis of routine data for women with singleton-term pregnancies who delivered by vacuum compared with spontaneous vaginal delivery was done at a tertiary hospital for the years 2020 and 2021. Chi-square and Logistic regression were used to investigate factors of vacuum delivery and to adjust for potential confounders. Results: Results showed that VAVD was mostly performed in women who had delayed second stage of labour (25.4%), maternal exhaustion (16.0%), foetal distress in the second stage of labour (12.3%). The overall VAVD prevalence was 3.7% (581/15591). Logistic regression showed that multiparous women were noted to be 87.5% (aOR 0.125;95% CI 0.025 - 0.629;p = 0.012) less likely to undergo VAVD compared to nulliparous women. Registrars were almost 6 times (aOR 5.650;95% CI 1.458 - 22.222, p = 0.012) more likely to conduct VAVD compared to midwives. Episiotomy was 3 times (aOR 3.390;95% CI 1.185 - 9.524;p Conclusion: The findings indicate the underutilisation of VAVD at NTH based on the low prevalence of 3.7%. VAVD outcomes were affected by multiparity, skill level and Episiotomy procedure, in addition, VAVD influenced admission to the NICU. Hence, there is a need to increase skills in VAVD among first-line healthcare workers such as midwives and intern doctors.
基金Supported by National Natural Science Foundation of China,No.82170406 and No.81970238.
文摘Hepatitis B virus infection remains a significant global health challenge,particularly in endemic regions like Vietnam.This article examines the groundbreaking study by Nguyen et al,which investigates the relationship between human leukocyte antigen-DP/DQ polymorphisms and hepatitis B virus-related liver disease progression.Through advanced multi-clustering analysis,the study reveals that the A-A-A haplotype(rs2856718-rs3077-rs9277535)provides protection against disease progression,while the G-G-G haplotype correlates with increased hepatocellular carcinoma susceptibility.The integration of machine learning approaches with genetic data offers promising avenues for refined disease prediction and personalized therapeutic strategies.This article discusses the implications for expanding study populations,implementing longitudinal cohort studies,and leveraging artificial intelligence for improved patient outcomes.
文摘Pediatric emergency care(PEC)encompasses the specialized medical care delivered to infants,children,and adolescents facing urgent medical situations,addressing critical conditions such as infections,allergic responses,seizures,respiratory distress,and trauma.PEC calls for prompt,focused interventions to address each child's developmental and physiological needs.The literature was searched using Google Scholar,PubMed,and the Cochrane Library to retrieve studies assessing quality indicators and outcomes in pediatric emergencies.The search was limited to papers published in peer-reviewed journals between 01 Jan 2000 and 15 Dec 2024.This review evaluates current PEC standards such as patient safety,diagnostic precision,timeliness,and patient and family satisfaction.Patient safety is vital because children are particularly vulnerable to medical errors,such as inappropriate doses of medication.The provision of high-quality PEC is hampered by systemic issues such as inadequate training,a lack of re-sources,and restricted access to treatment.Telemedicine,pediatric transport units,artificial intelligence applications for diagnostics,and simulation-based training are suggested approaches to overcome these challenges.Research net-works and quality improvement initiatives are important steps to improve PEC care.
基金supported by #NEXTGENERATIONEU(NGEU)and funded by the Ministry of University and Research(MUR),National Recovery and Resilience Plan(NRRP),project MNESYS(PE0000006)-(DN.155311.10.2022)supported by Sapienza Grant 2021(RM12117A60BDF685).
文摘Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment style may have a role in shaping such associations.Aims This study aims to provide a unified model of the impact of ACEs on NSSI,exploring complex post-traumatic stress disorder(cPTSD)symptoms and dissociation as potential mediators and the role of the predominant attachment style in affecting such associations.Methods 1010 young individuals attending the last year of high school participated in this cross-sectional study.ACEs,cPTSD,dissociation and NSSI were evaluated using self-report questionnaires.We fitted a path model of NSSI,with ACEs as exogenous variables and cPTSD and dissociation as sequential mediators.Secure,fearful and preoccupied attachment styles were modelled as grouping variables.Results Our findings showed that dissociation mediated the impact of ACEs on NSSI in subjects with a fearful attachment style,as opposed to those with a preoccupied attachment for whom cPTSD symptoms mediated the ACEs-NSSI association.Conclusions Attachment styles moderate the relationship between ACEs and NSSI,with either dissociation or post-traumatic symptomatology mediating the impact of ACEs on NSSI,depending on the predominant attachment style.Our results highlight the importance of attachment as a pathway modifier in the relationships between different psychopathology dimensions,providing a useful framework to better conceptualise the ACEs-NSSI association.
文摘Background:The JAK2^(V617F)mutation plays a crucial part in the pathogenesis of myeloproliferative neoplasms(MPN),which includes polycythemia vera(PV),essential thrombocythemia(ET),and primary myelofibrosis(PMF)leading to aberrant proliferation and survival of hematopoietic cells.Alongside the challenges of drug resistance and side effects,identifying novel compounds that selectively target JAK2^(V617F)could provide more effective and safer therapeutic options for patients with MPNs.Materials and Methods:We employed computational approaches like high-throughput virtual screening,molecular dynamics simulations(MDS),and binding free energy calculations to identify inhibitors targeting wild and mutant JAK2 kinases.JAK2^(V617F)positive HEL,wild type JAK2 positive TF-1,and non-cancerous Vero cells were used for in vitro validations.Results:SBLJ23 emerged as a top candidate inhibitor with specificity for JAK2^(V617F).Protein-ligand interaction studies and MDS revealed stable interactions and binding of SBLJ23 over the simulation period,with Root Mean Square Deviation(RMSD)indicating consistent binding after 1t15ns.SBLJ23 displayed a half maximal inhibitory concentration(IC_(50))value of 522.4 nM against the JAK2 enzyme.The compound exhibited inhibition of cell proliferation in HEL and TF-1 cells,with half maximal cell growth inhibitory concentration(GI 50)values of 2.51 and 15.87μM,respectively.Moreover,SBLJ23 induced G 2/M cell cycle arrest in HEL cells to facilitate apoptosis in these cell lines.The compound significantly reduced the percentage of phospho JAK2 and phospho STAT3 in HEL cells.Conclusion:High binding affinity,stable interaction profile,favorable binding free energy,and in vitro validations claim SBLJ23 as a potential lead compound against JAK2^(V617F)and suggest further development and optimization towards clinical application in managing myeloproliferative neoplasms.
文摘BACKGROUND Endoscopic therapy is the primary approach for treating Mallory-Weiss syndro-me,particularly under conditions of mucosal protection and gastric acid suppre-ssion.However,for a subset of patients who cannot undergo endoscopic interven-tion or for whom such treatment proves ineffective,alternative measures like arterial embolization or surgical intervention may be required.While hyperbaric oxygen therapy(HBOT)has been applied across a range of medical conditions,its application in managing hemorrhage due to gastric tears remains undocumented.CASE SUMMARY A 52-year-old patient was admitted with symptoms of hematemesis and melena,and an endoscopy revealed a gastric fundus tear approximately 4 cm×5 cm in size.The lesion was considered unsuitable for endoscopic repair by the attending endoscopist.Despite conservative measures,including fasting and acid sup-pression,the patient experienced persistent bleeding and a substantial decrease in hemoglobin levels relative to admission values.Following a multidisciplinary consultation,HBOT was initiated,resulting in the cessation of bleeding and rapid wound healing.CONCLUSION For patients with gastric tears presenting with active hemorrhage,HBOT might offer an effective alternative when conventional endoscopic therapies are not viable or have been unsuccessful.
