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
Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains uncle...Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.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
Objective:To explore the therapeutic effect of double-puncture tympanic membrane puncture and tympanic cavity drug injection in patients with acute secretory otitis media.Methods:A total of 84 patients with acute secr...Objective:To explore the therapeutic effect of double-puncture tympanic membrane puncture and tympanic cavity drug injection in patients with acute secretory otitis media.Methods:A total of 84 patients with acute secretory otitis media admitted to our hospital from June 2024 to June 2025 were selected and randomly divided into two groups by drawing lots.The control group(42 cases)was treated with the traditional single-puncture tympanic membrane puncture and tympanic cavity drug injection method,while the observation group(42 cases)was treated with the double-puncture tympanic membrane puncture and tympanic cavity drug injection method.The therapeutic effects of the two groups were compared.Results:The overall treatment response rate,overall complication rate,time to symptom relief,and improvement in hearing threshold in the observation group were all superior to those in the control group,with statistically significant differences(P<0.05).Conclusion:For acute secretory otitis media,the treatment method of double-puncture tympanic membrane puncture and tympanic cavity drug injection demonstrates definite efficacy,significantly reducing the incidence of complications,accelerating symptom relief,and improving hearing function,making it worthy of promotion.展开更多
Ossiculoplasty remains a challenging surgical procedure,with outcomes heavily influenced by diverse anatomical and pathological factors.Over the decades,numerous scoring systems have been developed to predict the prog...Ossiculoplasty remains a challenging surgical procedure,with outcomes heavily influenced by diverse anatomical and pathological factors.Over the decades,numerous scoring systems have been developed to predict the prognosis of ossiculoplasty,each emphasizing different variables such as ossicular status,middle ear environment,and surgical history.This paper provides a comprehensive review of the evolution of prognostic scoring systems,including Austin's original ossicular classification,Bellucci's otorrhea staging,the Middle Ear Risk Index(MERI),the Ossiculoplasty Outcome Parameter Staging(OOPS),and the recently introduced Ear Environment Risk(EER)scale.While these systems have significantly contributed to preoperative assessment,each presents notable limitations in encompassing all variables affecting surgical success.Therefore,the aim of this paper is to provide a review of the ossiculoplasty prognostic scores and show the benefits,innovations and gaps associated with each.To address these gaps,a novel,modified scoring system is proposed,incorporating previously overlooked but clinically significant factors such as tympanic membrane status,type of tympanoplasty,ossicular replacement material,CT scan findings,and the presence of complicated ear conditions.By synthesizing elements from historical scores with updated clinical insights,the proposed system aims to provide a more holistic and predictive framework for preoperative evaluation.Future multicenter studies are encouraged to validate the efficacy and prognostic power of this new scoring system,with the goal of improving surgical planning and patient counseling in ossiculoplasty.展开更多
Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury respons...Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.展开更多
Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognost...Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognostic biomarker in LA-LSCC.Methods:miR-449a expression was analyzed in tumor tissues,adjacent normal tissues,and serum from 81 LA-LSCC patients and 50 controls using quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).We assessed the diagnostic accuracy by Receiver Operating Characteristic curve(ROC curves),clinicopathological associations,survival outcomes(Kaplan-Meier),and treatment response dynamics.Results:miR-449a was significantly downregulated in LA-LSCC tissues(p<0.0001)and serum(p<0.0001),with a strong tissue-serum correlation(R^(2)=0.988).Tissue miR-449a demonstrated a diagnostic accuracy(Area Under the Curve,AUC=0.857),while serum showed moderate accuracy(AUC=0.734).High miR-449a expression correlated with favorable clinicopathological features and improved survival(median overall survival:67.82 vs.23.74 months;p=0.0012).Multivariate analysis confirmed miR-449a as an independent prognostic factor(p<0.001).miR-449a levels increased post-treatment,particularly in responders to chemotherapy/radiation(p<0.0001).Conclusion:miR-449a serves as a non-invasive biomarker for LA-LSCC diagnosis,prognosis,and treatment monitoring.Its dynamic expression highlights potential for risk stratification and therapy response prediction,warranting further validation in larger cohorts.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
Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor ...Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.展开更多
The cloud-fog computing paradigm has emerged as a novel hybrid computing model that integrates computational resources at both fog nodes and cloud servers to address the challenges posed by dynamic and heterogeneous c...The cloud-fog computing paradigm has emerged as a novel hybrid computing model that integrates computational resources at both fog nodes and cloud servers to address the challenges posed by dynamic and heterogeneous computing networks.Finding an optimal computational resource for task offloading and then executing efficiently is a critical issue to achieve a trade-off between energy consumption and transmission delay.In this network,the task processed at fog nodes reduces transmission delay.Still,it increases energy consumption,while routing tasks to the cloud server saves energy at the cost of higher communication delay.Moreover,the order in which offloaded tasks are executed affects the system’s efficiency.For instance,executing lower-priority tasks before higher-priority jobs can disturb the reliability and stability of the system.Therefore,an efficient strategy of optimal computation offloading and task scheduling is required for operational efficacy.In this paper,we introduced a multi-objective and enhanced version of Cheeta Optimizer(CO),namely(MoECO),to jointly optimize the computation offloading and task scheduling in cloud-fog networks to minimize two competing objectives,i.e.,energy consumption and communication delay.MoECO first assigns tasks to the optimal computational nodes and then the allocated tasks are scheduled for processing based on the task priority.The mathematical modelling of CO needs improvement in computation time and convergence speed.Therefore,MoECO is proposed to increase the search capability of agents by controlling the search strategy based on a leader’s location.The adaptive step length operator is adjusted to diversify the solution and thus improves the exploration phase,i.e.,global search strategy.Consequently,this prevents the algorithm from getting trapped in the local optimal solution.Moreover,the interaction factor during the exploitation phase is also adjusted based on the location of the prey instead of the adjacent Cheetah.This increases the exploitation capability of agents,i.e.,local search capability.Furthermore,MoECO employs a multi-objective Pareto-optimal front to simultaneously minimize designated objectives.Comprehensive simulations in MATLAB demonstrate that the proposed algorithm obtains multiple solutions via a Pareto-optimal front and achieves an efficient trade-off between optimization objectives compared to baseline methods.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
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 (32072936 and 32273080)。
文摘Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.
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.
文摘Objective:To explore the therapeutic effect of double-puncture tympanic membrane puncture and tympanic cavity drug injection in patients with acute secretory otitis media.Methods:A total of 84 patients with acute secretory otitis media admitted to our hospital from June 2024 to June 2025 were selected and randomly divided into two groups by drawing lots.The control group(42 cases)was treated with the traditional single-puncture tympanic membrane puncture and tympanic cavity drug injection method,while the observation group(42 cases)was treated with the double-puncture tympanic membrane puncture and tympanic cavity drug injection method.The therapeutic effects of the two groups were compared.Results:The overall treatment response rate,overall complication rate,time to symptom relief,and improvement in hearing threshold in the observation group were all superior to those in the control group,with statistically significant differences(P<0.05).Conclusion:For acute secretory otitis media,the treatment method of double-puncture tympanic membrane puncture and tympanic cavity drug injection demonstrates definite efficacy,significantly reducing the incidence of complications,accelerating symptom relief,and improving hearing function,making it worthy of promotion.
文摘Ossiculoplasty remains a challenging surgical procedure,with outcomes heavily influenced by diverse anatomical and pathological factors.Over the decades,numerous scoring systems have been developed to predict the prognosis of ossiculoplasty,each emphasizing different variables such as ossicular status,middle ear environment,and surgical history.This paper provides a comprehensive review of the evolution of prognostic scoring systems,including Austin's original ossicular classification,Bellucci's otorrhea staging,the Middle Ear Risk Index(MERI),the Ossiculoplasty Outcome Parameter Staging(OOPS),and the recently introduced Ear Environment Risk(EER)scale.While these systems have significantly contributed to preoperative assessment,each presents notable limitations in encompassing all variables affecting surgical success.Therefore,the aim of this paper is to provide a review of the ossiculoplasty prognostic scores and show the benefits,innovations and gaps associated with each.To address these gaps,a novel,modified scoring system is proposed,incorporating previously overlooked but clinically significant factors such as tympanic membrane status,type of tympanoplasty,ossicular replacement material,CT scan findings,and the presence of complicated ear conditions.By synthesizing elements from historical scores with updated clinical insights,the proposed system aims to provide a more holistic and predictive framework for preoperative evaluation.Future multicenter studies are encouraged to validate the efficacy and prognostic power of this new scoring system,with the goal of improving surgical planning and patient counseling in ossiculoplasty.
基金supported by the National Key Research and Development Program of China,No.2022YFC2704801(to CZhu)the National Natural Science Foundation of China,Nos.U21A20347(to CZhu),82203969(to YX),82371472(to XZ)+3 种基金Health Commission of Henan Province,Nos.SBGJ202303039(to XZ),SBGJ202301009(to CZhu),YQRC2024018(to XZ),YQRC2024019(to YX)Henan Science and Technology Department,Nos.242102311054(to XZ),241111521300(to CZhu),GZS2023003(to XW)Swedish Research Council,Nos.2022-01019(to CZhu),2021-01950(to XW)Swedish Governmental Grants to Scientists Working in Healthcare,Nos.ALFGBG-1005209(to CZhu),ALFBG-1005257(to XW),ALFGBG-965197(to CZhu).
文摘Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.
基金The authors extend their appreciation to Taif University,Saudi Arabia,for supporting this work through project No.(TU-DSPP-2024-54).
文摘Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognostic biomarker in LA-LSCC.Methods:miR-449a expression was analyzed in tumor tissues,adjacent normal tissues,and serum from 81 LA-LSCC patients and 50 controls using quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).We assessed the diagnostic accuracy by Receiver Operating Characteristic curve(ROC curves),clinicopathological associations,survival outcomes(Kaplan-Meier),and treatment response dynamics.Results:miR-449a was significantly downregulated in LA-LSCC tissues(p<0.0001)and serum(p<0.0001),with a strong tissue-serum correlation(R^(2)=0.988).Tissue miR-449a demonstrated a diagnostic accuracy(Area Under the Curve,AUC=0.857),while serum showed moderate accuracy(AUC=0.734).High miR-449a expression correlated with favorable clinicopathological features and improved survival(median overall survival:67.82 vs.23.74 months;p=0.0012).Multivariate analysis confirmed miR-449a as an independent prognostic factor(p<0.001).miR-449a levels increased post-treatment,particularly in responders to chemotherapy/radiation(p<0.0001).Conclusion:miR-449a serves as a non-invasive biomarker for LA-LSCC diagnosis,prognosis,and treatment monitoring.Its dynamic expression highlights potential for risk stratification and therapy response prediction,warranting further validation in larger cohorts.
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Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.
基金appreciation to the Princess Nourah bint Abdulrahman University Researchers Supporting Project number(PNURSP2025R384)Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘The cloud-fog computing paradigm has emerged as a novel hybrid computing model that integrates computational resources at both fog nodes and cloud servers to address the challenges posed by dynamic and heterogeneous computing networks.Finding an optimal computational resource for task offloading and then executing efficiently is a critical issue to achieve a trade-off between energy consumption and transmission delay.In this network,the task processed at fog nodes reduces transmission delay.Still,it increases energy consumption,while routing tasks to the cloud server saves energy at the cost of higher communication delay.Moreover,the order in which offloaded tasks are executed affects the system’s efficiency.For instance,executing lower-priority tasks before higher-priority jobs can disturb the reliability and stability of the system.Therefore,an efficient strategy of optimal computation offloading and task scheduling is required for operational efficacy.In this paper,we introduced a multi-objective and enhanced version of Cheeta Optimizer(CO),namely(MoECO),to jointly optimize the computation offloading and task scheduling in cloud-fog networks to minimize two competing objectives,i.e.,energy consumption and communication delay.MoECO first assigns tasks to the optimal computational nodes and then the allocated tasks are scheduled for processing based on the task priority.The mathematical modelling of CO needs improvement in computation time and convergence speed.Therefore,MoECO is proposed to increase the search capability of agents by controlling the search strategy based on a leader’s location.The adaptive step length operator is adjusted to diversify the solution and thus improves the exploration phase,i.e.,global search strategy.Consequently,this prevents the algorithm from getting trapped in the local optimal solution.Moreover,the interaction factor during the exploitation phase is also adjusted based on the location of the prey instead of the adjacent Cheetah.This increases the exploitation capability of agents,i.e.,local search capability.Furthermore,MoECO employs a multi-objective Pareto-optimal front to simultaneously minimize designated objectives.Comprehensive simulations in MATLAB demonstrate that the proposed algorithm obtains multiple solutions via a Pareto-optimal front and achieves an efficient trade-off between optimization objectives compared to baseline methods.
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.
