Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually wit...Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually with>20%mortality.Its progression involves metabolic imbalances,toxin accumulation,and multiorgan failure,often culminating in chronic kidney disease.Current therapies(fluid resuscitation,diuretics,renal replacement therapy)remain limited.Inflammation drives AKI pathogenesis:renal insults(ischemia,toxins)trigger tubular cell release of pro-inflammatory mediators(TNF-α,IL-1β,IL-6),activating neutrophil gelatinase-associated lipocalin(NGAL)and dysregulating P38 MAPK/ERK pathways.This cascade promotes leukocyte infiltration,oxidative stress,and apoptosis,exacerbating renal damage.Ononin,a flavonoid from Astragali Radix,shows multi-target potential by suppressing pro-inflammatory cytokines,modulating signaling,and mitigating oxidative stress.Its dual anti-inflammatory/antioxidant properties position it as a promising candidate for AKI intervention.Exploring the ameliorative effect of ononin on the inflammatory response Ameliorative effect of ononin on the inflammatory response in doxorubicin-induced AKI mice.Methods:We used network pharmacology to explore ononin’s target molecules and AKI-related disease molecules,identified their intersections,and predicted potential mechanisms via enrichment analysis,followed by molecular docking verification.For in-vivo validation,50 mice were randomly divided into five groups(n=10/group):Control,Model,Ononin-L(15 mg/kg),Ononin-H(60 mg/kg),and Dexamethasone(2.6 mg/kg).An AKI model was established by intravenous tail-vein injection of Doxorubicin(15 mg/kg).Samples were collected 12 h post-induction.We calculated the renal coefficient,examined renal histopathology using hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson’s trichrome(MASSON)staining,and observed mitochondrial morphology by electron microscopy(EM).ELISA was used to measure NGAL,serum creatinine(Scr),and blood urea nitrogen(BUN)levels in serum.Immunofluorescence(IF)evaluated the expression of P-P38,P-ERK,NGAL,and KIM-1 in renal tissues.RT-qPCR assessed the gene expression of pro-inflammatory cytokines,MAPK pathway components,and renal injury markers in kidney tissues.Western Blot(WB)quantified P-P38,P38 MAPK,P-ERK,ERK,NGAL,and KIM-1 in renal tissues.Results:Network pharmacology analysis suggested that ononin could attenuate AKI through its anti-inflammatory properties and regulation of the MAPK signaling pathway.The Model group exhibited a significantly elevated renal coefficient(P<0.05),severe histopathological damage,and mitochondrial dysfunction compared to controls.Serum levels of NGAL,Scr,and BUN were markedly increased(P<0.05),indicating impaired renal function.Enhanced fluorescence signals of P-P38 MAPK,P-ERK,NGAL,and KIM-1 suggested activation of MAPK pathways and renal injury.Upregulation of pro-inflammatory cytokines(IL-1β,IL-6,TNF-α)and MAPK-related genes(P38 MAPK,ERK)alongside injury markers(NGAL,KIM-1)(P<0.05).Increased ratios of phosphorylated-to-total proteins(P-P38/P38,P-ERK/ERK)and elevated NGAL/KIM-1 protein levels confirmed pathway dysregulation.Treatment significantly reduced the renal coefficient(P<0.05),attenuated histological damage,and restored mitochondrial integrity.NGAL,Scr,and BUN levels were lowered,reflecting functional recovery.Diminished fluorescence intensities of P-P38,P-ERK,NGAL,and KIM-1 indicated suppression of injury pathways.Downregulation of inflammatory cytokines(IL-1β,IL-6,TNF-α),MAPK components(P38 MAPK,ERK),and injury markers(NGAL,KIM-1)(P<0.05).Reduced phosphorylation ratios(P-P38/P38,P-ERK/ERK)and decreased NGAL/KIM-1 protein expression demonstrated therapeutic efficacy.Conclusion:Ononin ameliorates inflammatory responses in AKI mice via the P38 MAPK/ERK pathway.展开更多
Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)h...Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)has garnered increasing attention.Compared to AP caused by other causes,HTG-AP often has a more subtle onset but is more likely to progress to a severe,critical illness that poses a serious threat to a patient’s life and health.Research suggests a potential connection between the gut microbiota and AP,which could be mediated by bacterial metabolites,immune cells,and inflammatory factors.This is supported by observations of microbial imbalance and higher intestinal permeability in patients with AP.In addition,studies have shown that HTG-induced changes in gut microbiota can worsen AP by negatively impacting the host metabolism,immune response,and function of the intestinal barrier.In this review,we summarize recent clinical and animal studies on the role and mechanism of gut microbiota in the severity of AP aggravated by HTG.The application prospects of the newly proposed microbial-host-isozyme concept are summarized,focusing on its potential for the precision diagnosis and treatment of HTG-AP through gut microbiota regulation.展开更多
Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight ...Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.展开更多
Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genoty...Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.展开更多
AIM:To investigate the long-term outcomes in acute primary angle closure(APAC)patients treated with lens extraction(LE)surgery and to identify risk factors for glaucomatous optic neuropathy(GON).METHODS:In this longit...AIM:To investigate the long-term outcomes in acute primary angle closure(APAC)patients treated with lens extraction(LE)surgery and to identify risk factors for glaucomatous optic neuropathy(GON).METHODS:In this longitudinal observational study,detailed medical histories of APAC patients and comprehensive ophthalmic examinations at final followup were collected.Logistic regression analysis was performed to identify predictors of blindness.Univariate and multivariate linear regression analyses were conducted to determine risk factors associated with visual outcomes.RESULTS:This study included 39 affected eyes of 31 subjects(26 females)with an average age of 74.1±8.0y.At 6.7±4.2y after APAC attack,2(5.7%)eyes had bestcorrected visual acuity(VA)worse than 3/60.Advanced glaucomatous visual field loss was observed in 15(39.5%)affected eyes and 5(25.0%)fellow eyes.Nine affected eyes(23.7%)had GON,and 11(28.9%)were blind.Six(15.4%)affected eyes and 2(9.1%)fellow eyes had suspicious progression.A significantly higher blindness rate in factory workers compared to office workers.Logistic regression identified that worse VA at attack(OR 10.568,95%CI 1.288-86.695;P=0.028)and worse early postoperative VA(OR 13.214,95%CI 1.157-150.881;P=0.038)were risk factors for blindness.Multivariate regression showed that longer duration of elevated intraocular pressure(P=0.004)and worse early postoperative VA(P=0.009)were associated with worse visual outcomes.CONCLUSION:Despite LE surgery,some APAC patients experience continued visual function deterioration.Lifelong monitoring is necessary.Target pressure and progression rates should be re-evaluated during follow-up.展开更多
BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such a...BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.展开更多
Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal ce...Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.展开更多
Acute pancreatitis(AP)is a prevalent gastrointestinal disease necessitating hospitalization globally,with an annual incidence ranging from 13 to 45 per 100,000 individuals[1]and a mortality rate of 5%-10%.[2]While mos...Acute pancreatitis(AP)is a prevalent gastrointestinal disease necessitating hospitalization globally,with an annual incidence ranging from 13 to 45 per 100,000 individuals[1]and a mortality rate of 5%-10%.[2]While most cases follow a self-limiting course,approximately 20%-30%of cases progress to severe acute pancreatitis(SAP),characterized by pancreatic necrosis and multiorgan failure,with the mortality rate increasing to 36%-50%.展开更多
Acute respiratory distress syndrome(ARDS)is a severe clinical condition characterized by acute respiratory failure due to widespread pulmonary inflammation and edema.The incidence of ARDS among intensive care unit(ICU...Acute respiratory distress syndrome(ARDS)is a severe clinical condition characterized by acute respiratory failure due to widespread pulmonary inflammation and edema.The incidence of ARDS among intensive care unit(ICU)patients is approximately 10%,with mortality rates ranging from 35%to 45%and exceeding 50%in severe cases.[1]Identifying and controlling risk factors for ARDS is critical for early prevention.Smoking remains a significant global public health issue,affecting one-third of adults and 40%of children through exposure to secondhand smoke.[2]In an animal study,cigarette smoke impaired lung endothelial barrier function through oxidative stress and exacerbated lipopolysaccharide-induced increases in vascular permeability in vivo.This finding is consistent with the pathological changes observed in ARDS.[3]Although many observational studies have suggested a potential link between smoking and ARDS,the causal relationship remains unclear.This study uses Mendelian randomization(MR)to explore whether smoking behavior causally influences ARDS and investigates the mechanisms by which smoking may contribute to ARDS development through transcriptomic analysis of the Gene Expression Omnibus(GEO)database.展开更多
Acute fatty liver of pregnancy(AFLP)is a rare but potentially life-threatening liver disease associated with mitochondrial dysfunction.It is characterized by microvesicular hepatic steatosis and typically occurs in th...Acute fatty liver of pregnancy(AFLP)is a rare but potentially life-threatening liver disease associated with mitochondrial dysfunction.It is characterized by microvesicular hepatic steatosis and typically occurs in the third trimester,though it may rarely present postpartum.AFLP is considered a non-thrombotic microangiopathy(TMA)but may present with overlapping TMA features.Its incidence ranges from 1 in 7000 to 1 in 20000 pregnancies,although milder cases may go unrecognized.AFLP can rapidly progress to acute liver failure and 20%to 40%of affected women exhibit clinical features of preeclampsia.Acute kidney injury(AKI)is a frequent complication,observed in 55%to 75%of AFLP cases,which is significantly higher than the 7%to 20%occurrence seen in preeclampsia or hemolysis,elevated liver enzymes,and low platelets syndrome.The exact mechanism behind AKI in AFLP remains unclear,but renal histology has shown tubular deposits of free fatty acids,which correlate with current theories regarding liver pathology.While AFLP-associated AKI is often reversible after delivery,some patients may develop persistent AKI that requires dialysis.Therapeutic plasma exchange(TPE)has been explored in these cases,but available evidence is limited.This review summarizes the current understanding of the epidemiology,pathophysiology,clinical features,and management of AKI in the context of AFLP,and discusses the potential role of adjunctive therapies such as TPE.展开更多
BACKGROUND Acute disseminated encephalomyelitis(ADEM),which is rare,primarily affects children.It usually manifests as acute encephalopathy and multifocal neurological impairments after infection or vaccination.Diagno...BACKGROUND Acute disseminated encephalomyelitis(ADEM),which is rare,primarily affects children.It usually manifests as acute encephalopathy and multifocal neurological impairments after infection or vaccination.Diagnosis is still difficult due to the clinical and radiological similarity to other central nervous system disorders.Adult-onset ADEM calls for thorough reporting in order to improve diagnosis and treatment.CASE SUMMARY A 55-year-old man with hypertension had a high fever,intense headache and a steady decline in his neurological function after two weeks.Left facial paralysis was the initial symptom,which progressed to left hemiparesis,reduced consciousness level,photophobia,phonophobia,vomiting,and a focal seizure in the right leg.He had no history of autoimmune disease,vaccinations,or infections.Investigations showed negative infectious/autoimmune serology,mild cerebrospinal fluid lymphocytic pleocytosis(protein 76 mg/dL),and lymphopenia.Brain magnetic resonance imaging without contrast revealed bilateral,symmetrical T2/fluid-attenuated inversion recovery hyperintensities,primarily in the middle cerebellar peduncles,with minor involvement in the pontine and periventricular regions.Neoplastic,metabolic,vascular,and infectious conditions were not included.The patient showed spontaneous neurological improvement by Week 3 with near-complete motor recovery(limb strength 4/5)after methylprednisolone and rehabilitation,despite logistical delays in starting immunotherapy.The monophasic course and radiological/clinical remission were supported by idiopathic ADEM.CONCLUSION This case shows an uncommon,idiopathic,cerebellar-predominant ADEM variation in an adult without conventional triggers.It emphasizes the diagnostic difficulty in distinguishing ADEM from mimics(such as stroke or infection)in adults.Spontaneous improvement before treatment,although early detection is still crucial,should be highlighted,although early detection is still crucial.Increased clinician awareness,fair access to neuroimaging,and focused research on adult ADEM are crucial to fill these gaps and improve outcomes in places with limited resources.展开更多
BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HA...BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HAV,as evident by cases of acute hepatitis due to HAV among adults.AIM To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus(HEV)infection.METHODS This was a trend analysis conducted at Aga Khan University Hospital Karachi(Sindh,Pakistan)from February 2024 to May 2024.Individuals aged 18 years and older diagnosed with acute viral hepatitis attributed to hepatotropic viruses in 2024 were reviewed.To compare the trend patients admitted with acute hepatitis during 2019-2023 were also reviewed.Data regarding clinical and laboratory parameters were recorded.The yearly trend of acute hepatitis due to HAV and HEV was analyzed,and comparative analysis was done between HAV and HEV cases among adults.RESULTS A total of 396 patients were found to have acute hepatitis during our study duration.HAV was diagnosed in 234 patients(59%)while 157 patients(39.6%)were found to have acute HEV infection.Additionally,acute hepatitis B virus infection was identified in 3 patients(0.7%),whereas acute hepatitis C virus infection was found in 2(0.5%)cases of acute hepatitis.Yearly trends showed increasing occurrence of HAV infection among adults over last 5 years.The patients with acute HAV were younger than patients with HEV(28 years±8 years vs 30 years±8 years;P<0.01).Higher levels of total bilirubin were seen in HEV infection,while higher levels of alanine transaminase were seen in HAV infection.However,a higher proportion of acute liver failure(ALF),coagulopathy,and mortality were observed in HEV.CONCLUSION An increase in acute hepatitis A cases among adults shows less severity than hepatitis E,highlighting the need for better sanitation,hygiene,and adult hepatitis A vaccination programs.展开更多
BACKGROUND Simultaneous acute ischemic stroke(AIS)and myocardial infarction(cardio-cerebral ischemic attack)have rarely been reported in the literature.Currently,no clear evidence-based guidelines or clinical trials e...BACKGROUND Simultaneous acute ischemic stroke(AIS)and myocardial infarction(cardio-cerebral ischemic attack)have rarely been reported in the literature.Currently,no clear evidence-based guidelines or clinical trials exist to determine the optimal therapeutic strategy for these patients.CASE SUMMARY We present the case of a 27-year-old Chinese man who simultaneously experie-nced acute concomitant cerebrocardiac infarction(CCI)and painless ST-elevation myocardial infarction.The patient was successfully treated with elective percu-taneous coronary intervention(PCI)after receiving urgent systemic thrombolysis at the standard dose for AIS.CONCLUSION Urgent thrombolysis followed by elective PCI was an appropriate strategy for the management of simultaneous CCI.展开更多
Acute mountain sickness(AMS) is an illness caused by hypoxia due to rapid ascent to altitudes above 2,500 m. Symptoms include headache,nausea, vomiting, and loss of appetite, all of which usually improve within 1 to 2...Acute mountain sickness(AMS) is an illness caused by hypoxia due to rapid ascent to altitudes above 2,500 m. Symptoms include headache,nausea, vomiting, and loss of appetite, all of which usually improve within 1 to 2 days. However,untreated AMS can progress to life-threatening conditions such as high-altitude cerebral and pulmonary edema(HACE and HAPE, respectively)^([1]).展开更多
BACKGROUND Acute appendicitis(AAp)is a prevalent medical condition characterized by inflammation of the appendix that frequently necessitates urgent surgical procedures.Approximately two-thirds of patients with AAp ex...BACKGROUND Acute appendicitis(AAp)is a prevalent medical condition characterized by inflammation of the appendix that frequently necessitates urgent surgical procedures.Approximately two-thirds of patients with AAp exhibit characteristic signs and symptoms;hence,negative AAp and complicated AAp are the primary concerns in research on AAp.In other terms,further investigations and algorithms are required for at least one third of patients to predict the clinical condition and distinguish them from uncomplicated patients with AAp.AIM To use a Stochastic Gradient Boosting(SGB)-based machine learning(ML)algorithm to tell the difference between AAp patients who are complicated and those who are not,and to find some important biomarkers for both types of AAp by using modeling to get variable importance values.METHODS This study analyzed an open access data set containing 140 people,including 41 healthy controls,65 individuals with uncomplicated AAp,and 34 individuals with complicated AAp.We analyzed some demographic data(age,sex)of the patients and the following biochemical blood parameters:White blood cell(WBC)count,neutrophils,lymphocytes,monocytes,platelet count,neutrophil-tolymphocyte ratio,lymphocyte-to-monocyte ratio,mean platelet volume,neutrophil-to-immature granulocyte ratio,ferritin,total bilirubin,immature granulocyte count,immature granulocyte percent,and neutrophil-to-immature granulocyte ratio.We tested the SGB model using n-fold cross-validation.It was implemented with an 80-20 training-test split.We used variable importance values to identify the variables that were most effective on the target.RESULTS The SGB model demonstrated excellent performance in distinguishing AAp from control patients with an accuracy of 96.3%,a micro aera under the curve(AUC)of 94.7%,a sensitivity of 94.7%,and a specificity of 100%.In distinguishing complicated AAp patients from uncomplicated ones,the model achieved an accuracy of 78.9%,a micro AUC of 79%,a sensitivity of 83.3%,and a specificity of 76.9%.The most useful biomarkers for confirming the AA diagnosis were WBC(100%),neutrophils(95.14%),and the lymphocyte-monocyte ratio(76.05%).On the other hand,the most useful biomarkers for accurate diagnosis of complicated AAp were total bilirubin(100%),WBC(96.90%),and the neutrophil-immature granulocytes ratio(64.05%).CONCLUSION The SGB model achieved high accuracy rates in identifying AAp patients while it showed moderate performance in distinguishing complicated AAp patients from uncomplicated AAp patients.Although the model's accuracy in the classification of complicated AAp is moderate,the high variable importance obtained is clinically significant.We need further prospective validation studies,but the integration of such ML algorithms into clinical practice may improve diagnostic processes.展开更多
BACKGROUND The incidence of acute myocardial infarction(AMI)is rising,with cardiac rupture accounting for approximately 2%of deaths in patients with acute ST-segment elevation myocardial infarction(STEMI).Ventricular ...BACKGROUND The incidence of acute myocardial infarction(AMI)is rising,with cardiac rupture accounting for approximately 2%of deaths in patients with acute ST-segment elevation myocardial infarction(STEMI).Ventricular free wall rupture(FWR)occurs in approximately 2%of AMI patients and is notably rare in patients with non-STEMI.Types of cardiac rupture include left ventricular FWR,ventricular septal rupture,and papillary muscle rupture.The FWR usually leads to acute cardiac tamponade or electromechanical dissociation,where standard resuscitation efforts may not be effective.Ventricular septal rupture and papillary muscle rupture often result in refractory heart failure,with mortality rates over 50%,even with surgical or percutaneous repair options.CASE SUMMARY We present a rare case of an acute non-STEMI patient who suffered sudden FWR causing cardiac tamponade and loss of consciousness immediate before undergoing coronary angiography.Prompt resuscitation and emergency open-heart repair along with coronary artery bypass grafting resulted in successful patient recovery.CONCLUSION This case emphasizes the risks of AMI complications,shares a successful treatment scenario,and discusses measures to prevent such complications.展开更多
Respiratory infections are associated with high morbidity and mortality and are a major global health problem[1].Acute respiratory infections are caused by multiple respiratory pathogens,including viruses and bacteria...Respiratory infections are associated with high morbidity and mortality and are a major global health problem[1].Acute respiratory infections are caused by multiple respiratory pathogens,including viruses and bacteria.Viral-bacterial co-infections,which have become increasingly common and a global concern,can lead to substantial complications,causing higher morbidity and adverse prognosis[2].Previous studies have reported low positive detection rates of targeted pathogens related to acute respiratory infections,owing to the limited number of detected pathogens and variations in the sensitivity of diagnostic methods[3-4].Low positive detection rates may impede our understanding of respiratory pathogen characteristics and hamper the development of precise treatment and prevention strategies.展开更多
BACKGROUND Painless acute pancreatitis(PAP)is a slowly progressive disease that involves inflammation,scarring,and thickening of pancreatic cells,which can happen due to either alcohol,idiopathic,or genetic.Clinicians...BACKGROUND Painless acute pancreatitis(PAP)is a slowly progressive disease that involves inflammation,scarring,and thickening of pancreatic cells,which can happen due to either alcohol,idiopathic,or genetic.Clinicians usually miss PAP due to lack of pain and additional symptoms of hypotension and fever can lead to an infectious work-up instead.In this case report,we discuss the importance of the rapid discovery of this condition to prevent devastating complications like diabetes,necrotizing pancreatitis,or even death.CASE SUMMARY A 47-years old male with past medical history of hypotension and alcohol abuse presented for loss of consciousness.Patient was found with pinpoint pupils,hypoglycemia,and hypotensive.He received Narcan,dextrose,and IV fluids and became responsive.In the emergency department,the patient was hypotensive and the physical exam was only significant for diaphoresis.Patient denied abdominal or radiating pain.Labs significant for elevated lipase,metabolic acidosis,and hyponatremia with imaging positive for AP without chronic inflammation.Based on imaging,lipase and absence of pain,PAP was diagnosed.Patient had multiple episodes of hypoglycemia and remained hypotensive requiring pressor support and intubation.After intubation,he had pulseless electrical activity cardiac arrest.Return of spontaneous circulation achieved but the patient had worsening acidosis,acute kidney injury,liver injury,and bandemia.Empiric antibiotics started,dexamethasone,and maxed on five pressors and transferred to the medical intensive care unit for management of severe AP(SAP).CONCLUSION This case report featured PAP without chronic inflammation which is an even rarer disease than PAP which progressed to SAP.展开更多
Hepatitis A virus(HAV)infection remains a significant public health concern in many developing countries.The annual incidence of HAV infection is 1.5 million,though this figure may be underestimated owing to the infec...Hepatitis A virus(HAV)infection remains a significant public health concern in many developing countries.The annual incidence of HAV infection is 1.5 million,though this figure may be underestimated owing to the infection’s asymptomatic nature and the presence of milder disease variants.The clinical spectrum of HAV infection now ranges from asymptomatic infection to fulminant hepatitis.Despite the availability of safe and highly effective vaccines,HAV infections remain a major contributor to acute viral hepatitis worldwide.展开更多
Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be e...Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.展开更多
基金supported by Hebei Province Natural Science Foundation(H2023423037)The Government Funded Clinical Program of Hebei Province(No.ZF2025287)+1 种基金Special Project of Hebei Industrial Technology Institute for Traditional Chinese Medicine Preparation(No.YJY2024001)Chinese Medicine Scientific Research Program of Hebei Province(No.2025222).
文摘Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually with>20%mortality.Its progression involves metabolic imbalances,toxin accumulation,and multiorgan failure,often culminating in chronic kidney disease.Current therapies(fluid resuscitation,diuretics,renal replacement therapy)remain limited.Inflammation drives AKI pathogenesis:renal insults(ischemia,toxins)trigger tubular cell release of pro-inflammatory mediators(TNF-α,IL-1β,IL-6),activating neutrophil gelatinase-associated lipocalin(NGAL)and dysregulating P38 MAPK/ERK pathways.This cascade promotes leukocyte infiltration,oxidative stress,and apoptosis,exacerbating renal damage.Ononin,a flavonoid from Astragali Radix,shows multi-target potential by suppressing pro-inflammatory cytokines,modulating signaling,and mitigating oxidative stress.Its dual anti-inflammatory/antioxidant properties position it as a promising candidate for AKI intervention.Exploring the ameliorative effect of ononin on the inflammatory response Ameliorative effect of ononin on the inflammatory response in doxorubicin-induced AKI mice.Methods:We used network pharmacology to explore ononin’s target molecules and AKI-related disease molecules,identified their intersections,and predicted potential mechanisms via enrichment analysis,followed by molecular docking verification.For in-vivo validation,50 mice were randomly divided into five groups(n=10/group):Control,Model,Ononin-L(15 mg/kg),Ononin-H(60 mg/kg),and Dexamethasone(2.6 mg/kg).An AKI model was established by intravenous tail-vein injection of Doxorubicin(15 mg/kg).Samples were collected 12 h post-induction.We calculated the renal coefficient,examined renal histopathology using hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson’s trichrome(MASSON)staining,and observed mitochondrial morphology by electron microscopy(EM).ELISA was used to measure NGAL,serum creatinine(Scr),and blood urea nitrogen(BUN)levels in serum.Immunofluorescence(IF)evaluated the expression of P-P38,P-ERK,NGAL,and KIM-1 in renal tissues.RT-qPCR assessed the gene expression of pro-inflammatory cytokines,MAPK pathway components,and renal injury markers in kidney tissues.Western Blot(WB)quantified P-P38,P38 MAPK,P-ERK,ERK,NGAL,and KIM-1 in renal tissues.Results:Network pharmacology analysis suggested that ononin could attenuate AKI through its anti-inflammatory properties and regulation of the MAPK signaling pathway.The Model group exhibited a significantly elevated renal coefficient(P<0.05),severe histopathological damage,and mitochondrial dysfunction compared to controls.Serum levels of NGAL,Scr,and BUN were markedly increased(P<0.05),indicating impaired renal function.Enhanced fluorescence signals of P-P38 MAPK,P-ERK,NGAL,and KIM-1 suggested activation of MAPK pathways and renal injury.Upregulation of pro-inflammatory cytokines(IL-1β,IL-6,TNF-α)and MAPK-related genes(P38 MAPK,ERK)alongside injury markers(NGAL,KIM-1)(P<0.05).Increased ratios of phosphorylated-to-total proteins(P-P38/P38,P-ERK/ERK)and elevated NGAL/KIM-1 protein levels confirmed pathway dysregulation.Treatment significantly reduced the renal coefficient(P<0.05),attenuated histological damage,and restored mitochondrial integrity.NGAL,Scr,and BUN levels were lowered,reflecting functional recovery.Diminished fluorescence intensities of P-P38,P-ERK,NGAL,and KIM-1 indicated suppression of injury pathways.Downregulation of inflammatory cytokines(IL-1β,IL-6,TNF-α),MAPK components(P38 MAPK,ERK),and injury markers(NGAL,KIM-1)(P<0.05).Reduced phosphorylation ratios(P-P38/P38,P-ERK/ERK)and decreased NGAL/KIM-1 protein expression demonstrated therapeutic efficacy.Conclusion:Ononin ameliorates inflammatory responses in AKI mice via the P38 MAPK/ERK pathway.
基金Supported by the Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University,No.CX2023021.
文摘Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)has garnered increasing attention.Compared to AP caused by other causes,HTG-AP often has a more subtle onset but is more likely to progress to a severe,critical illness that poses a serious threat to a patient’s life and health.Research suggests a potential connection between the gut microbiota and AP,which could be mediated by bacterial metabolites,immune cells,and inflammatory factors.This is supported by observations of microbial imbalance and higher intestinal permeability in patients with AP.In addition,studies have shown that HTG-induced changes in gut microbiota can worsen AP by negatively impacting the host metabolism,immune response,and function of the intestinal barrier.In this review,we summarize recent clinical and animal studies on the role and mechanism of gut microbiota in the severity of AP aggravated by HTG.The application prospects of the newly proposed microbial-host-isozyme concept are summarized,focusing on its potential for the precision diagnosis and treatment of HTG-AP through gut microbiota regulation.
基金funded by the National Natural Science Foundation of China(Grant No.82470766 to H.M.)the Jiangsu Provincial Medical Key Discipline(Laboratory)Cultivation Unit(Grant No.JSDW202206 to C.X.)the First Affiliated Hospital of Nanjing Medical University Clinical Capacity Enhancement Project(Grant No.JSPH-MC-2022-18 to C.X.).
文摘Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.
基金supported by the National Natural Science Foundation of China(Grant No.82220108002 to F.C.and Grant No.82273737 to R.Z.)the U.S.National Institutes of Health(Grant Nos.CA209414,HL060710,and ES000002 to D.C.C.,Grant Nos.CA209414 and CA249096 to Y.L.)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)supported by the Qing Lan Project of the Higher Education Institutions of Jiangsu Province and the Outstanding Young Level Academic Leadership Training Program of Nanjing Medical University.
文摘Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.
文摘AIM:To investigate the long-term outcomes in acute primary angle closure(APAC)patients treated with lens extraction(LE)surgery and to identify risk factors for glaucomatous optic neuropathy(GON).METHODS:In this longitudinal observational study,detailed medical histories of APAC patients and comprehensive ophthalmic examinations at final followup were collected.Logistic regression analysis was performed to identify predictors of blindness.Univariate and multivariate linear regression analyses were conducted to determine risk factors associated with visual outcomes.RESULTS:This study included 39 affected eyes of 31 subjects(26 females)with an average age of 74.1±8.0y.At 6.7±4.2y after APAC attack,2(5.7%)eyes had bestcorrected visual acuity(VA)worse than 3/60.Advanced glaucomatous visual field loss was observed in 15(39.5%)affected eyes and 5(25.0%)fellow eyes.Nine affected eyes(23.7%)had GON,and 11(28.9%)were blind.Six(15.4%)affected eyes and 2(9.1%)fellow eyes had suspicious progression.A significantly higher blindness rate in factory workers compared to office workers.Logistic regression identified that worse VA at attack(OR 10.568,95%CI 1.288-86.695;P=0.028)and worse early postoperative VA(OR 13.214,95%CI 1.157-150.881;P=0.038)were risk factors for blindness.Multivariate regression showed that longer duration of elevated intraocular pressure(P=0.004)and worse early postoperative VA(P=0.009)were associated with worse visual outcomes.CONCLUSION:Despite LE surgery,some APAC patients experience continued visual function deterioration.Lifelong monitoring is necessary.Target pressure and progression rates should be re-evaluated during follow-up.
文摘BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.
基金the Scientific and Technological Research Council of Türkiye(TÜBİTAK)Under the International Postdoctoral Research Fellowship Program(2219),No.1059B192400980the National Postdoctoral Research Fellowship Program(2218),No.122C158.
文摘Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.
基金supported by National Natural Science Foundation of China(81272737).
文摘Acute pancreatitis(AP)is a prevalent gastrointestinal disease necessitating hospitalization globally,with an annual incidence ranging from 13 to 45 per 100,000 individuals[1]and a mortality rate of 5%-10%.[2]While most cases follow a self-limiting course,approximately 20%-30%of cases progress to severe acute pancreatitis(SAP),characterized by pancreatic necrosis and multiorgan failure,with the mortality rate increasing to 36%-50%.
基金funded by the Hunan Provincial Natural Science Foundation of China(2024JJ2038,2024JJ9161)the Central Government Guides Local Science and Technology Development Fund Projects(2024ZYC031)+4 种基金the Hunan Health High-Level Talent Project(R2023073)the National Key Clinical Specialty Scientific Research Project(Z2023114)the Young Doctor Foundation of Hunan Provincial People’s Hospital(BSJJ202209)the Key Cultivation Project of Hunan Provincial People’s Hospital(RS2022A06)the Clinical Research Center for Emergency and Critical Care in Hunan Province(2021SK4011).
文摘Acute respiratory distress syndrome(ARDS)is a severe clinical condition characterized by acute respiratory failure due to widespread pulmonary inflammation and edema.The incidence of ARDS among intensive care unit(ICU)patients is approximately 10%,with mortality rates ranging from 35%to 45%and exceeding 50%in severe cases.[1]Identifying and controlling risk factors for ARDS is critical for early prevention.Smoking remains a significant global public health issue,affecting one-third of adults and 40%of children through exposure to secondhand smoke.[2]In an animal study,cigarette smoke impaired lung endothelial barrier function through oxidative stress and exacerbated lipopolysaccharide-induced increases in vascular permeability in vivo.This finding is consistent with the pathological changes observed in ARDS.[3]Although many observational studies have suggested a potential link between smoking and ARDS,the causal relationship remains unclear.This study uses Mendelian randomization(MR)to explore whether smoking behavior causally influences ARDS and investigates the mechanisms by which smoking may contribute to ARDS development through transcriptomic analysis of the Gene Expression Omnibus(GEO)database.
文摘Acute fatty liver of pregnancy(AFLP)is a rare but potentially life-threatening liver disease associated with mitochondrial dysfunction.It is characterized by microvesicular hepatic steatosis and typically occurs in the third trimester,though it may rarely present postpartum.AFLP is considered a non-thrombotic microangiopathy(TMA)but may present with overlapping TMA features.Its incidence ranges from 1 in 7000 to 1 in 20000 pregnancies,although milder cases may go unrecognized.AFLP can rapidly progress to acute liver failure and 20%to 40%of affected women exhibit clinical features of preeclampsia.Acute kidney injury(AKI)is a frequent complication,observed in 55%to 75%of AFLP cases,which is significantly higher than the 7%to 20%occurrence seen in preeclampsia or hemolysis,elevated liver enzymes,and low platelets syndrome.The exact mechanism behind AKI in AFLP remains unclear,but renal histology has shown tubular deposits of free fatty acids,which correlate with current theories regarding liver pathology.While AFLP-associated AKI is often reversible after delivery,some patients may develop persistent AKI that requires dialysis.Therapeutic plasma exchange(TPE)has been explored in these cases,but available evidence is limited.This review summarizes the current understanding of the epidemiology,pathophysiology,clinical features,and management of AKI in the context of AFLP,and discusses the potential role of adjunctive therapies such as TPE.
文摘BACKGROUND Acute disseminated encephalomyelitis(ADEM),which is rare,primarily affects children.It usually manifests as acute encephalopathy and multifocal neurological impairments after infection or vaccination.Diagnosis is still difficult due to the clinical and radiological similarity to other central nervous system disorders.Adult-onset ADEM calls for thorough reporting in order to improve diagnosis and treatment.CASE SUMMARY A 55-year-old man with hypertension had a high fever,intense headache and a steady decline in his neurological function after two weeks.Left facial paralysis was the initial symptom,which progressed to left hemiparesis,reduced consciousness level,photophobia,phonophobia,vomiting,and a focal seizure in the right leg.He had no history of autoimmune disease,vaccinations,or infections.Investigations showed negative infectious/autoimmune serology,mild cerebrospinal fluid lymphocytic pleocytosis(protein 76 mg/dL),and lymphopenia.Brain magnetic resonance imaging without contrast revealed bilateral,symmetrical T2/fluid-attenuated inversion recovery hyperintensities,primarily in the middle cerebellar peduncles,with minor involvement in the pontine and periventricular regions.Neoplastic,metabolic,vascular,and infectious conditions were not included.The patient showed spontaneous neurological improvement by Week 3 with near-complete motor recovery(limb strength 4/5)after methylprednisolone and rehabilitation,despite logistical delays in starting immunotherapy.The monophasic course and radiological/clinical remission were supported by idiopathic ADEM.CONCLUSION This case shows an uncommon,idiopathic,cerebellar-predominant ADEM variation in an adult without conventional triggers.It emphasizes the diagnostic difficulty in distinguishing ADEM from mimics(such as stroke or infection)in adults.Spontaneous improvement before treatment,although early detection is still crucial,should be highlighted,although early detection is still crucial.Increased clinician awareness,fair access to neuroimaging,and focused research on adult ADEM are crucial to fill these gaps and improve outcomes in places with limited resources.
文摘BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HAV,as evident by cases of acute hepatitis due to HAV among adults.AIM To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus(HEV)infection.METHODS This was a trend analysis conducted at Aga Khan University Hospital Karachi(Sindh,Pakistan)from February 2024 to May 2024.Individuals aged 18 years and older diagnosed with acute viral hepatitis attributed to hepatotropic viruses in 2024 were reviewed.To compare the trend patients admitted with acute hepatitis during 2019-2023 were also reviewed.Data regarding clinical and laboratory parameters were recorded.The yearly trend of acute hepatitis due to HAV and HEV was analyzed,and comparative analysis was done between HAV and HEV cases among adults.RESULTS A total of 396 patients were found to have acute hepatitis during our study duration.HAV was diagnosed in 234 patients(59%)while 157 patients(39.6%)were found to have acute HEV infection.Additionally,acute hepatitis B virus infection was identified in 3 patients(0.7%),whereas acute hepatitis C virus infection was found in 2(0.5%)cases of acute hepatitis.Yearly trends showed increasing occurrence of HAV infection among adults over last 5 years.The patients with acute HAV were younger than patients with HEV(28 years±8 years vs 30 years±8 years;P<0.01).Higher levels of total bilirubin were seen in HEV infection,while higher levels of alanine transaminase were seen in HAV infection.However,a higher proportion of acute liver failure(ALF),coagulopathy,and mortality were observed in HEV.CONCLUSION An increase in acute hepatitis A cases among adults shows less severity than hepatitis E,highlighting the need for better sanitation,hygiene,and adult hepatitis A vaccination programs.
文摘BACKGROUND Simultaneous acute ischemic stroke(AIS)and myocardial infarction(cardio-cerebral ischemic attack)have rarely been reported in the literature.Currently,no clear evidence-based guidelines or clinical trials exist to determine the optimal therapeutic strategy for these patients.CASE SUMMARY We present the case of a 27-year-old Chinese man who simultaneously experie-nced acute concomitant cerebrocardiac infarction(CCI)and painless ST-elevation myocardial infarction.The patient was successfully treated with elective percu-taneous coronary intervention(PCI)after receiving urgent systemic thrombolysis at the standard dose for AIS.CONCLUSION Urgent thrombolysis followed by elective PCI was an appropriate strategy for the management of simultaneous CCI.
文摘Acute mountain sickness(AMS) is an illness caused by hypoxia due to rapid ascent to altitudes above 2,500 m. Symptoms include headache,nausea, vomiting, and loss of appetite, all of which usually improve within 1 to 2 days. However,untreated AMS can progress to life-threatening conditions such as high-altitude cerebral and pulmonary edema(HACE and HAPE, respectively)^([1]).
文摘BACKGROUND Acute appendicitis(AAp)is a prevalent medical condition characterized by inflammation of the appendix that frequently necessitates urgent surgical procedures.Approximately two-thirds of patients with AAp exhibit characteristic signs and symptoms;hence,negative AAp and complicated AAp are the primary concerns in research on AAp.In other terms,further investigations and algorithms are required for at least one third of patients to predict the clinical condition and distinguish them from uncomplicated patients with AAp.AIM To use a Stochastic Gradient Boosting(SGB)-based machine learning(ML)algorithm to tell the difference between AAp patients who are complicated and those who are not,and to find some important biomarkers for both types of AAp by using modeling to get variable importance values.METHODS This study analyzed an open access data set containing 140 people,including 41 healthy controls,65 individuals with uncomplicated AAp,and 34 individuals with complicated AAp.We analyzed some demographic data(age,sex)of the patients and the following biochemical blood parameters:White blood cell(WBC)count,neutrophils,lymphocytes,monocytes,platelet count,neutrophil-tolymphocyte ratio,lymphocyte-to-monocyte ratio,mean platelet volume,neutrophil-to-immature granulocyte ratio,ferritin,total bilirubin,immature granulocyte count,immature granulocyte percent,and neutrophil-to-immature granulocyte ratio.We tested the SGB model using n-fold cross-validation.It was implemented with an 80-20 training-test split.We used variable importance values to identify the variables that were most effective on the target.RESULTS The SGB model demonstrated excellent performance in distinguishing AAp from control patients with an accuracy of 96.3%,a micro aera under the curve(AUC)of 94.7%,a sensitivity of 94.7%,and a specificity of 100%.In distinguishing complicated AAp patients from uncomplicated ones,the model achieved an accuracy of 78.9%,a micro AUC of 79%,a sensitivity of 83.3%,and a specificity of 76.9%.The most useful biomarkers for confirming the AA diagnosis were WBC(100%),neutrophils(95.14%),and the lymphocyte-monocyte ratio(76.05%).On the other hand,the most useful biomarkers for accurate diagnosis of complicated AAp were total bilirubin(100%),WBC(96.90%),and the neutrophil-immature granulocytes ratio(64.05%).CONCLUSION The SGB model achieved high accuracy rates in identifying AAp patients while it showed moderate performance in distinguishing complicated AAp patients from uncomplicated AAp patients.Although the model's accuracy in the classification of complicated AAp is moderate,the high variable importance obtained is clinically significant.We need further prospective validation studies,but the integration of such ML algorithms into clinical practice may improve diagnostic processes.
文摘BACKGROUND The incidence of acute myocardial infarction(AMI)is rising,with cardiac rupture accounting for approximately 2%of deaths in patients with acute ST-segment elevation myocardial infarction(STEMI).Ventricular free wall rupture(FWR)occurs in approximately 2%of AMI patients and is notably rare in patients with non-STEMI.Types of cardiac rupture include left ventricular FWR,ventricular septal rupture,and papillary muscle rupture.The FWR usually leads to acute cardiac tamponade or electromechanical dissociation,where standard resuscitation efforts may not be effective.Ventricular septal rupture and papillary muscle rupture often result in refractory heart failure,with mortality rates over 50%,even with surgical or percutaneous repair options.CASE SUMMARY We present a rare case of an acute non-STEMI patient who suffered sudden FWR causing cardiac tamponade and loss of consciousness immediate before undergoing coronary angiography.Prompt resuscitation and emergency open-heart repair along with coronary artery bypass grafting resulted in successful patient recovery.CONCLUSION This case emphasizes the risks of AMI complications,shares a successful treatment scenario,and discusses measures to prevent such complications.
基金supported by the Beijing Science and Technology Planning Project of the Beijing Science and Technology Commission(Z241100009024047)the High-Level Public Health Technical Talent Training Plan(lingjunrencai-01-02).
文摘Respiratory infections are associated with high morbidity and mortality and are a major global health problem[1].Acute respiratory infections are caused by multiple respiratory pathogens,including viruses and bacteria.Viral-bacterial co-infections,which have become increasingly common and a global concern,can lead to substantial complications,causing higher morbidity and adverse prognosis[2].Previous studies have reported low positive detection rates of targeted pathogens related to acute respiratory infections,owing to the limited number of detected pathogens and variations in the sensitivity of diagnostic methods[3-4].Low positive detection rates may impede our understanding of respiratory pathogen characteristics and hamper the development of precise treatment and prevention strategies.
文摘BACKGROUND Painless acute pancreatitis(PAP)is a slowly progressive disease that involves inflammation,scarring,and thickening of pancreatic cells,which can happen due to either alcohol,idiopathic,or genetic.Clinicians usually miss PAP due to lack of pain and additional symptoms of hypotension and fever can lead to an infectious work-up instead.In this case report,we discuss the importance of the rapid discovery of this condition to prevent devastating complications like diabetes,necrotizing pancreatitis,or even death.CASE SUMMARY A 47-years old male with past medical history of hypotension and alcohol abuse presented for loss of consciousness.Patient was found with pinpoint pupils,hypoglycemia,and hypotensive.He received Narcan,dextrose,and IV fluids and became responsive.In the emergency department,the patient was hypotensive and the physical exam was only significant for diaphoresis.Patient denied abdominal or radiating pain.Labs significant for elevated lipase,metabolic acidosis,and hyponatremia with imaging positive for AP without chronic inflammation.Based on imaging,lipase and absence of pain,PAP was diagnosed.Patient had multiple episodes of hypoglycemia and remained hypotensive requiring pressor support and intubation.After intubation,he had pulseless electrical activity cardiac arrest.Return of spontaneous circulation achieved but the patient had worsening acidosis,acute kidney injury,liver injury,and bandemia.Empiric antibiotics started,dexamethasone,and maxed on five pressors and transferred to the medical intensive care unit for management of severe AP(SAP).CONCLUSION This case report featured PAP without chronic inflammation which is an even rarer disease than PAP which progressed to SAP.
文摘Hepatitis A virus(HAV)infection remains a significant public health concern in many developing countries.The annual incidence of HAV infection is 1.5 million,though this figure may be underestimated owing to the infection’s asymptomatic nature and the presence of milder disease variants.The clinical spectrum of HAV infection now ranges from asymptomatic infection to fulminant hepatitis.Despite the availability of safe and highly effective vaccines,HAV infections remain a major contributor to acute viral hepatitis worldwide.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82260812 and 81803838)the Guizhou Provincial Science&Technology Program,China(Project Nos.:YQK[2023]038 and[2020]5007)+1 种基金the Beijing Natural Science Foundation,China(Grant No.:7254489)the Science and Technology Program of Zunyi city of Guizhou province of China(Project Nos.:(2022)420,[2021]-3,[2020]7,and(2022)419).
文摘Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.