Cardiac arrest(CA)is considered a state of clinical death in which the heart suddenly loses its ability to effectively expel blood,resulting in circulatory and respiratory arrest.CA is often catastrophic for patients,...Cardiac arrest(CA)is considered a state of clinical death in which the heart suddenly loses its ability to effectively expel blood,resulting in circulatory and respiratory arrest.CA is often catastrophic for patients,as it can cause serious long-term cardiovascular and cerebrovascular complications that affect their quality of life[1].Survey data indicate that the overall incidence rate of intraoperative CA in patients undergoing thoracic surgery in China is currently 0.138%[2].This rate is expected to increase because of the increasing proportion of older individuals(age>60 years)in the population,as well as the increasing pulmonary surgery rates.However,the incidence rate during the perianesthetic period in older patients undergoing thoracic surgery has not yet been comprehensively reported.展开更多
Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the inju...Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the injury and pathophysiological mechanisms underlying PCAS remain unclear.Experimental animal models are valuable tools for exploring the etiology,pathogenesis,and potential interventions for CA and PCAS.Current CA animal models include electrical induction of ventricular fibrillation(VF),myocardial infarction,high potassium,asphyxia,and hemorrhagic shock.Although these models do not fully replicate the complexity of clinical CA,the mechanistic insights they provide remain highly relevant,including post-CA brain injury(PCABI),post-CA myocardial dysfunction(PAMD),systemic ischaemia/reperfusion injury(IRI),and the persistent precipitating pathology.Summarizing the methods of establishing CA models,the challenges encountered in the modeling process,and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.展开更多
BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is ...BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is essential for improving post-resuscitation survival.This study investigated the mechanisms and common targets of myocardial dysfunction and brain injury after resuscitation.METHODS:The male Sprague-Dawley rats(10–12 weeks old,400–500 g) were divided into two groups:the control group(n=6),which received sham surgery,and the CA/CPR group(n=10),which received ventricular fibrillation(VF) followed by CPR.After 24 h,brain and heart tissues were collected for analysis.The sequencing was used to identify differentially expressed genes(DEGs) between control and CA/CPR rats.RESULTS:At 24 h after resuscitation,CA/CPR rats presented 217 DEGs in the hippocampus and 80 DEGs in the left ventricle(LV) compared to the control group.In the hippocampus,the most notable biological process was the positive regulation of tumor necrosis factor production,with key pathways related to inflammation and the immune response.In the LV,the Gene Ontology(GO)enrichment analysis revealed that gene alterations were primarily associated with amyloid-beta clearance,a pathway that was also relevant in the brain.Eleven common targets were identified in the DEGs of both heart and brain tissues.The reverse transcription-polymerase chain reaction(RTPCR) validation revealed significant differences in the mRNA expression of Timp1,Apln,Ccl7,and Lgals3 in both LV and hippocampus.CONCLUSION:This study identified possible key genes and underlying mechanisms involved in PCAS.The differential genes Timp1,Apln,Ccl7,and Lgals3 might serve as common biomarkers for myocardial and neurological injury following resuscitation.展开更多
Modern cardiopulmonary resuscitation(CPR)has been established for more than 60 years;however,its success rate remains low.Currently,the global incidence of out-of-hospital cardiac arrest(OHCA)is rising,ranging from 52...Modern cardiopulmonary resuscitation(CPR)has been established for more than 60 years;however,its success rate remains low.Currently,the global incidence of out-of-hospital cardiac arrest(OHCA)is rising,ranging from 52.5 to 97.1 per 100,000 population.[1,2]Survival-to-discharge rates for OHCA and in-hospital cardiac arrest(IHCA)are not satisfactory,with ranges of 1.2%-9.9%and 9.1%-19.1%,respectively.展开更多
Acute myocardial infarction(AMI)is characterized by myocardial necrosis resulting from acute coronary circulatory insufficiency.In cases progressing to cardiac arrest,two interventions are important:sustained high-qua...Acute myocardial infarction(AMI)is characterized by myocardial necrosis resulting from acute coronary circulatory insufficiency.In cases progressing to cardiac arrest,two interventions are important:sustained high-quality cardiopulmonary resuscitation(CPR)and prompt coronary reperfusion to minimize irreversible myocardial damage.With advances in emergency medical care,both emergency thrombolysis and extracorporeal cardiopulmonary resuscitation(ECPR)are utilized,even in prehospital treatment,thereby extending the golden window for rescuing such patients.展开更多
Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to impr...Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has ...Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.展开更多
BACKGROUND Cardiac arrest caused by acute pulmonary embolism(PE)is the most serious clinical circumstance,necessitating rapid identification,immediate cardiopulmonary resuscitation(CPR),and systemic thrombolytic thera...BACKGROUND Cardiac arrest caused by acute pulmonary embolism(PE)is the most serious clinical circumstance,necessitating rapid identification,immediate cardiopulmonary resuscitation(CPR),and systemic thrombolytic therapy.Extracorporeal CPR(ECPR)is typically employed as a rescue therapy for selected patients when conventional CPR is failing in settings where it can be implemented.CASE SUMMARY We present a case of a 69-year-old male who experienced a prolonged cardiac arrest in an ambulance with pulseless electrical activity.Upon arrival at the emergency department with ongoing manual chest compressions,bedside pointof-care ultrasound revealed an enlarged right ventricle without contractility.Acute PE was suspected as the cause of cardiac arrest,and intravenous thrombolytic therapy with 50 mg tissue plasminogen activator was administered during mechanical chest compressions.Despite 31 minutes of CPR,return of spontaneous circulation was not achieved until 8 minutes after initiation of Veno-arterial extracorporeal membrane oxygenation(ECMO)support.Under ECMO support,the hemodynamic status and myocardial contractility significantly improved.However,the patient ultimately did not survive due to intracerebral hemorrhagic complications,leading to death a few days later in the hospital.CONCLUSION This case illustrates the potential of combining systemic thrombolysis with ECPR for refractory cardiac arrest caused by acute PE,but it also highlights the increased risk of significant bleeding complications,including fatal intracranial hemorrhage.展开更多
Unheralded cardiac arrest among previously healthy young people without antecedent illness,months or years after coronavirus disease 2019(COVID-19)vaccination,highlights the urgent need for risk stratification.The mos...Unheralded cardiac arrest among previously healthy young people without antecedent illness,months or years after coronavirus disease 2019(COVID-19)vaccination,highlights the urgent need for risk stratification.The most likely underlying pathophysiology is subclinical myopericarditis and reentrant ventri-cular tachycardia or spontaneous ventricular fibrillation that is commonly preci-pitated after a surge in catecholamines during exercise or the waking hours of terminal sleep.Small patches of inflammation and/or edema can be missed on cardiac imaging and autopsy,and the heart can appear grossly normal.This paper reviews evidence linking COVID-19 vaccines to cardiac arrest where unfortu-nately the majority of victims have had no antecedent clinical evaluation.We propose a comprehensive strategy for evaluating cardiovascular risk post-vaccination,incorporating detailed patient history,antibody testing,and cardiac diagnostics in the best attempt to detect abnormalities before sudden cardiac death.This approach aims to identify individuals at higher risk of cardiac events after COVID-19 vaccination and guide appropriate clinical management.It is prudent for each primary care physician to have a pre-established plan when addressing this issue in their practice.展开更多
BACKGROUND In recent years,the utilization of telemedicine in emergency situations,particularly in the context of cardiac arrest,has garnered increasing attention.This study addresses the comparative effectiveness of ...BACKGROUND In recent years,the utilization of telemedicine in emergency situations,particularly in the context of cardiac arrest,has garnered increasing attention.This study addresses the comparative effectiveness of video-instructed dispatcherassisted cardiopulmonary resuscitation(DA-CPR)vs audio-instructed DA-CPR,offering valuable insights into the evolving landscape of emergency medical guidance through telecommunication methods.AIM To compare the effectiveness of video-instructed DA-CPR and audio-instructed DA-CPR in terms of survival rates to hospital discharge.METHODS We conducted a comprehensive search of electronic databases,including Pub-Med,from inception to October 2023,using keywords such as cardiopulmonary resuscitation(CPR),cardiac arrest,and telemedicine combined with Boolean operators.Language was restricted to English,with no date of publication restrictions.We included studies assessing the impact of DA-CPR guidance through video or audio instruction on the quality of CPR performed by bystanders in reallife and simulated environments.RESULTS Our research strategy yielded 537 references.After the final analysis,we selected 27 articles from the PubMed database that met our inclusion criteria.The mean age of the included participants was 37.1 years.The study presents compelling evidence in favor of video-instructed DA-CPR,showing a significant improvement in survival rates to discharge compared to audio-instructed DA-CPR.CONCLUSION DA-CPR plays a crucial role in the chain of survival for out-of-hospital cardiac arrest patients.Extensive research has consistently demonstrated its effectiveness in increasing bystander-initiated CPR and improving patient outcomes.Ongoing technological advancements,such as video calls and automated external defibrillator integration,continue to refine and enhance the delivery of DA-CPR.However,continuous efforts are required to standardize dispatcher training and further optimize communication strategies to ensure the highest quality of care for cardiac arrest victims.展开更多
BACKGROUND: Targeted temperature management(TTM) is a common therapeutic intervention, yet its cost-effectiveness remains uncertain. This study aimed to evaluate the real-world cost-effectiveness of TTM compared with ...BACKGROUND: Targeted temperature management(TTM) is a common therapeutic intervention, yet its cost-effectiveness remains uncertain. This study aimed to evaluate the real-world cost-effectiveness of TTM compared with that of conventional care in adult out-of-hospital cardiac arrest(OHCA) survivors using clinical patient-level data.METHODS: We conducted a retrospective cohort study at an academic medical center in the USA to assess the cost-effectiveness of TTM in adult non-traumatic OHCA survivors between 1 January, 2019 and 30 June, 2023. The primary outcome was survival to hospital discharge. Incremental cost-effectiveness ratios(ICERs) were calculated and compared with various decision makers' willingness to pay. Cost-effectiveness acceptability curves were utilized to evaluate the economic attractiveness of TTM. Uncertainty about the incremental cost and effect was explored with a 95% confidence ellipse.RESULTS: Among 925 non-traumatic OHCA survivors, only 30(3%) received TTM. After adjusting for potential confounders, the TTM group did not demonstrate a significantly lower cost(delta cost-$5,141, 95% confidence interval [95% CI]: $-35,347 to $25,065, P=0.79) and higher survival to hospital discharge(delta effect 6%, 95% CI:-11% to 23%, P=0.41). Additionally, a 95% confidence ellipse indicated uncertainty reflected by evidence that the true value of the ICER could be in any of the quadrants of the cost-effectiveness plane.CONCLUSION: Although TTM did not demonstrate a clear survival benefit in this study, its potential cost-effectiveness warrants further investigation with larger sample sizes. These findings highlight the need for additional research to optimize TTM use in OHCA care and inform resource allocation decisions.展开更多
The incidence of in-hospital cardiac arrest (IHCA) has increased over the past decade,with more than half occurring in intensive care units (ICUs).^([1])ICU cardiac arrest (ICU-CA)presents unique challenges,with worse...The incidence of in-hospital cardiac arrest (IHCA) has increased over the past decade,with more than half occurring in intensive care units (ICUs).^([1])ICU cardiac arrest (ICU-CA)presents unique challenges,with worse outcomes than those in monitored wards,highlighting the need for early detection and intervention.^([2])Up to 80%of patients exhibit signs of deterioration hours before IHCA.^([3])Although early warning scores based on vital signs are useful,their eff ectiveness in ICUs is limited due to abnormal physiological parameters.^([4])Laboratory markers,such as sodium,potassium,and lactate,are predictive of poor outcomes,^([5])but static measurements may not capture the patient’s trajectory.Trends in laboratory indicators,such as variability and extremes,may offer better predictive value.^([6])This study aimed to evaluate ICU-CA predictive factors,with a focus on vital signs and trends of laboratory indicators.展开更多
Cardiac arrest(CA)is a major global public health challenge,and its high morbidity and low survival rate pose severe tests for emergency and critical care.Although modern CPR techniques significantly improve the immed...Cardiac arrest(CA)is a major global public health challenge,and its high morbidity and low survival rate pose severe tests for emergency and critical care.Although modern CPR techniques significantly improve the immediate resuscitation success rate in CA patients,poor outcomes such as neurological impairment still significantly increase the long-term care burden and reduce the quality of survival.In recent years,the application of remote ischemic conditioning(RIC)has attracted much attention in the field of cardiac arrest through its unique myocardial-nerve dual protection mechanism against the heart.This paper summarizes the conceptual connotation,physiological mechanism,operation method,and its application progress in CA and explores the potential of this technology in the field of CA care in order to provide reference for the research and application of RIC in the field of emergency care.展开更多
The estimated annual incidence of out-of-hospital cardiac arrest(OHCA)is approximately 120 cases per 100000 inhabitants in western countries.Although the rates of bystander cardiopulmonary resuscitation(CPR)and use of...The estimated annual incidence of out-of-hospital cardiac arrest(OHCA)is approximately 120 cases per 100000 inhabitants in western countries.Although the rates of bystander cardiopulmonary resuscitation(CPR)and use of automated external defibrillator are increasing,the likelihood of survival to hospital discharge is no more than 8%.To date,various devices and methods have been utilized in the initial CPR approach targeting to improve survival and neurological outcomes in OHCA patients.The aim of this review is to discuss strategies that facilitate resuscitation,increase the chance to achieve return to spontaneous circulation and improve survival to hospital discharge and neurological outcomes in the prehospital setting.展开更多
BACKGROUND:This study aims to explore the causal relationship of body weight,body mass index(BMI),and waist circumference (WC) with the risk of cardiac arrest (CA) using two-sample Mendelian randomization (MR).METHODS...BACKGROUND:This study aims to explore the causal relationship of body weight,body mass index(BMI),and waist circumference (WC) with the risk of cardiac arrest (CA) using two-sample Mendelian randomization (MR).METHODS:Data were summarized using genome-wide association studies (GWAS).Twosample MR analyses were performed using the inverse variance weighting (IVW) method,the weighted median method,and the MR-Egger analysis.Heterogeneity test and sensitivity analysis were performed using Cochran’s Q test and the leave-one-out method,respectively.The Steiger test was used to detect reverse causality.Bayesian model-averaged MR was used to identify the most influential risk factors.RESULTS:A total of 13 GWAS data were collected for BMI,body weight and WC.IVW analyses showed a positive correlation of body weight,BMI,and WC with CA (all OR>1 and P<0.05),with MR-Egger and weighted median methods confirming the IVW findings.No horizontal pleiotropy or heterogeneity was observed.Sensitivity analysis indicated that no single nucleotide polymorphism(SNP) caused significant changes in overall causality.Bayesian model-averaged MR was also used to rank causality based on marginal inclusion probability (MIP),and the corresponding modelaveraged causal estimate (MACE) were confirmed,which indicated that WC (GWAS ID:ukb-b-9405)was the highest-ranked risk factor (MIP=0.119,MACE=0.011);its posterior probability was 0.057.A total of 14 sex-specific GWAS data on weight,BMI,and WC were analyzed in relationship with CA,and the MR results showed no significant effects of sex-specific factors.CONCLUSION:Body weight,BMI,and WC are causally associated with an increased risk of CA,with WC identified as the most important risk factor.展开更多
Objectives:Weaning induces oxidative stress in pigs,increasing the risk of diarrhea and death.Intestinal damage is associated with obstructed intestinal cell cycles.To stop damage caused by reactive oxygen species(ROS...Objectives:Weaning induces oxidative stress in pigs,increasing the risk of diarrhea and death.Intestinal damage is associated with obstructed intestinal cell cycles.To stop damage caused by reactive oxygen species(ROS),N-acetyl cysteine(NAC)has been widely employed.In this study,we examined changes in the intestinal cyclin of weaning piglets and assessed the impact of NAC on intestinal cell cycle arrest and intracellular signaling pathways.Methods:We conducted two animal experiments.In the first,we divided 12 litters of 120 newborn piglets into two groups:a control group and a weaning group.The control piglets were allowed to suckle normally.The weaning group was weaned after 3 weeks and fed a normal diet for piglets.We slaughtered six piglets from the control group and six from the weaning group.We observed cyclin changes and intestinal development at days 0,1,4,and 7 after weaning.In the second experiment,we divided 15 litters of 150 piglets that were 2 weeks old into three groups:the control group,the weaning group,and the NAC group.Control piglets were allowed to suckle normally.Piglets in the weaning and NAC groups were weaned when they were 21 days old.The NAC group was fed a basal diet supplemented with 500 mg/kg NAC,and the weaning group was fed the basal diet alone.The experimental period was 14–25 days of age.Four days after weaning,we slaughtered one piglet from each litter.We then analyzed intestinal cell cycle indexes,intestinal oxidative stress,c-Jun N-terminal kinase(JNK),extracellular signal-regulated kinase(ERK),and p38 phosphorylation.Results:Weaning decreased the piglets’feed intake and daily gain,reduced the serum antioxidant capacity,and increased the intestinal ROS level.Furthermore,the jejunum histology and barrier development of the jejunum exhibited damage after weaning,the microvilli displayed hypoplasia,and the p21 and p27 protein expression levels of the jejunum were significantly elevated.We did not observe any significant differences in cyclin D and E after days 1,4,and 7 post-weaning compared with the control group.We observed,however,significantly increased cyclin D and E expression,lower ERK,JNK,and p38 kinase phosphorylation;villus atrophy alleviation;decreased p21 and p27 expression;and increased average daily intake of feed and weight gain.Conclusion:This research demonstrates that weaning stress inhibits piglet intestinal proliferation by reducing cyclin D and cyclin E expression.NAC downregulates p21 and p27 through modulating mitogen-activated protein kinases(MAPKase)phosphorylation,thereby promoting cell proliferation.The results indicate that NAC promotes intestinal function and the integrity of enterocytes and holds promise as a new feed additive for animal health.展开更多
Nonobstructive azoospermia(NOA),one of the most severe types of male infertility,etiology often remains unclear in most cases.Therefore,this study aimed to detect four biallelic detrimental variants(0.5%)in the minich...Nonobstructive azoospermia(NOA),one of the most severe types of male infertility,etiology often remains unclear in most cases.Therefore,this study aimed to detect four biallelic detrimental variants(0.5%)in the minichromosome maintenance domain containing 2(MCMDC2)genes in 768 NOA patients by whole-exome sequencing(WES).Hematoxylin and eosin(H&E)demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients(c.1360G>T,c.1956G>T,and c.685C>T)and hypospermatogenesis in one patient(c.94G>T),as further confirmed through immunofluorescence(IF)staining.The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis.The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses.The results revealed four MCMDC2 variants related to NOA,which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.展开更多
BACKGROUND:Post-cardiac arrest brain injury remains the leading cause of mortality and longterm disability in patients following cardiac arrest(CA).However,optimizing clinical management strategies for bundled therapy...BACKGROUND:Post-cardiac arrest brain injury remains the leading cause of mortality and longterm disability in patients following cardiac arrest(CA).However,optimizing clinical management strategies for bundled therapy after CA still faces challenges.METHODS:For this literature review,we searched PubMed,Web of Science,and SpringerLink databases for high-quality studies published between December 1982 and July 1,2024.The search included randomized clinical trials,meta-analyses,systematic reviews,and observational studies.References in included studies were also checked to identify additional sources.RESULTS:Many studies have identified potential targets for interventions to mitigate brain injury and improve outcomes for post-resuscitated patients.To optimize clinical management strategies to minimize brain injury after CA,we developed the acronym “SOOTEST-ICU” bundle,which includes “SOOTEST” therapy to optimize peripheral oxygen delivery and “ICU” intervention to optimize the cerebral oxygen cascade.The order of the “SOOTEST” treatment was organized based on the severity and importance of brain oxygen aff ecting brain injury.It includes systolic blood pressure and mean arterial pressure management,oxygenation and ventilation management,original etiological treatment,temperature control,electrolytes and acid basic status,seizure control,and targeted substrate delivery.The acronym “ICU” intervention includes intracerebral oxygen delivery,cerebral oxygen diff usion,and oxygen utilization.CONCLUSION:The “SOOTEST-ICU” therapy is developed to optimize oxygen and substrate cascades to minimize brain injury after CA.展开更多
BACKGROUND Cardiac magnetic resonance(CMR)has been reported to identify myocardial damage inducing out-of-hospital cardiac arrest(OHCA).However,the usefulness of CMR may be affected by the medical institutions,patient...BACKGROUND Cardiac magnetic resonance(CMR)has been reported to identify myocardial damage inducing out-of-hospital cardiac arrest(OHCA).However,the usefulness of CMR may be affected by the medical institutions,patients’ages,and myocardial diseases.AIM To clarify the clinical usefulness and limitation of CMR for identifying myocardial damage in the survivors of OHCA in midtown.METHODS Nineteen patients underwent CMR to detect myocardial damage related to OHCA in the midtown of a capital city.Cine,T1 and T2 mapping,T2-weighted,and late gadolinium enhancement(LGE)imaging were acquired using a 1.5 T scanner.We described the clinical characteristics of the survivors of OHCA and evaluated usefulness of CMR for identifying myocardial damage related to OHCA.RESULTS Among 19 patients experiencing OHCA,7 experienced it in trains or on railway platforms,4 while practicing sports,and 4 during their daily work.Ten of the 19 survivors were diagnosed with coronary vasospasm(CVS),in whom CMR failed to depict its characteristic findings.CMR was useful for identifying myocardial damage associated with hypertrophic cardiomyopathy(HCM)or myocardial infarction(MI).LGE was related to serious ventricular arrhythmias after implantable cardioverter defibrillator(ICD)installation in 3 patients(CVS,2;HCM,1).CONCLUSION CMR is useful for identifying myocardial damage of HCM or MI inducing OHCA and predicting ventricular arrhythmias after ICD implantation but has limited capability for detecting myocardial damage of CVS.展开更多
基金supported by the Regional Science Foundation Project of the National Natural Science Foundation of China(Project No:82160157)the Beijing High-Level Public Health Technology Talent Construction Project(Project No.:Leading Talents-03-10).
文摘Cardiac arrest(CA)is considered a state of clinical death in which the heart suddenly loses its ability to effectively expel blood,resulting in circulatory and respiratory arrest.CA is often catastrophic for patients,as it can cause serious long-term cardiovascular and cerebrovascular complications that affect their quality of life[1].Survey data indicate that the overall incidence rate of intraoperative CA in patients undergoing thoracic surgery in China is currently 0.138%[2].This rate is expected to increase because of the increasing proportion of older individuals(age>60 years)in the population,as well as the increasing pulmonary surgery rates.However,the incidence rate during the perianesthetic period in older patients undergoing thoracic surgery has not yet been comprehensively reported.
基金supported by the National Key Research and Development Program(2021YFC3002205)the Postgraduate Research and Innovation Program of Tianjin Municipal Education Commission(2022BKY113),China.
文摘Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the injury and pathophysiological mechanisms underlying PCAS remain unclear.Experimental animal models are valuable tools for exploring the etiology,pathogenesis,and potential interventions for CA and PCAS.Current CA animal models include electrical induction of ventricular fibrillation(VF),myocardial infarction,high potassium,asphyxia,and hemorrhagic shock.Although these models do not fully replicate the complexity of clinical CA,the mechanistic insights they provide remain highly relevant,including post-CA brain injury(PCABI),post-CA myocardial dysfunction(PAMD),systemic ischaemia/reperfusion injury(IRI),and the persistent precipitating pathology.Summarizing the methods of establishing CA models,the challenges encountered in the modeling process,and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
基金supported by the National High Level Hospital Clinical Research Funding (2022-NHLHCRF-YS-03)the National Natural Science Foundation of China (82272196)。
文摘BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is essential for improving post-resuscitation survival.This study investigated the mechanisms and common targets of myocardial dysfunction and brain injury after resuscitation.METHODS:The male Sprague-Dawley rats(10–12 weeks old,400–500 g) were divided into two groups:the control group(n=6),which received sham surgery,and the CA/CPR group(n=10),which received ventricular fibrillation(VF) followed by CPR.After 24 h,brain and heart tissues were collected for analysis.The sequencing was used to identify differentially expressed genes(DEGs) between control and CA/CPR rats.RESULTS:At 24 h after resuscitation,CA/CPR rats presented 217 DEGs in the hippocampus and 80 DEGs in the left ventricle(LV) compared to the control group.In the hippocampus,the most notable biological process was the positive regulation of tumor necrosis factor production,with key pathways related to inflammation and the immune response.In the LV,the Gene Ontology(GO)enrichment analysis revealed that gene alterations were primarily associated with amyloid-beta clearance,a pathway that was also relevant in the brain.Eleven common targets were identified in the DEGs of both heart and brain tissues.The reverse transcription-polymerase chain reaction(RTPCR) validation revealed significant differences in the mRNA expression of Timp1,Apln,Ccl7,and Lgals3 in both LV and hippocampus.CONCLUSION:This study identified possible key genes and underlying mechanisms involved in PCAS.The differential genes Timp1,Apln,Ccl7,and Lgals3 might serve as common biomarkers for myocardial and neurological injury following resuscitation.
文摘Modern cardiopulmonary resuscitation(CPR)has been established for more than 60 years;however,its success rate remains low.Currently,the global incidence of out-of-hospital cardiac arrest(OHCA)is rising,ranging from 52.5 to 97.1 per 100,000 population.[1,2]Survival-to-discharge rates for OHCA and in-hospital cardiac arrest(IHCA)are not satisfactory,with ranges of 1.2%-9.9%and 9.1%-19.1%,respectively.
文摘Acute myocardial infarction(AMI)is characterized by myocardial necrosis resulting from acute coronary circulatory insufficiency.In cases progressing to cardiac arrest,two interventions are important:sustained high-quality cardiopulmonary resuscitation(CPR)and prompt coronary reperfusion to minimize irreversible myocardial damage.With advances in emergency medical care,both emergency thrombolysis and extracorporeal cardiopulmonary resuscitation(ECPR)are utilized,even in prehospital treatment,thereby extending the golden window for rescuing such patients.
基金supported by the Natural Science Fund of Fujian Province,No.2020J011058(to JK)the Project of Fujian Provincial Hospital for High-level Hospital Construction,No.2020HSJJ12(to JK)+1 种基金the Fujian Provincial Finance Department Special Fund,No.(2021)848(to FC)the Fujian Provincial Major Scientific and Technological Special Projects on Health,No.2022ZD01008(to FC).
文摘Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
文摘Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
基金supported by the National Natural Science Foundation of China(32170144 and 32470146).
文摘Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.
基金Supported by Scientific Research Projects from Wuhan Municipal Health Commission of China,No.WX23B42.
文摘BACKGROUND Cardiac arrest caused by acute pulmonary embolism(PE)is the most serious clinical circumstance,necessitating rapid identification,immediate cardiopulmonary resuscitation(CPR),and systemic thrombolytic therapy.Extracorporeal CPR(ECPR)is typically employed as a rescue therapy for selected patients when conventional CPR is failing in settings where it can be implemented.CASE SUMMARY We present a case of a 69-year-old male who experienced a prolonged cardiac arrest in an ambulance with pulseless electrical activity.Upon arrival at the emergency department with ongoing manual chest compressions,bedside pointof-care ultrasound revealed an enlarged right ventricle without contractility.Acute PE was suspected as the cause of cardiac arrest,and intravenous thrombolytic therapy with 50 mg tissue plasminogen activator was administered during mechanical chest compressions.Despite 31 minutes of CPR,return of spontaneous circulation was not achieved until 8 minutes after initiation of Veno-arterial extracorporeal membrane oxygenation(ECMO)support.Under ECMO support,the hemodynamic status and myocardial contractility significantly improved.However,the patient ultimately did not survive due to intracerebral hemorrhagic complications,leading to death a few days later in the hospital.CONCLUSION This case illustrates the potential of combining systemic thrombolysis with ECPR for refractory cardiac arrest caused by acute PE,but it also highlights the increased risk of significant bleeding complications,including fatal intracranial hemorrhage.
文摘Unheralded cardiac arrest among previously healthy young people without antecedent illness,months or years after coronavirus disease 2019(COVID-19)vaccination,highlights the urgent need for risk stratification.The most likely underlying pathophysiology is subclinical myopericarditis and reentrant ventri-cular tachycardia or spontaneous ventricular fibrillation that is commonly preci-pitated after a surge in catecholamines during exercise or the waking hours of terminal sleep.Small patches of inflammation and/or edema can be missed on cardiac imaging and autopsy,and the heart can appear grossly normal.This paper reviews evidence linking COVID-19 vaccines to cardiac arrest where unfortu-nately the majority of victims have had no antecedent clinical evaluation.We propose a comprehensive strategy for evaluating cardiovascular risk post-vaccination,incorporating detailed patient history,antibody testing,and cardiac diagnostics in the best attempt to detect abnormalities before sudden cardiac death.This approach aims to identify individuals at higher risk of cardiac events after COVID-19 vaccination and guide appropriate clinical management.It is prudent for each primary care physician to have a pre-established plan when addressing this issue in their practice.
文摘BACKGROUND In recent years,the utilization of telemedicine in emergency situations,particularly in the context of cardiac arrest,has garnered increasing attention.This study addresses the comparative effectiveness of video-instructed dispatcherassisted cardiopulmonary resuscitation(DA-CPR)vs audio-instructed DA-CPR,offering valuable insights into the evolving landscape of emergency medical guidance through telecommunication methods.AIM To compare the effectiveness of video-instructed DA-CPR and audio-instructed DA-CPR in terms of survival rates to hospital discharge.METHODS We conducted a comprehensive search of electronic databases,including Pub-Med,from inception to October 2023,using keywords such as cardiopulmonary resuscitation(CPR),cardiac arrest,and telemedicine combined with Boolean operators.Language was restricted to English,with no date of publication restrictions.We included studies assessing the impact of DA-CPR guidance through video or audio instruction on the quality of CPR performed by bystanders in reallife and simulated environments.RESULTS Our research strategy yielded 537 references.After the final analysis,we selected 27 articles from the PubMed database that met our inclusion criteria.The mean age of the included participants was 37.1 years.The study presents compelling evidence in favor of video-instructed DA-CPR,showing a significant improvement in survival rates to discharge compared to audio-instructed DA-CPR.CONCLUSION DA-CPR plays a crucial role in the chain of survival for out-of-hospital cardiac arrest patients.Extensive research has consistently demonstrated its effectiveness in increasing bystander-initiated CPR and improving patient outcomes.Ongoing technological advancements,such as video calls and automated external defibrillator integration,continue to refine and enhance the delivery of DA-CPR.However,continuous efforts are required to standardize dispatcher training and further optimize communication strategies to ensure the highest quality of care for cardiac arrest victims.
基金supported by Faculty of MedicineChiang Mai University+2 种基金supported by the National Center for Advancing Translational SciencesNational Institutes of Healththrough grant number UL1 TR001860. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH。
文摘BACKGROUND: Targeted temperature management(TTM) is a common therapeutic intervention, yet its cost-effectiveness remains uncertain. This study aimed to evaluate the real-world cost-effectiveness of TTM compared with that of conventional care in adult out-of-hospital cardiac arrest(OHCA) survivors using clinical patient-level data.METHODS: We conducted a retrospective cohort study at an academic medical center in the USA to assess the cost-effectiveness of TTM in adult non-traumatic OHCA survivors between 1 January, 2019 and 30 June, 2023. The primary outcome was survival to hospital discharge. Incremental cost-effectiveness ratios(ICERs) were calculated and compared with various decision makers' willingness to pay. Cost-effectiveness acceptability curves were utilized to evaluate the economic attractiveness of TTM. Uncertainty about the incremental cost and effect was explored with a 95% confidence ellipse.RESULTS: Among 925 non-traumatic OHCA survivors, only 30(3%) received TTM. After adjusting for potential confounders, the TTM group did not demonstrate a significantly lower cost(delta cost-$5,141, 95% confidence interval [95% CI]: $-35,347 to $25,065, P=0.79) and higher survival to hospital discharge(delta effect 6%, 95% CI:-11% to 23%, P=0.41). Additionally, a 95% confidence ellipse indicated uncertainty reflected by evidence that the true value of the ICER could be in any of the quadrants of the cost-effectiveness plane.CONCLUSION: Although TTM did not demonstrate a clear survival benefit in this study, its potential cost-effectiveness warrants further investigation with larger sample sizes. These findings highlight the need for additional research to optimize TTM use in OHCA care and inform resource allocation decisions.
基金supported by grants from the Key R&D Program of Shandong Province (2021ZLGX02)the National Science Foundation of China (81901934, 82325031)+1 种基金the National Key R&D Program of China (2020YFC1512700, 2020YFC1512705, 2020YFC1512703)the Clinical Research Center of Shandong University (2020SDUCRCC025)。
文摘The incidence of in-hospital cardiac arrest (IHCA) has increased over the past decade,with more than half occurring in intensive care units (ICUs).^([1])ICU cardiac arrest (ICU-CA)presents unique challenges,with worse outcomes than those in monitored wards,highlighting the need for early detection and intervention.^([2])Up to 80%of patients exhibit signs of deterioration hours before IHCA.^([3])Although early warning scores based on vital signs are useful,their eff ectiveness in ICUs is limited due to abnormal physiological parameters.^([4])Laboratory markers,such as sodium,potassium,and lactate,are predictive of poor outcomes,^([5])but static measurements may not capture the patient’s trajectory.Trends in laboratory indicators,such as variability and extremes,may offer better predictive value.^([6])This study aimed to evaluate ICU-CA predictive factors,with a focus on vital signs and trends of laboratory indicators.
文摘Cardiac arrest(CA)is a major global public health challenge,and its high morbidity and low survival rate pose severe tests for emergency and critical care.Although modern CPR techniques significantly improve the immediate resuscitation success rate in CA patients,poor outcomes such as neurological impairment still significantly increase the long-term care burden and reduce the quality of survival.In recent years,the application of remote ischemic conditioning(RIC)has attracted much attention in the field of cardiac arrest through its unique myocardial-nerve dual protection mechanism against the heart.This paper summarizes the conceptual connotation,physiological mechanism,operation method,and its application progress in CA and explores the potential of this technology in the field of CA care in order to provide reference for the research and application of RIC in the field of emergency care.
文摘The estimated annual incidence of out-of-hospital cardiac arrest(OHCA)is approximately 120 cases per 100000 inhabitants in western countries.Although the rates of bystander cardiopulmonary resuscitation(CPR)and use of automated external defibrillator are increasing,the likelihood of survival to hospital discharge is no more than 8%.To date,various devices and methods have been utilized in the initial CPR approach targeting to improve survival and neurological outcomes in OHCA patients.The aim of this review is to discuss strategies that facilitate resuscitation,increase the chance to achieve return to spontaneous circulation and improve survival to hospital discharge and neurological outcomes in the prehospital setting.
基金This study is supported by the National Natural Science Foundation of China (No. 82072127)。
文摘BACKGROUND:This study aims to explore the causal relationship of body weight,body mass index(BMI),and waist circumference (WC) with the risk of cardiac arrest (CA) using two-sample Mendelian randomization (MR).METHODS:Data were summarized using genome-wide association studies (GWAS).Twosample MR analyses were performed using the inverse variance weighting (IVW) method,the weighted median method,and the MR-Egger analysis.Heterogeneity test and sensitivity analysis were performed using Cochran’s Q test and the leave-one-out method,respectively.The Steiger test was used to detect reverse causality.Bayesian model-averaged MR was used to identify the most influential risk factors.RESULTS:A total of 13 GWAS data were collected for BMI,body weight and WC.IVW analyses showed a positive correlation of body weight,BMI,and WC with CA (all OR>1 and P<0.05),with MR-Egger and weighted median methods confirming the IVW findings.No horizontal pleiotropy or heterogeneity was observed.Sensitivity analysis indicated that no single nucleotide polymorphism(SNP) caused significant changes in overall causality.Bayesian model-averaged MR was also used to rank causality based on marginal inclusion probability (MIP),and the corresponding modelaveraged causal estimate (MACE) were confirmed,which indicated that WC (GWAS ID:ukb-b-9405)was the highest-ranked risk factor (MIP=0.119,MACE=0.011);its posterior probability was 0.057.A total of 14 sex-specific GWAS data on weight,BMI,and WC were analyzed in relationship with CA,and the MR results showed no significant effects of sex-specific factors.CONCLUSION:Body weight,BMI,and WC are causally associated with an increased risk of CA,with WC identified as the most important risk factor.
基金supported by the Jilin Agricultural Science and Technology University under the Scientific Startup Foundation for Doctors((2022)733)Shanghai Jiao Tong University under the National Natural Science Foundation of China(30972103).
文摘Objectives:Weaning induces oxidative stress in pigs,increasing the risk of diarrhea and death.Intestinal damage is associated with obstructed intestinal cell cycles.To stop damage caused by reactive oxygen species(ROS),N-acetyl cysteine(NAC)has been widely employed.In this study,we examined changes in the intestinal cyclin of weaning piglets and assessed the impact of NAC on intestinal cell cycle arrest and intracellular signaling pathways.Methods:We conducted two animal experiments.In the first,we divided 12 litters of 120 newborn piglets into two groups:a control group and a weaning group.The control piglets were allowed to suckle normally.The weaning group was weaned after 3 weeks and fed a normal diet for piglets.We slaughtered six piglets from the control group and six from the weaning group.We observed cyclin changes and intestinal development at days 0,1,4,and 7 after weaning.In the second experiment,we divided 15 litters of 150 piglets that were 2 weeks old into three groups:the control group,the weaning group,and the NAC group.Control piglets were allowed to suckle normally.Piglets in the weaning and NAC groups were weaned when they were 21 days old.The NAC group was fed a basal diet supplemented with 500 mg/kg NAC,and the weaning group was fed the basal diet alone.The experimental period was 14–25 days of age.Four days after weaning,we slaughtered one piglet from each litter.We then analyzed intestinal cell cycle indexes,intestinal oxidative stress,c-Jun N-terminal kinase(JNK),extracellular signal-regulated kinase(ERK),and p38 phosphorylation.Results:Weaning decreased the piglets’feed intake and daily gain,reduced the serum antioxidant capacity,and increased the intestinal ROS level.Furthermore,the jejunum histology and barrier development of the jejunum exhibited damage after weaning,the microvilli displayed hypoplasia,and the p21 and p27 protein expression levels of the jejunum were significantly elevated.We did not observe any significant differences in cyclin D and E after days 1,4,and 7 post-weaning compared with the control group.We observed,however,significantly increased cyclin D and E expression,lower ERK,JNK,and p38 kinase phosphorylation;villus atrophy alleviation;decreased p21 and p27 expression;and increased average daily intake of feed and weight gain.Conclusion:This research demonstrates that weaning stress inhibits piglet intestinal proliferation by reducing cyclin D and cyclin E expression.NAC downregulates p21 and p27 through modulating mitogen-activated protein kinases(MAPKase)phosphorylation,thereby promoting cell proliferation.The results indicate that NAC promotes intestinal function and the integrity of enterocytes and holds promise as a new feed additive for animal health.
基金supported by the National Key Research and Development Program of China(2022YFC2702700)the National Natural Science Foundation of China(No.82171586)+1 种基金Inner Mongolia Academy of Medical Sciences Public Hospital Joint Science and Technology Project(2023GLLH0045)Specific Project of Shanghai Jiao Tong University for“Invigorating Inner Mongolia through Science and Technology”(2022XYJG001-01-19).
文摘Nonobstructive azoospermia(NOA),one of the most severe types of male infertility,etiology often remains unclear in most cases.Therefore,this study aimed to detect four biallelic detrimental variants(0.5%)in the minichromosome maintenance domain containing 2(MCMDC2)genes in 768 NOA patients by whole-exome sequencing(WES).Hematoxylin and eosin(H&E)demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients(c.1360G>T,c.1956G>T,and c.685C>T)and hypospermatogenesis in one patient(c.94G>T),as further confirmed through immunofluorescence(IF)staining.The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis.The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses.The results revealed four MCMDC2 variants related to NOA,which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
基金supported by the High-Level Public Health Technical Talent Building Program (Discipline Leader-01-01)Capital’s Funds for Health Improvement and Research (CFH 2022-1-2032)+1 种基金National Natural Science Foundation of China (82072136)Beijing Hospitals Authority’s Ascent Plan (DFL20240302)。
文摘BACKGROUND:Post-cardiac arrest brain injury remains the leading cause of mortality and longterm disability in patients following cardiac arrest(CA).However,optimizing clinical management strategies for bundled therapy after CA still faces challenges.METHODS:For this literature review,we searched PubMed,Web of Science,and SpringerLink databases for high-quality studies published between December 1982 and July 1,2024.The search included randomized clinical trials,meta-analyses,systematic reviews,and observational studies.References in included studies were also checked to identify additional sources.RESULTS:Many studies have identified potential targets for interventions to mitigate brain injury and improve outcomes for post-resuscitated patients.To optimize clinical management strategies to minimize brain injury after CA,we developed the acronym “SOOTEST-ICU” bundle,which includes “SOOTEST” therapy to optimize peripheral oxygen delivery and “ICU” intervention to optimize the cerebral oxygen cascade.The order of the “SOOTEST” treatment was organized based on the severity and importance of brain oxygen aff ecting brain injury.It includes systolic blood pressure and mean arterial pressure management,oxygenation and ventilation management,original etiological treatment,temperature control,electrolytes and acid basic status,seizure control,and targeted substrate delivery.The acronym “ICU” intervention includes intracerebral oxygen delivery,cerebral oxygen diff usion,and oxygen utilization.CONCLUSION:The “SOOTEST-ICU” therapy is developed to optimize oxygen and substrate cascades to minimize brain injury after CA.
文摘BACKGROUND Cardiac magnetic resonance(CMR)has been reported to identify myocardial damage inducing out-of-hospital cardiac arrest(OHCA).However,the usefulness of CMR may be affected by the medical institutions,patients’ages,and myocardial diseases.AIM To clarify the clinical usefulness and limitation of CMR for identifying myocardial damage in the survivors of OHCA in midtown.METHODS Nineteen patients underwent CMR to detect myocardial damage related to OHCA in the midtown of a capital city.Cine,T1 and T2 mapping,T2-weighted,and late gadolinium enhancement(LGE)imaging were acquired using a 1.5 T scanner.We described the clinical characteristics of the survivors of OHCA and evaluated usefulness of CMR for identifying myocardial damage related to OHCA.RESULTS Among 19 patients experiencing OHCA,7 experienced it in trains or on railway platforms,4 while practicing sports,and 4 during their daily work.Ten of the 19 survivors were diagnosed with coronary vasospasm(CVS),in whom CMR failed to depict its characteristic findings.CMR was useful for identifying myocardial damage associated with hypertrophic cardiomyopathy(HCM)or myocardial infarction(MI).LGE was related to serious ventricular arrhythmias after implantable cardioverter defibrillator(ICD)installation in 3 patients(CVS,2;HCM,1).CONCLUSION CMR is useful for identifying myocardial damage of HCM or MI inducing OHCA and predicting ventricular arrhythmias after ICD implantation but has limited capability for detecting myocardial damage of CVS.