Introduction Cancer treatment has been revolutionized with the advent of targeted therapy and immunotherapy.In the past,when cancer treatment modalities were restricted,conventional chemotherapy was the only option fo...Introduction Cancer treatment has been revolutionized with the advent of targeted therapy and immunotherapy.In the past,when cancer treatment modalities were restricted,conventional chemotherapy was the only option for systemic disease.Because chemotherapy empirically affects all dividing cells,the targets are virtually non-specific.In this regard,toxic effects on normal tissue are essentially inevitable.展开更多
The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating ...The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating cellular calcium balance,lipid metabolism,and cell death.Dysregulation of MAMs is involved in the development of chronic liver disease(CLD).In CLD,changes in MAMs structure and function occur due to factors such as cellular stress,inflammation,and oxidative stress,leading to abnormal interactions between mitochondria and the ER,resulting in liver cell injury,fibrosis,and impaired liver function.Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD.This paper reviews the literature on the association between mitochondria and the ER,as well as the intervention of traditional Chinese medicine in regulating CLD.展开更多
Point-of-care ultrasound(POCUS)of the internal jugular vein(IJV)offers a noninvasive means of estimating right atrial pressure(RAP),especially in cases where the inferior vena cava is inaccessible or unreliable due to...Point-of-care ultrasound(POCUS)of the internal jugular vein(IJV)offers a noninvasive means of estimating right atrial pressure(RAP),especially in cases where the inferior vena cava is inaccessible or unreliable due to conditions such as liver disease or abdominal surgery.While many clinicians are familiar with visually assessing jugular venous pressure through the internal jugular vein,this method lacks sensitivity.The utilization of POCUS significantly enhances the visualization of the vein,leading to a more accurate identification.It has been demonstrated that combining IJV POCUS with physical examination enhances the specificity of RAP estimation.This review aims to provide a comprehensive summary of the various sonographic techniques available for estimating RAP from the internal jugular vein,drawing upon existing data.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liv...Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liver disease varies substantially among populations.It is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with MASLD.Nonalcoholic steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of MASLD.MASLD diagnosis is based on the presence of steatosis,noninvasive scores and altered liver tests.Noninvasive scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely available.Currently,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical practice.Unfortunately,there is no definite pharmacological treatment for the condition.Creating public health policies to treat patients with risk factors for MASLD prevention is essential.展开更多
BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now...BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.CONCLUSION MASLD is a complex disease comprising epigenetic,genetic,and metabolic factors in its pathogenesis.Results vary across populations,gender,and age.Limited data exists on clinical practice guidelines for lean patients.Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.展开更多
Dementia is a syndrome with various underlying pathologies acting independently or in concert to cause cognitive dysfunction.The development of disease-specific treatments and targeted prevention strategies requires p...Dementia is a syndrome with various underlying pathologies acting independently or in concert to cause cognitive dysfunction.The development of disease-specific treatments and targeted prevention strategies requires precise clinical sub-typing via etiology and pathophysiological processes.Furthermore,recent research advances in biomarkers,especially for Alzheimer's disease(AD)diagnosis,have improved diagnostic precision for dementia.展开更多
The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer's disease pathogenesis and are considered the main pathological hallmarks of this devastating dis...The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer's disease pathogenesis and are considered the main pathological hallmarks of this devastating disease.Physiologically,these two proteins are produced and expressed within the normal human body.However,under pathological conditions,abnormal expression,posttranslational modifications,conformational changes,and truncation can make these proteins prone to aggregation,triggering specific disease-related cascades.Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases,such as Alzheimer's disease,Parkinson's disease,and amyotrophic lateral sclerosis,as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration.Additionally,these proteins have been linked to cardiovascular disease,cancer,traumatic brain injury,and diabetes,which are all leading causes of morbidity and mortality.In this comprehensive review,we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.展开更多
Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebr...Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.展开更多
BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the esta...BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.展开更多
The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction b...The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.展开更多
BACKGROUND In hepatology,the clinical use of endoscopic ultrasound(EUS)has experienced a notable increase in recent times.These applications range from the diagnosis to the treatment of various liver diseases.Therefor...BACKGROUND In hepatology,the clinical use of endoscopic ultrasound(EUS)has experienced a notable increase in recent times.These applications range from the diagnosis to the treatment of various liver diseases.Therefore,this systematic review summarizes the evidence for the diagnostic and therapeutic roles of EUS in liver diseases.AIM To examine and summarize the current available evidence of the possible roles of the EUS in making a suitable diagnosis in liver diseases as well as the therapeutic accuracy and efficacy.METHODS PubMed,Medline,Cochrane Library,Web of Science,and Google Scholar databases were extensively searched until October 2023.The methodological quality of the eligible articles was assessed using the Newcastle-Ottawa scale or Cochrane Risk of Bias tool.In addition,statistical analyses were performed using the Comprehensive Meta-Analysis software.RESULTS Overall,45 articles on EUS were included(28 on diagnostic role and 17 on therapeutic role).Pooled analysis demonstrated that EUS diagnostic tests had an accuracy of 92.4%for focal liver lesions(FLL)and 96.6%for parenchymal liver diseases.EUS-guided liver biopsies with either fine needle aspiration or fine needle biopsy had low complication rates when sampling FLL and parenchymal liver diseases(3.1%and 8.7%,respectively).Analysis of data from four studies showed that EUS-guided liver abscess had high clinical(90.7%)and technical success(90.7%)without significant complications.Similarly,EUS-guided interventions for the treatment of gastric varices(GV)have high technical success(98%)and GV obliteration rate(84%)with few complications(15%)and rebleeding events(17%).CONCLUSION EUS in liver diseases is a promising technique with the potential to be considered a first-line therapeutic and diagnostic option in selected cases.展开更多
Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory enshea...Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.展开更多
Background:Atrial septal defect(ASD)is a common form of adult congenital heart disease that can lead to long-term adverse outcomes if left untreated.Early closure of ASD has been associated with excellent outcomes and...Background:Atrial septal defect(ASD)is a common form of adult congenital heart disease that can lead to long-term adverse outcomes if left untreated.Early closure of ASD has been associated with excellent outcomes and lower complication rates.However,there is limited evidence regarding the prognosis of ASD closure in older adults.This study aims to evaluate the mortality rates in older ASD patients with and without closure.Methods:A retrospective cohort study was conducted on patients aged 40 years or older with ASD between 2001 and 2017.Patients were followed up to assess all-cause mortality.Univariable and multivariable analyses were performed to identify the predictors of mortality.A p-value of<0.05 was considered statistically significant.Results:The cohort consisted of 450 patients(mean age 56.6±10.4 years,77.3%female),with 66%aged between 40 and 60 years,and 34%over 60 years.Within the cohort,299 underwent ASD closure(201 with transcatheter and 98 with surgical closure).During the median follow-up duration of 7.9 years,51 patients died.The unadjusted cumulative 10-year rate of mortality was 3%in patients with ASD closure,and 28%in patients without ASD closure(log-rank p<0.001).Multivariable analysis revealed that age(hazard ratio[HR]1.04,95%confidence interval[CI]1.006–1.06,p=0.01),NYHA class(HR 2.75,95%CI 1.63–4.62,p<0.001),blood urea nitrogen(BUN)(HR 1.07,95%CI 1.03–1.12,p<0.001),right ventricular systolic pressure(RVSP)(HR 1.07,95%CI 1.003–1.04,p=0.01),and lack of ASD closure(HR 15.12,95%CI 5.63–40.59,p<0.001)were independently associated with mortality.Conclusion:ASD closure demonstrated favorable outcomes in older patients.Age,NYHA class,BUN,RVSP,and lack of ASD closure were identified as independent factors linked to mortality in this population.展开更多
Upper gastrointestinal bleeding(UGIB)can be attributed to either non-variceal or variceal causes.The latter is more aggressive with hemodynamic instability secondary to decompensated cirrhosis and portal hypertension....Upper gastrointestinal bleeding(UGIB)can be attributed to either non-variceal or variceal causes.The latter is more aggressive with hemodynamic instability secondary to decompensated cirrhosis and portal hypertension.Non-variceal UGIB(NVUGIB)occurs due to impaired gastroprotective mechanisms attributed to several drugs such as anticoagulants and nonsteroidal anti-inflammatory drugs.Helicobacter pylori infection contributes to the development of peptic ulcer bleeding as well.NVUGIB presentation can be either hemodynamically stable or unstable.During the initial assessment a scoring system including patient-related factors(current cardiac,renal,and liver diseases and hemodynamic and labo-ratory parameters)is used to determine the patient’s prognosis.The Glasgow Blatchford score has been shown to be the most useful and precise.Those with high-risk NVUGIB require urgent assessment and upper endoscopy to achieve better short-term and long-term outcomes such as less hospitalization,blood transfusion,and surgery.展开更多
Rationale:Adrenal histoplasmosis can present as bilateral adrenal enlargement with constitutional symptoms and/or adrenal insufficiency.Often these patients are initially investigated as secondary adrenal metastases b...Rationale:Adrenal histoplasmosis can present as bilateral adrenal enlargement with constitutional symptoms and/or adrenal insufficiency.Often these patients are initially investigated as secondary adrenal metastases before eventually their diagnosis established by histopathological examination of the adrenal tissues.Patients concerns:We report 4 cases of patients aged 55-78 who presented with hypocortisolism and bilateral adrenal masses.Diagnoses:Bilateral adrenal histoplasmosis.Interventions:Three patients received antifungal treatment for at least one year while 1 patient passed away before the initiation of antifungal treatment.Outcomes:Two patients’adrenal function recovered not requiring any steroid replacement,while 1 patient still requires long-term steroid replacement.Lessons:Adrenal histoplasmosis should be excluded in patients from endemic areas presenting with bilateral adrenal masses and adrenal insufficiency.Usually patients have an exposure to bird droppings,bat guano or soil contaminated with histoplasmosis fungi.Histopathological examination of biopsied adrenal tissues is still the gold standard investigation as serology and molecular diagnostic methods are still not widely available in most centers in Malaysia.展开更多
Viral hepatitis represents a major danger to public health,and is a globally leading cause of death.The five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis...Viral hepatitis represents a major danger to public health,and is a globally leading cause of death.The five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis E virus,each have their own unique epidemiology,structural biology,transmission,endemic patterns,risk of liver complications,and response to antiviral therapies.There remain few options for treatment,in spite of the increasing prevalence of viral-hepatitiscaused liver disease.Furthermore,chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality,even though effective treatments are available that could reduce or prevent most patients’complications.In 2016,the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030,along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis.Today,treatment is sufficiently able to prevent the disease from reaching advanced phases.However,future therapies must be extremely safe,and should ideally limit the period of treatment necessary.A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis.This review aims to summarize the current state of knowledge on each type of viral hepatitis,together with major innovations.展开更多
Cardiac arrest poses a significant global public health challenge,manifesting in approximately 550,000 cases annually within the United States.[1]In-hospital cardiac arrest(IHCA)is commonly attributed to airways and r...Cardiac arrest poses a significant global public health challenge,manifesting in approximately 550,000 cases annually within the United States.[1]In-hospital cardiac arrest(IHCA)is commonly attributed to airways and respiratory issues.[2]Recommendations emphasize the expertise of responders in airway management.[3]Various options exist,such as chest compression-only cardiopulmonary resuscitation(CPR),bag-mask ventilation(BMV),and advanced airways.The BMV and advanced airways are not deemed equivalent or superior based on previous evidence.[4]Achieving consistency in choosing and timing the optimal airway approach during IHCA is crucial.The current American Heart Association guidelines suggest an advanced airway strategy when endotracheal intubation(ETI)success rates are high,but the optimal time for advanced airway management remains unclear.[5]Wong et al[6]revealed that survival improved by less than 5 min with advanced airway management.According to a subgroup analysis of IHCA patients in emergency departments(EDs),early intubation was associated with a 1.5-fold greater rate of return of spontaneous circulation(ROSC)than in other locations.[7]ED patients’constant monitoring and immediate management,with readily available intubation equipment,enhance early intubation and survival rates.[6]Nonetheless,IHCA patients intubated within the first 15 min had a lower ROSC rate.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
Background Broilers have a robust metabolism and high body temperature,which make them less tolerant to hightemperature(HT)environments and more susceptible to challenges from elevated temperatures.Gut microbes,functi...Background Broilers have a robust metabolism and high body temperature,which make them less tolerant to hightemperature(HT)environments and more susceptible to challenges from elevated temperatures.Gut microbes,functioning as symbionts within the host,possess the capacity to significantly regulate the physiological functions and environmental adaptability of the host.This study aims to investigate the effects of gut microbial intervention on the body temperature and thermogenesis of broilers at different ambient temperatures,as well as the underlying mechanism involving the"gut-brain"axis.Methods Broilers were subjected to gut microbiota interference with or without antibiotics(control or ABX)starting at 1 day of age.At 21 day of age,they were divided into 4 groups and exposed to different environments for 7 d:The control and ABX groups at room temperature(RT,24±1℃,60%relative humidity(RH),24 h/d)and the control-HT and ABX-HT groups at high temperature(HT,32±1℃,60%RH,24 h/d).Results The results demonstrated that the antibiotic-induced gut microbiota intervention increased body weight and improved feed conversion in broiler chickens(P<0.05).Under HT conditions,the microbiota intervention reduced the rectal temperature of broiler chickens(P<0.05),inhibited the expression of avUCP and thermogenesisrelated genes in breast muscle and liver(P<0.05),and thus decreased thermogenesis capacity.Furthermore,the gut microbiota intervention blunted the hypothalamic‒pituitary‒adrenal axis and hypothalamic–pituitary–thyroid axis activation induced by HT conditions.By analyzing the cecal microbiota composition of control and ABX chickens maintained under HT conditions,we found that Alistipes was enriched in control chickens.In contrast,antibioticinduced gut microbiota intervention resulted in a decrease in the relative abundance of Alistipes(P<0.05).Moreover,this difference was accompanied by increased hypothalamic 5-hydroxytryptamine(5-HT)content and TPH2 expression(P<0.05).Conclusions These findings underscore the critical role of the gut microbiota in regulating broiler thermogenesis via the gut-brain axis and suggest that the hypothalamic 5-HT pathway may be a potential mechanism by which the gut microbiota affects thermoregulation in broilers.展开更多
In this editorial,we comment on the article by Zhang et al entitled Development of a machine learning-based model for predicting the risk of early postoperative recurrence of hepatocellular carcinoma.Hepatocellular ca...In this editorial,we comment on the article by Zhang et al entitled Development of a machine learning-based model for predicting the risk of early postoperative recurrence of hepatocellular carcinoma.Hepatocellular carcinoma(HCC),which is characterized by high incidence and mortality rates,remains a major global health challenge primarily due to the critical issue of postoperative recurrence.Early recurrence,defined as recurrence that occurs within 2 years posttreatment,is linked to the hidden spread of the primary tumor and significantly impacts patient survival.Traditional predictive factors,including both patient-and treatment-related factors,have limited predictive ability with respect to HCC recurrence.The integration of machine learning algorithms is fueled by the exponential growth of computational power and has revolutionized HCC research.The study by Zhang et al demonstrated the use of a groundbreaking preoperative prediction model for early postoperative HCC recurrence.Challenges persist,including sample size constraints,issues with handling data,and the need for further validation and interpretability.This study emphasizes the need for collaborative efforts,multicenter studies and comparative analyses to validate and refine the model.Overcoming these challenges and exploring innovative approaches,such as multi-omics integration,will enhance personalized oncology care.This study marks a significant stride toward precise,efficient,and personalized oncology practices,thus offering hope for improved patient outcomes in the field of HCC treatment.展开更多
文摘Introduction Cancer treatment has been revolutionized with the advent of targeted therapy and immunotherapy.In the past,when cancer treatment modalities were restricted,conventional chemotherapy was the only option for systemic disease.Because chemotherapy empirically affects all dividing cells,the targets are virtually non-specific.In this regard,toxic effects on normal tissue are essentially inevitable.
基金Supported by the National Natural Science Foundation of China,No.82204755,and No.81960751the Guangxi Natural Science Foundation Youth Project,No.2023GXNSFBA026274+1 种基金the Guangxi University of Traditional Chinese Medicine School-level Project Youth Fund,No.2022QN008Faculty of Chinese Medicine Science Guangxi University of Chinese Medicine Research Project,No.2022MS008 and No.2022QJ001.
文摘The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating cellular calcium balance,lipid metabolism,and cell death.Dysregulation of MAMs is involved in the development of chronic liver disease(CLD).In CLD,changes in MAMs structure and function occur due to factors such as cellular stress,inflammation,and oxidative stress,leading to abnormal interactions between mitochondria and the ER,resulting in liver cell injury,fibrosis,and impaired liver function.Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD.This paper reviews the literature on the association between mitochondria and the ER,as well as the intervention of traditional Chinese medicine in regulating CLD.
文摘Point-of-care ultrasound(POCUS)of the internal jugular vein(IJV)offers a noninvasive means of estimating right atrial pressure(RAP),especially in cases where the inferior vena cava is inaccessible or unreliable due to conditions such as liver disease or abdominal surgery.While many clinicians are familiar with visually assessing jugular venous pressure through the internal jugular vein,this method lacks sensitivity.The utilization of POCUS significantly enhances the visualization of the vein,leading to a more accurate identification.It has been demonstrated that combining IJV POCUS with physical examination enhances the specificity of RAP estimation.This review aims to provide a comprehensive summary of the various sonographic techniques available for estimating RAP from the internal jugular vein,drawing upon existing data.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liver disease varies substantially among populations.It is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with MASLD.Nonalcoholic steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of MASLD.MASLD diagnosis is based on the presence of steatosis,noninvasive scores and altered liver tests.Noninvasive scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely available.Currently,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical practice.Unfortunately,there is no definite pharmacological treatment for the condition.Creating public health policies to treat patients with risk factors for MASLD prevention is essential.
文摘BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.CONCLUSION MASLD is a complex disease comprising epigenetic,genetic,and metabolic factors in its pathogenesis.Results vary across populations,gender,and age.Limited data exists on clinical practice guidelines for lean patients.Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.
基金supported by the Japan Society for the Promotion of Science Overseas Research Fellow,the fellowship of Astellas Foundation for Research on Metabolic Disorders and the Japanese Society of Neurology grants for overseas study“Young Researcher Overseas Training Program” (SH)and NHMRC CRE grant 2006765 (to PSS)。
文摘Dementia is a syndrome with various underlying pathologies acting independently or in concert to cause cognitive dysfunction.The development of disease-specific treatments and targeted prevention strategies requires precise clinical sub-typing via etiology and pathophysiological processes.Furthermore,recent research advances in biomarkers,especially for Alzheimer's disease(AD)diagnosis,have improved diagnostic precision for dementia.
文摘The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer's disease pathogenesis and are considered the main pathological hallmarks of this devastating disease.Physiologically,these two proteins are produced and expressed within the normal human body.However,under pathological conditions,abnormal expression,posttranslational modifications,conformational changes,and truncation can make these proteins prone to aggregation,triggering specific disease-related cascades.Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases,such as Alzheimer's disease,Parkinson's disease,and amyotrophic lateral sclerosis,as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration.Additionally,these proteins have been linked to cardiovascular disease,cancer,traumatic brain injury,and diabetes,which are all leading causes of morbidity and mortality.In this comprehensive review,we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.
文摘Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.
文摘BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.
基金supported in part by the Japan Agency for Medical Research and Development (AMED) under grant number JP20ek0410073, JP23ek0410108, JP22ek0410100, AMEDCREST under grant number JP19gm1210008 and AMED-PRIME under grant number JP21gm6310029, the AMED Japan Initiative for World leading Vaccine Research and Development Centers (JP223fa627001)Japan Society for the Promotion of Science (JSPS): Scientific Research S (21H05046), Scientific Research B (21H03104, 22H03195, and 22H02844) and Challenging Research (20K21515 and 21K18254)+3 种基金the JST FOREST Program (JPMJFR2261, JPMJFR205Z)Y.A. was supported by a JSPS Research Fellowship for Young Scientists (23KJ1949)Japanese Society for Immunology (JSI)Kibou Scholarship for Doctoral Students in Immunology。
文摘The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.
文摘BACKGROUND In hepatology,the clinical use of endoscopic ultrasound(EUS)has experienced a notable increase in recent times.These applications range from the diagnosis to the treatment of various liver diseases.Therefore,this systematic review summarizes the evidence for the diagnostic and therapeutic roles of EUS in liver diseases.AIM To examine and summarize the current available evidence of the possible roles of the EUS in making a suitable diagnosis in liver diseases as well as the therapeutic accuracy and efficacy.METHODS PubMed,Medline,Cochrane Library,Web of Science,and Google Scholar databases were extensively searched until October 2023.The methodological quality of the eligible articles was assessed using the Newcastle-Ottawa scale or Cochrane Risk of Bias tool.In addition,statistical analyses were performed using the Comprehensive Meta-Analysis software.RESULTS Overall,45 articles on EUS were included(28 on diagnostic role and 17 on therapeutic role).Pooled analysis demonstrated that EUS diagnostic tests had an accuracy of 92.4%for focal liver lesions(FLL)and 96.6%for parenchymal liver diseases.EUS-guided liver biopsies with either fine needle aspiration or fine needle biopsy had low complication rates when sampling FLL and parenchymal liver diseases(3.1%and 8.7%,respectively).Analysis of data from four studies showed that EUS-guided liver abscess had high clinical(90.7%)and technical success(90.7%)without significant complications.Similarly,EUS-guided interventions for the treatment of gastric varices(GV)have high technical success(98%)and GV obliteration rate(84%)with few complications(15%)and rebleeding events(17%).CONCLUSION EUS in liver diseases is a promising technique with the potential to be considered a first-line therapeutic and diagnostic option in selected cases.
基金supported by the Spanish Ministry of Economy and Competitiveness,No.PID2019-106498GB-I00(to MVS)the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”,No.PI19/00071(to MAB)+1 种基金Ministerio de Ciencia e Innovación Project,No.SAF2017-82736-C2-1-R(to MTMF)in Universidad Autónoma de MadridFundación Universidad Francisco de Vitoria(to JS)。
文摘Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.
基金This study was approved by the Siriraj Institutional Review Board(SIRB),Faculty of Medicine Siriraj Hospital,Mahidol University(COA no.Si 760/2021).The need for consent was waived by the board due to its retrospective nature and as all personal identifying information was obliterated.The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki.
文摘Background:Atrial septal defect(ASD)is a common form of adult congenital heart disease that can lead to long-term adverse outcomes if left untreated.Early closure of ASD has been associated with excellent outcomes and lower complication rates.However,there is limited evidence regarding the prognosis of ASD closure in older adults.This study aims to evaluate the mortality rates in older ASD patients with and without closure.Methods:A retrospective cohort study was conducted on patients aged 40 years or older with ASD between 2001 and 2017.Patients were followed up to assess all-cause mortality.Univariable and multivariable analyses were performed to identify the predictors of mortality.A p-value of<0.05 was considered statistically significant.Results:The cohort consisted of 450 patients(mean age 56.6±10.4 years,77.3%female),with 66%aged between 40 and 60 years,and 34%over 60 years.Within the cohort,299 underwent ASD closure(201 with transcatheter and 98 with surgical closure).During the median follow-up duration of 7.9 years,51 patients died.The unadjusted cumulative 10-year rate of mortality was 3%in patients with ASD closure,and 28%in patients without ASD closure(log-rank p<0.001).Multivariable analysis revealed that age(hazard ratio[HR]1.04,95%confidence interval[CI]1.006–1.06,p=0.01),NYHA class(HR 2.75,95%CI 1.63–4.62,p<0.001),blood urea nitrogen(BUN)(HR 1.07,95%CI 1.03–1.12,p<0.001),right ventricular systolic pressure(RVSP)(HR 1.07,95%CI 1.003–1.04,p=0.01),and lack of ASD closure(HR 15.12,95%CI 5.63–40.59,p<0.001)were independently associated with mortality.Conclusion:ASD closure demonstrated favorable outcomes in older patients.Age,NYHA class,BUN,RVSP,and lack of ASD closure were identified as independent factors linked to mortality in this population.
文摘Upper gastrointestinal bleeding(UGIB)can be attributed to either non-variceal or variceal causes.The latter is more aggressive with hemodynamic instability secondary to decompensated cirrhosis and portal hypertension.Non-variceal UGIB(NVUGIB)occurs due to impaired gastroprotective mechanisms attributed to several drugs such as anticoagulants and nonsteroidal anti-inflammatory drugs.Helicobacter pylori infection contributes to the development of peptic ulcer bleeding as well.NVUGIB presentation can be either hemodynamically stable or unstable.During the initial assessment a scoring system including patient-related factors(current cardiac,renal,and liver diseases and hemodynamic and labo-ratory parameters)is used to determine the patient’s prognosis.The Glasgow Blatchford score has been shown to be the most useful and precise.Those with high-risk NVUGIB require urgent assessment and upper endoscopy to achieve better short-term and long-term outcomes such as less hospitalization,blood transfusion,and surgery.
文摘Rationale:Adrenal histoplasmosis can present as bilateral adrenal enlargement with constitutional symptoms and/or adrenal insufficiency.Often these patients are initially investigated as secondary adrenal metastases before eventually their diagnosis established by histopathological examination of the adrenal tissues.Patients concerns:We report 4 cases of patients aged 55-78 who presented with hypocortisolism and bilateral adrenal masses.Diagnoses:Bilateral adrenal histoplasmosis.Interventions:Three patients received antifungal treatment for at least one year while 1 patient passed away before the initiation of antifungal treatment.Outcomes:Two patients’adrenal function recovered not requiring any steroid replacement,while 1 patient still requires long-term steroid replacement.Lessons:Adrenal histoplasmosis should be excluded in patients from endemic areas presenting with bilateral adrenal masses and adrenal insufficiency.Usually patients have an exposure to bird droppings,bat guano or soil contaminated with histoplasmosis fungi.Histopathological examination of biopsied adrenal tissues is still the gold standard investigation as serology and molecular diagnostic methods are still not widely available in most centers in Malaysia.
基金Supported by the JSPS Kakenhi Grant,No.JP24K15491.
文摘Viral hepatitis represents a major danger to public health,and is a globally leading cause of death.The five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis E virus,each have their own unique epidemiology,structural biology,transmission,endemic patterns,risk of liver complications,and response to antiviral therapies.There remain few options for treatment,in spite of the increasing prevalence of viral-hepatitiscaused liver disease.Furthermore,chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality,even though effective treatments are available that could reduce or prevent most patients’complications.In 2016,the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030,along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis.Today,treatment is sufficiently able to prevent the disease from reaching advanced phases.However,future therapies must be extremely safe,and should ideally limit the period of treatment necessary.A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis.This review aims to summarize the current state of knowledge on each type of viral hepatitis,together with major innovations.
基金granted by the Faculty of Medicine,Chiang Mai University(Grant No.MC017-65)supported by the National Center for Advancing Translational Sciences,National Institutes of Health,through grant number UL1 TR001860(to WW).
文摘Cardiac arrest poses a significant global public health challenge,manifesting in approximately 550,000 cases annually within the United States.[1]In-hospital cardiac arrest(IHCA)is commonly attributed to airways and respiratory issues.[2]Recommendations emphasize the expertise of responders in airway management.[3]Various options exist,such as chest compression-only cardiopulmonary resuscitation(CPR),bag-mask ventilation(BMV),and advanced airways.The BMV and advanced airways are not deemed equivalent or superior based on previous evidence.[4]Achieving consistency in choosing and timing the optimal airway approach during IHCA is crucial.The current American Heart Association guidelines suggest an advanced airway strategy when endotracheal intubation(ETI)success rates are high,but the optimal time for advanced airway management remains unclear.[5]Wong et al[6]revealed that survival improved by less than 5 min with advanced airway management.According to a subgroup analysis of IHCA patients in emergency departments(EDs),early intubation was associated with a 1.5-fold greater rate of return of spontaneous circulation(ROSC)than in other locations.[7]ED patients’constant monitoring and immediate management,with readily available intubation equipment,enhance early intubation and survival rates.[6]Nonetheless,IHCA patients intubated within the first 15 min had a lower ROSC rate.
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.
基金the National Natural Science Foundation of China,grant numbers 32372935,32072781.
文摘Background Broilers have a robust metabolism and high body temperature,which make them less tolerant to hightemperature(HT)environments and more susceptible to challenges from elevated temperatures.Gut microbes,functioning as symbionts within the host,possess the capacity to significantly regulate the physiological functions and environmental adaptability of the host.This study aims to investigate the effects of gut microbial intervention on the body temperature and thermogenesis of broilers at different ambient temperatures,as well as the underlying mechanism involving the"gut-brain"axis.Methods Broilers were subjected to gut microbiota interference with or without antibiotics(control or ABX)starting at 1 day of age.At 21 day of age,they were divided into 4 groups and exposed to different environments for 7 d:The control and ABX groups at room temperature(RT,24±1℃,60%relative humidity(RH),24 h/d)and the control-HT and ABX-HT groups at high temperature(HT,32±1℃,60%RH,24 h/d).Results The results demonstrated that the antibiotic-induced gut microbiota intervention increased body weight and improved feed conversion in broiler chickens(P<0.05).Under HT conditions,the microbiota intervention reduced the rectal temperature of broiler chickens(P<0.05),inhibited the expression of avUCP and thermogenesisrelated genes in breast muscle and liver(P<0.05),and thus decreased thermogenesis capacity.Furthermore,the gut microbiota intervention blunted the hypothalamic‒pituitary‒adrenal axis and hypothalamic–pituitary–thyroid axis activation induced by HT conditions.By analyzing the cecal microbiota composition of control and ABX chickens maintained under HT conditions,we found that Alistipes was enriched in control chickens.In contrast,antibioticinduced gut microbiota intervention resulted in a decrease in the relative abundance of Alistipes(P<0.05).Moreover,this difference was accompanied by increased hypothalamic 5-hydroxytryptamine(5-HT)content and TPH2 expression(P<0.05).Conclusions These findings underscore the critical role of the gut microbiota in regulating broiler thermogenesis via the gut-brain axis and suggest that the hypothalamic 5-HT pathway may be a potential mechanism by which the gut microbiota affects thermoregulation in broilers.
文摘In this editorial,we comment on the article by Zhang et al entitled Development of a machine learning-based model for predicting the risk of early postoperative recurrence of hepatocellular carcinoma.Hepatocellular carcinoma(HCC),which is characterized by high incidence and mortality rates,remains a major global health challenge primarily due to the critical issue of postoperative recurrence.Early recurrence,defined as recurrence that occurs within 2 years posttreatment,is linked to the hidden spread of the primary tumor and significantly impacts patient survival.Traditional predictive factors,including both patient-and treatment-related factors,have limited predictive ability with respect to HCC recurrence.The integration of machine learning algorithms is fueled by the exponential growth of computational power and has revolutionized HCC research.The study by Zhang et al demonstrated the use of a groundbreaking preoperative prediction model for early postoperative HCC recurrence.Challenges persist,including sample size constraints,issues with handling data,and the need for further validation and interpretability.This study emphasizes the need for collaborative efforts,multicenter studies and comparative analyses to validate and refine the model.Overcoming these challenges and exploring innovative approaches,such as multi-omics integration,will enhance personalized oncology care.This study marks a significant stride toward precise,efficient,and personalized oncology practices,thus offering hope for improved patient outcomes in the field of HCC treatment.