BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring except...BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.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
Background:Magnetic resonance spectroscopy(MRS)represents a significant advancement in the noninvasive assessment of brain metabolism.MRS can provide valuable metabolic information and facilitate more accurate diagnos...Background:Magnetic resonance spectroscopy(MRS)represents a significant advancement in the noninvasive assessment of brain metabolism.MRS can provide valuable metabolic information and facilitate more accurate diagnoses of intrauterine fetal brain development than was previously possible.To obtain information regarding normal intrauterine fetal brain metabolism and to establish gestational age-specific reference values for normal fetal brain metabolites for subsequent use in MRS,we conducted MRS scans of normal fetal brains during mid-to late-term pregnancies,along with related processing.Methods:In this prospective study,MRS scans were conducted on 109 fetuses,with a total of 54 normal fetal brains enrolled on the basis of specific inclusion and exclusion criteria.We analyzed metabolic ratios,including the sum of N-acetylaspartate(NAA)and total N-acetylaspartate(tNAA),total choline(tCho),inositol(Ins),and total creatine(tCr),in relation to gestational age.Results:Gestational age was significantly correlated with specific metabolic ratios(Ins/tCr:r=-0.75,p<0.0001;tCho/tCr:r=-0.50,p<0.0001),especially tNAA/tCho(tNAA/tCho:r=0.54,p<0.0001)and tNAA/Ins(r=0.56,p<0.0001),providing a baseline for fetal brain metabolic assessment.Linear regression analysis was used to calculate regression lines for fetal brain metabolite ratios.Slopes were tested at p of 0.05.Conclusions:The current findings confirmed a significant correlation between fetal brain metabolites and gestational age,supporting the feasibility of establishing standard values for these metabolites in fetal brain assessment.展开更多
Objectives:Nurses working in critical care units may encounter substantial work-related strain,and elevated levels of stress can lead to burnout,ultimately impacting both the quality of nursing care and their overall ...Objectives:Nurses working in critical care units may encounter substantial work-related strain,and elevated levels of stress can lead to burnout,ultimately impacting both the quality of nursing care and their overall working experience.This study aimed to assess job burnout and determine the factors that contribute to it among critical care nurses in the Eastern Province of Saudi Arabia.Methods:This study employed a descriptive,exploratory,cross-sectional research design.A total of 220 nurses employed in the critical care units of 5 private hospitals in the eastern region were selected for participation in this study using a convenience sample method.An electronic survey was distributed to critical care nurses in the Eastern Province who satisfied the specified inclusion criteria.The job burnout questionnaire utilized in this study was derived from previously conducted research,which has been established as a reliable and valid survey instrument.The process of data analysis was conducted utilizing the SPSS program.The scientific research conducted on human subjects adhered rigorously to all ethical considerations.Results:The highest percentage of nurses at the critical care units reported experiencing moderate levels of job burnout.Nurses exhibiting greater levels of professional experience demonstrated a statistically significant reduction in overall burnout scores when compared to their less experienced counterparts.Furthermore,within the realm of sociodemographic factors,it was found that the only significant independent predictor for job burnout was the level of experience among critical care nurses.Conclusions:The prevalence of burnout among nurses in critical care settings was found to be significant,with most participants reporting moderate levels of burnout which can yield significant ramifications for nurses and healthcare professionals.Consequently,healthcare organizations must accord primacy to the welfare of their staff and adopt proactive strategies to mitigate job burnout.展开更多
Liver transplantation(LT)has made significant progress in the treatment of end stage liver disease(ESLD).However,many patients still die from disease progression while awaiting transplantation.As the number of patient...Liver transplantation(LT)has made significant progress in the treatment of end stage liver disease(ESLD).However,many patients still die from disease progression while awaiting transplantation.As the number of patients on LT waiting lists is increasing,and the organ shortage crisis is obvious,various efforts have been made to increase the pool of available liver grafts[1].In addition to living donor liver transplantation(LDLT),improving the utilization rate of extended criteria donor(ECD)livers is an important way.However,under traditional cold storage,ECD livers are usually associated with a higher risk of ischemic biliary disease,early allograft dysfunction(EAD)or even primary nonfunction(PNF).The frequently described definition in the literature for ECD grafts generally includes elderly,steatotic,long cold ischemia time(CIT),grafts obtained from donation after circulatory death(DCD),split liver grafts,donors with increased risk of infectious disease transmission and prolonged donor intensive care unit stay[2].展开更多
The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of neuroinflammation.While current studies primarily attribute its effects to neurons and glial ce...The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of neuroinflammation.While current studies primarily attribute its effects to neurons and glial cells,emerging research suggests that cGAS-STING signaling may play a critical role in cerebral vasculature,particularly in brain endothelial cells.Therefore,studying the role 7of inflammation caused by the cGAS-STING pathway in brain endothelial cells could provide a more comprehensive understanding of neuroinflammatory disease and new avenues for therapeutic interventions.Here,we review the multifaceted role of global cGAS-STING signaling in various neurological and neuroinflammatory diseases and the potential contribution of cGAS-STING in brain endothelial cells.展开更多
Objective To investigate the association between ABO blood types and gestational diabetes mellitus(GDM)risk.Methods A prospective birth cohort study was conducted.ABO blood types were determined using the slide method...Objective To investigate the association between ABO blood types and gestational diabetes mellitus(GDM)risk.Methods A prospective birth cohort study was conducted.ABO blood types were determined using the slide method.GDM diagnosis was based on a 75-g,2-h oral glucose tolerance test(OGTT)according to the criteria of the International Association of Diabetes and Pregnancy Study Groups.Logistic regression was applied to calculate the odds ratios(ORs)and 95%confidence intervals(CIs)between ABO blood types and GDM risk.Results A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study.The ABO blood types distribution was:type O(30.99%),type A(26.58%),type B(32.20%),and type AB(10.23%).GDM was identified in 14.44%of participants.Using blood type O as a reference,GDM risk was not significantly higher for types A(OR=1.05)or B(OR=1.04).However,women with type AB had a 19%increased risk of GDM(OR=1.19,95%CI=1.05–1.34;P<0.05),even after adjusting for various factors.This increased risk for type AB was consistent across subgroup and sensitivity analyses.Conclusion The ABO blood types may influence GDM risk,with type AB associated with a higher risk.Incorporating it—either as a single risk factor or in combination with other known factors—could help identify individuals at risk for GDM before or during early pregnancy.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
Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was...Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed.LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth.The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)database.Additionally,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines.The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD.Additionally,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression.Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 overexpression.Conclusions:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.展开更多
Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela ...Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.展开更多
BACKGROUND The need for an emergency upgrade of a hospitalized trauma patient from the floor to the trauma intensive care unit(ICU)is an unanticipated event with possible life-threatening consequences.Unplanned ICU ad...BACKGROUND The need for an emergency upgrade of a hospitalized trauma patient from the floor to the trauma intensive care unit(ICU)is an unanticipated event with possible life-threatening consequences.Unplanned ICU admissions are associated with increased morbidity and mortality and are an indicator of trauma service quality.Two different types of unplanned ICU admissions include upgrades(patients admitted to the floor then moved to the ICU)and bounce backs(patients admitted to the ICU,discharged to the floor,and then readmitted to the ICU).Previous studies have shown that geriatric trauma patients are at higher risk for unfavorable outcomes.AIM To analyze the characteristics,management and outcomes of trauma patients who had an unplanned ICU admission during their hospitalization.METHODS This institutional review board approved,retrospective cohort study examined 203 adult trauma patients with unplanned ICU admission at an urban level 1 trauma center over a six-year period(2017-2023).This included 134 upgrades and 69 bounce backs.Analyzed variables included:(1)Age;(2)Sex;(3)Comorbidities;(4)Mechanism of injury(MOI);(5)Injury severity score(ISS);(6)Glasgow Coma Scale(GCS);(7)Type of injury;(8)Transfusions;(9)Consultations;(10)Timing and reason for unplanned admission;(11)Intubations;(12)Surgical interventions;(13)ICU and hospital lengths of stay;and(14)Mortality.RESULTS Unplanned ICU admissions comprised 4.2%of total ICU admissions.Main MOI was falls.Mean age was 70.7 years,ISS was 12.8 and GCS was 13.9.Main injuries were traumatic brain injury(37.4%)and thoracic injury(21.7%),and main reason for unplanned ICU admission was respiratory complication(39.4%).The 47.3%underwent a surgical procedure and 46.8%were intubated.Average timing for unplanned ICU admission was 2.9 days.Bounce backs occurred half as often as upgrades,however had higher rates of transfusions(63.8%vs 40.3%,P=0.002),consultations(4.8 vs 3.0,P<0.001),intubations(63.8%vs 38.1%%,P=0.001),longer ICU lengths of stay(13.2 days vs 6.4 days,P<0.001)and hospital lengths of stay(26.7 days vs 13.0 days,P<0.001).Mortality was 25.6%among unplanned ICU admissions,31.9%among geriatric unplanned ICU admissions and 11.9%among all trauma ICU patients.CONCLUSION Unplanned ICU admissions constituted 4.2%of total ICU admissions.Respiratory complications were the main cause of unplanned ICU admissions.Bounce backs occurred half as often as upgrades,but were associated with worse outcomes.展开更多
In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reverse...In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reversed osimertinib resistance in non-small cell lung cancer(NSCLC).Therefore,we performed immunohistochemical analyses on tumor tissues from three NSCLC patients with osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A(VEGFA)before and after the development of osimertinib resistance.The results revealed the downregulation of E-cadherin,coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance,compared with those in tissues from patients before receiving osimertinib.Subsequently,we established osimertinib-resistant(Osi-R)cell lines and found that the Osi-R cells acquired EMT features.Next,we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT.The expression levels of VEGFA and tube formation were analyzed in the combination group in vitro.Finally,we determined the reversal of osimertinib resistance by the combination of osimertinib and anlotinib in vivo using 20 nude mice.The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of Osi-R cells,inhibited tumor growth,exerted antitumor activity,and ultimately reversed osimertinib resistance in mice.The co-administration of osimertinib and anlotinib demonstrated synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients,ultimately reversing osimertinib resistance.展开更多
Emergency department nurses face severe occupational stress leading to anxiety,depression,and burnout,which significantly impair their well-being and patientcare quality.This narrative review examined the role of mind...Emergency department nurses face severe occupational stress leading to anxiety,depression,and burnout,which significantly impair their well-being and patientcare quality.This narrative review examined the role of mindfulness-based stress reduction(MBSR)in addressing these challenges.Rooted in nonjudgmental present-moment awareness,MBSR enhances emotional regulation and reduces psychological distress by fostering adaptive coping strategies.Studies have demonstrated its efficacy in lowering anxiety,depressive symptoms,and emotional exhaustion,while improving workplace well-being,empathy,and job satisfaction.Mechanistically,MBSR improves interoceptive awareness and autonomic balance,as evidenced by physiological markers such as heart rate variability.However,gaps remain in long-term efficacy assessments,personalized interventions,and integration with multidisciplinary approaches.Future research should prioritize tailored biomarker-driven programs,longitudinal studies,and scalable implementation strategies in high-stress clinical settings.This review underscores MBSR’s potential as a sustainable,evidence-based tool to enhance emergency department nurses’mental health and professional performance,advocating for broader adoption and further refinement of its practical applications.展开更多
In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence ...In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment effect.For any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real change.Using structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each patient.Having mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given condition.There are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their differences.This article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.展开更多
BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis th...BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.展开更多
A pregnant woman underwent fetal brain magnetic resonance imaging(MRI)following ultrasound detection of a posterior fossa cyst at 29 weeks'gestation.She presented with no relevant medical history and underwent a r...A pregnant woman underwent fetal brain magnetic resonance imaging(MRI)following ultrasound detection of a posterior fossa cyst at 29 weeks'gestation.She presented with no relevant medical history and underwent a routine obstetric examination during pregnancy.The fetal head position,fetal cranial development,and limb development remained normal until 29 weeks.展开更多
There exists a notion that there is an obesity paradox in the prognosis of community-acquired pneumonia.In other words,obese individuals with communityacquired pneumonia have a better prognosis.The study by Wang et al...There exists a notion that there is an obesity paradox in the prognosis of community-acquired pneumonia.In other words,obese individuals with communityacquired pneumonia have a better prognosis.The study by Wang et al supports this claim,but we believe that the obesity paradox should not be proposed hastily as it is influenced by numerous subjective and objective confounding factors.展开更多
BACKGROUND Malignant transformation(MT)of mature cystic teratoma(MCT)has a poor prognosis,especially in advanced cases.Concurrent chemoradiotherapy(CCRT)has an inhibitory effect on MT.CASE SUMMARY Herein,we present a ...BACKGROUND Malignant transformation(MT)of mature cystic teratoma(MCT)has a poor prognosis,especially in advanced cases.Concurrent chemoradiotherapy(CCRT)has an inhibitory effect on MT.CASE SUMMARY Herein,we present a case in which CCRT had a reduction effect preoperatively.A 73-year-old woman with pyelonephritis was referred to our hospital.Computed tomography revealed right hydronephrosis and a 6-cm pelvic mass.Endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB)revealed squamous cell carci-noma.The patient was diagnosed with MT of MCT.Due to her poor general con-dition and renal malfunction,we selected CCRT,expecting fewer adverse effects.After CCRT,her performance status improved,and the tumor size was reduced;surgery was performed.Five months postoperatively,the patient developed dis-semination and lymph node metastases.Palliative chemotherapy was ineffective.She died 18 months after treatment initiation.CONCLUSION EUS-FNB was useful in the diagnosis of MT of MCT;CCRT suppressed the disea-se and improved quality of life.展开更多
Background Caffeic acid(CA)and its derivative,chlorogenic acid(CGA),have shown promise in preventing and alleviating fatty liver disease.CA,compared to CGA,has much lower production costs and higher bioavailability,ma...Background Caffeic acid(CA)and its derivative,chlorogenic acid(CGA),have shown promise in preventing and alleviating fatty liver disease.CA,compared to CGA,has much lower production costs and higher bioavailability,making it a potentially superior feed additive.However,the efficacy,mechanistic differences,and comparative impacts of CA and CGA on fatty liver disease in laying hens remain unclear.This study aimed to evaluate and compare the effects of CA and CGA on production performance,egg quality,and fatty liver disease in laying hens.Results A total of 1,44061-week-old Hyline Brown laying hens were randomly divided into 8 groups and fed diets supplemented with basal diet,25,50,100 and 200 mg/kg of CA,and 100,200 and 400 mg/kg of CGA(CON,CA25,CA50,CA100,CA200,CGA100,CGA200 and CGA400,respectively)for 12 weeks.Both CA and CGA improved production performance and egg quality,while reducing markers of hepatic damage and lipid accumulation.CA and CGA significantly decreased TG,TC,and LDL-C levels and increased T-SOD activity.Transcriptomic and proteomic analyses revealed that CA and CGA reduced hepatic lipid accumulation through downregulation of lipid biosynthesis-related genes(ACLY,ACACA,FASN,and SCD1)and enhanced lipid transport and oxidation genes(FABPs,CD36,CPT1A,ACOX1,and SCP2).Of note,low-dose CA25 exhibited equivalent efficacy to the higher dose CGA100 group in alleviating fatty liver conditions.Mechanistically,CA and CGA alleviated lipid accumulation via activation of the ADPN-AMPK-PPARαsignaling pathway.Conclusions This study demonstrates that dietary CA and CGA effectively improve laying performance,egg quality,and hepatic lipid metabolism in laying hens,with CA potentially being more economical and efficient.Transcriptomic and proteomic evidence highlight shared mechanisms between CA25 and CGA100.These findings provide a foundation for CA and CGA as therapeutic agents for fatty liver disease and related metabolic diseases in hens,and also offer insights into the targeted modification of CGA(including the isomer of CGA)into CA,thereby providing novel strategies for the efficient utilization of CGA.Highlights(1)Dietary CA and CGA improve fatty liver,laying performance and egg quality.(2)Lower dose of CA25 achieves the equivalent improvement as CGA100 or CGA200.(3)CA and CGA mediate the ADPN-AMPK-PPARαpathway to alleviate fatty liver.展开更多
文摘BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.
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 China Society for Maternal and Child Health Research(Gant/Award Number:2023CAMCHS003A17).
文摘Background:Magnetic resonance spectroscopy(MRS)represents a significant advancement in the noninvasive assessment of brain metabolism.MRS can provide valuable metabolic information and facilitate more accurate diagnoses of intrauterine fetal brain development than was previously possible.To obtain information regarding normal intrauterine fetal brain metabolism and to establish gestational age-specific reference values for normal fetal brain metabolites for subsequent use in MRS,we conducted MRS scans of normal fetal brains during mid-to late-term pregnancies,along with related processing.Methods:In this prospective study,MRS scans were conducted on 109 fetuses,with a total of 54 normal fetal brains enrolled on the basis of specific inclusion and exclusion criteria.We analyzed metabolic ratios,including the sum of N-acetylaspartate(NAA)and total N-acetylaspartate(tNAA),total choline(tCho),inositol(Ins),and total creatine(tCr),in relation to gestational age.Results:Gestational age was significantly correlated with specific metabolic ratios(Ins/tCr:r=-0.75,p<0.0001;tCho/tCr:r=-0.50,p<0.0001),especially tNAA/tCho(tNAA/tCho:r=0.54,p<0.0001)and tNAA/Ins(r=0.56,p<0.0001),providing a baseline for fetal brain metabolic assessment.Linear regression analysis was used to calculate regression lines for fetal brain metabolite ratios.Slopes were tested at p of 0.05.Conclusions:The current findings confirmed a significant correlation between fetal brain metabolites and gestational age,supporting the feasibility of establishing standard values for these metabolites in fetal brain assessment.
文摘Objectives:Nurses working in critical care units may encounter substantial work-related strain,and elevated levels of stress can lead to burnout,ultimately impacting both the quality of nursing care and their overall working experience.This study aimed to assess job burnout and determine the factors that contribute to it among critical care nurses in the Eastern Province of Saudi Arabia.Methods:This study employed a descriptive,exploratory,cross-sectional research design.A total of 220 nurses employed in the critical care units of 5 private hospitals in the eastern region were selected for participation in this study using a convenience sample method.An electronic survey was distributed to critical care nurses in the Eastern Province who satisfied the specified inclusion criteria.The job burnout questionnaire utilized in this study was derived from previously conducted research,which has been established as a reliable and valid survey instrument.The process of data analysis was conducted utilizing the SPSS program.The scientific research conducted on human subjects adhered rigorously to all ethical considerations.Results:The highest percentage of nurses at the critical care units reported experiencing moderate levels of job burnout.Nurses exhibiting greater levels of professional experience demonstrated a statistically significant reduction in overall burnout scores when compared to their less experienced counterparts.Furthermore,within the realm of sociodemographic factors,it was found that the only significant independent predictor for job burnout was the level of experience among critical care nurses.Conclusions:The prevalence of burnout among nurses in critical care settings was found to be significant,with most participants reporting moderate levels of burnout which can yield significant ramifications for nurses and healthcare professionals.Consequently,healthcare organizations must accord primacy to the welfare of their staff and adopt proactive strategies to mitigate job burnout.
文摘Liver transplantation(LT)has made significant progress in the treatment of end stage liver disease(ESLD).However,many patients still die from disease progression while awaiting transplantation.As the number of patients on LT waiting lists is increasing,and the organ shortage crisis is obvious,various efforts have been made to increase the pool of available liver grafts[1].In addition to living donor liver transplantation(LDLT),improving the utilization rate of extended criteria donor(ECD)livers is an important way.However,under traditional cold storage,ECD livers are usually associated with a higher risk of ischemic biliary disease,early allograft dysfunction(EAD)or even primary nonfunction(PNF).The frequently described definition in the literature for ECD grafts generally includes elderly,steatotic,long cold ischemia time(CIT),grafts obtained from donation after circulatory death(DCD),split liver grafts,donors with increased risk of infectious disease transmission and prolonged donor intensive care unit stay[2].
基金partially supported by a grant(RF1AG059694)from the U.S.National Institutes of Healthby Polytrauma System of Care,VAPAHCS(to JL)。
文摘The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of neuroinflammation.While current studies primarily attribute its effects to neurons and glial cells,emerging research suggests that cGAS-STING signaling may play a critical role in cerebral vasculature,particularly in brain endothelial cells.Therefore,studying the role 7of inflammation caused by the cGAS-STING pathway in brain endothelial cells could provide a more comprehensive understanding of neuroinflammatory disease and new avenues for therapeutic interventions.Here,we review the multifaceted role of global cGAS-STING signaling in various neurological and neuroinflammatory diseases and the potential contribution of cGAS-STING in brain endothelial cells.
基金supported by the Capital’s Funds for Health Improvement and Research(No.2024-2G-2118)the National Key Research and Development Program of China(2016YFC1000101)+2 种基金the Leading Talents in the Construction Project of High-Level Public Health Technical Talents in Beijing(2022-1-003)the“Green Seedling”Youth Program by the Beijing Hospitals Authority(QML20231402)the Young Elite Scientist Sponsorship Program by the Beijing Association for Science and Technology(BYESS2022200)。
文摘Objective To investigate the association between ABO blood types and gestational diabetes mellitus(GDM)risk.Methods A prospective birth cohort study was conducted.ABO blood types were determined using the slide method.GDM diagnosis was based on a 75-g,2-h oral glucose tolerance test(OGTT)according to the criteria of the International Association of Diabetes and Pregnancy Study Groups.Logistic regression was applied to calculate the odds ratios(ORs)and 95%confidence intervals(CIs)between ABO blood types and GDM risk.Results A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study.The ABO blood types distribution was:type O(30.99%),type A(26.58%),type B(32.20%),and type AB(10.23%).GDM was identified in 14.44%of participants.Using blood type O as a reference,GDM risk was not significantly higher for types A(OR=1.05)or B(OR=1.04).However,women with type AB had a 19%increased risk of GDM(OR=1.19,95%CI=1.05–1.34;P<0.05),even after adjusting for various factors.This increased risk for type AB was consistent across subgroup and sensitivity analyses.Conclusion The ABO blood types may influence GDM risk,with type AB associated with a higher risk.Incorporating it—either as a single risk factor or in combination with other known factors—could help identify individuals at risk for GDM before or during early pregnancy.
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 2022 Natural Science Foundation of Fujian Province(No.2022J011486).
文摘Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed.LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth.The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)database.Additionally,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines.The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD.Additionally,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression.Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 overexpression.Conclusions:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.
文摘Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.
文摘BACKGROUND The need for an emergency upgrade of a hospitalized trauma patient from the floor to the trauma intensive care unit(ICU)is an unanticipated event with possible life-threatening consequences.Unplanned ICU admissions are associated with increased morbidity and mortality and are an indicator of trauma service quality.Two different types of unplanned ICU admissions include upgrades(patients admitted to the floor then moved to the ICU)and bounce backs(patients admitted to the ICU,discharged to the floor,and then readmitted to the ICU).Previous studies have shown that geriatric trauma patients are at higher risk for unfavorable outcomes.AIM To analyze the characteristics,management and outcomes of trauma patients who had an unplanned ICU admission during their hospitalization.METHODS This institutional review board approved,retrospective cohort study examined 203 adult trauma patients with unplanned ICU admission at an urban level 1 trauma center over a six-year period(2017-2023).This included 134 upgrades and 69 bounce backs.Analyzed variables included:(1)Age;(2)Sex;(3)Comorbidities;(4)Mechanism of injury(MOI);(5)Injury severity score(ISS);(6)Glasgow Coma Scale(GCS);(7)Type of injury;(8)Transfusions;(9)Consultations;(10)Timing and reason for unplanned admission;(11)Intubations;(12)Surgical interventions;(13)ICU and hospital lengths of stay;and(14)Mortality.RESULTS Unplanned ICU admissions comprised 4.2%of total ICU admissions.Main MOI was falls.Mean age was 70.7 years,ISS was 12.8 and GCS was 13.9.Main injuries were traumatic brain injury(37.4%)and thoracic injury(21.7%),and main reason for unplanned ICU admission was respiratory complication(39.4%).The 47.3%underwent a surgical procedure and 46.8%were intubated.Average timing for unplanned ICU admission was 2.9 days.Bounce backs occurred half as often as upgrades,however had higher rates of transfusions(63.8%vs 40.3%,P=0.002),consultations(4.8 vs 3.0,P<0.001),intubations(63.8%vs 38.1%%,P=0.001),longer ICU lengths of stay(13.2 days vs 6.4 days,P<0.001)and hospital lengths of stay(26.7 days vs 13.0 days,P<0.001).Mortality was 25.6%among unplanned ICU admissions,31.9%among geriatric unplanned ICU admissions and 11.9%among all trauma ICU patients.CONCLUSION Unplanned ICU admissions constituted 4.2%of total ICU admissions.Respiratory complications were the main cause of unplanned ICU admissions.Bounce backs occurred half as often as upgrades,but were associated with worse outcomes.
基金supported by the National Natural Science Foundation of China(Grant Nos.82172728,82370096).
文摘In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reversed osimertinib resistance in non-small cell lung cancer(NSCLC).Therefore,we performed immunohistochemical analyses on tumor tissues from three NSCLC patients with osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A(VEGFA)before and after the development of osimertinib resistance.The results revealed the downregulation of E-cadherin,coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance,compared with those in tissues from patients before receiving osimertinib.Subsequently,we established osimertinib-resistant(Osi-R)cell lines and found that the Osi-R cells acquired EMT features.Next,we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT.The expression levels of VEGFA and tube formation were analyzed in the combination group in vitro.Finally,we determined the reversal of osimertinib resistance by the combination of osimertinib and anlotinib in vivo using 20 nude mice.The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of Osi-R cells,inhibited tumor growth,exerted antitumor activity,and ultimately reversed osimertinib resistance in mice.The co-administration of osimertinib and anlotinib demonstrated synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients,ultimately reversing osimertinib resistance.
文摘Emergency department nurses face severe occupational stress leading to anxiety,depression,and burnout,which significantly impair their well-being and patientcare quality.This narrative review examined the role of mindfulness-based stress reduction(MBSR)in addressing these challenges.Rooted in nonjudgmental present-moment awareness,MBSR enhances emotional regulation and reduces psychological distress by fostering adaptive coping strategies.Studies have demonstrated its efficacy in lowering anxiety,depressive symptoms,and emotional exhaustion,while improving workplace well-being,empathy,and job satisfaction.Mechanistically,MBSR improves interoceptive awareness and autonomic balance,as evidenced by physiological markers such as heart rate variability.However,gaps remain in long-term efficacy assessments,personalized interventions,and integration with multidisciplinary approaches.Future research should prioritize tailored biomarker-driven programs,longitudinal studies,and scalable implementation strategies in high-stress clinical settings.This review underscores MBSR’s potential as a sustainable,evidence-based tool to enhance emergency department nurses’mental health and professional performance,advocating for broader adoption and further refinement of its practical applications.
文摘In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment effect.For any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real change.Using structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each patient.Having mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given condition.There are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their differences.This article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.
基金Supported by The National Natural Science Foundation of China,No.82350127 and No.82241013the Shanghai Natural Science Foundation,No.20ZR1411600+2 种基金the Shanghai Shenkang Hospital Development Center,No.SHDC2020CR4039the Bethune Ethicon Excellent Surgery Foundation,No.CESS2021TC04Xuhui District Medical Research Project of Shanghai,No.SHXH201805.
文摘BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.
基金supported by China Society for Maternal and Child Health Research(Grant/Award Number:2023CAMCHS003A17).
文摘A pregnant woman underwent fetal brain magnetic resonance imaging(MRI)following ultrasound detection of a posterior fossa cyst at 29 weeks'gestation.She presented with no relevant medical history and underwent a routine obstetric examination during pregnancy.The fetal head position,fetal cranial development,and limb development remained normal until 29 weeks.
文摘There exists a notion that there is an obesity paradox in the prognosis of community-acquired pneumonia.In other words,obese individuals with communityacquired pneumonia have a better prognosis.The study by Wang et al supports this claim,but we believe that the obesity paradox should not be proposed hastily as it is influenced by numerous subjective and objective confounding factors.
文摘BACKGROUND Malignant transformation(MT)of mature cystic teratoma(MCT)has a poor prognosis,especially in advanced cases.Concurrent chemoradiotherapy(CCRT)has an inhibitory effect on MT.CASE SUMMARY Herein,we present a case in which CCRT had a reduction effect preoperatively.A 73-year-old woman with pyelonephritis was referred to our hospital.Computed tomography revealed right hydronephrosis and a 6-cm pelvic mass.Endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB)revealed squamous cell carci-noma.The patient was diagnosed with MT of MCT.Due to her poor general con-dition and renal malfunction,we selected CCRT,expecting fewer adverse effects.After CCRT,her performance status improved,and the tumor size was reduced;surgery was performed.Five months postoperatively,the patient developed dis-semination and lymph node metastases.Palliative chemotherapy was ineffective.She died 18 months after treatment initiation.CONCLUSION EUS-FNB was useful in the diagnosis of MT of MCT;CCRT suppressed the disea-se and improved quality of life.
基金supported by National Key R&D Program of China(2023YFD1301200)China Agriculture Research Systems(CARS-40-K11)+2 种基金Beijing Agriculture Innovation Consortium(BAIC06-2024-G05)Strategic Priority Research Program of the National Center of Technology Innovation for Pigs(NCTIP-XD/C08)The Chinese Academy of Agricultural Science and Technology Innovation Project(ASTIP-IAS-12)。
文摘Background Caffeic acid(CA)and its derivative,chlorogenic acid(CGA),have shown promise in preventing and alleviating fatty liver disease.CA,compared to CGA,has much lower production costs and higher bioavailability,making it a potentially superior feed additive.However,the efficacy,mechanistic differences,and comparative impacts of CA and CGA on fatty liver disease in laying hens remain unclear.This study aimed to evaluate and compare the effects of CA and CGA on production performance,egg quality,and fatty liver disease in laying hens.Results A total of 1,44061-week-old Hyline Brown laying hens were randomly divided into 8 groups and fed diets supplemented with basal diet,25,50,100 and 200 mg/kg of CA,and 100,200 and 400 mg/kg of CGA(CON,CA25,CA50,CA100,CA200,CGA100,CGA200 and CGA400,respectively)for 12 weeks.Both CA and CGA improved production performance and egg quality,while reducing markers of hepatic damage and lipid accumulation.CA and CGA significantly decreased TG,TC,and LDL-C levels and increased T-SOD activity.Transcriptomic and proteomic analyses revealed that CA and CGA reduced hepatic lipid accumulation through downregulation of lipid biosynthesis-related genes(ACLY,ACACA,FASN,and SCD1)and enhanced lipid transport and oxidation genes(FABPs,CD36,CPT1A,ACOX1,and SCP2).Of note,low-dose CA25 exhibited equivalent efficacy to the higher dose CGA100 group in alleviating fatty liver conditions.Mechanistically,CA and CGA alleviated lipid accumulation via activation of the ADPN-AMPK-PPARαsignaling pathway.Conclusions This study demonstrates that dietary CA and CGA effectively improve laying performance,egg quality,and hepatic lipid metabolism in laying hens,with CA potentially being more economical and efficient.Transcriptomic and proteomic evidence highlight shared mechanisms between CA25 and CGA100.These findings provide a foundation for CA and CGA as therapeutic agents for fatty liver disease and related metabolic diseases in hens,and also offer insights into the targeted modification of CGA(including the isomer of CGA)into CA,thereby providing novel strategies for the efficient utilization of CGA.Highlights(1)Dietary CA and CGA improve fatty liver,laying performance and egg quality.(2)Lower dose of CA25 achieves the equivalent improvement as CGA100 or CGA200.(3)CA and CGA mediate the ADPN-AMPK-PPARαpathway to alleviate fatty liver.
