Search

Mouse hippocampus retains the capacity for neurogenesis throughout lifetime, but such plasticity decreases with age. Adult hippocampal neurogenesis (AHN) involves the birth, maturation, and synaptic integration of newborn granule cells (GCs) into preexisting hippocampal circuitry. While functional integration onto adult-born GCs has been extensively studied, maturation of efferent projections onto CA3 pyramidal cells is less understood, particularly in aged brain. Here, using combined light and reconstructive electron microscopy (EM), we describe the maturation of mossy fiber bouton (MFB) connectivity with CA3 pyramidal cells in young adult and aged mouse brain. We found mature synaptic contacts of newborn GCs were formed in both young and aged brains. However, the dynamics of their spatiotemporal development and the cellular process by which these cells functionally integrated over time were different. In young brain newborn GCs either formed independent nascent MFB synaptic contacts or replaced preexisting MFBs, but these contacts were pruned over time to a mature state. In aged brain only replacement of preexisting MFBs was observed and new contacts were without evidence of pruning. These data illustrate that functional synaptic integration of AHN occurs in young adult and aged brain, but with distinct dynamics. They suggest elimination of preexisting connectivity is required for the integration of adult-born GCs in aged brain.

Arginase deficiency is caused by biallelic mutations in arginase 1 (ARG1), the final step of the urea cycle, and results biochemically in hyperargininemia and the presence of guanidino compounds, while it is clinically notable for developmental delays, spastic diplegia, psychomotor function loss, and (uncommonly) death. There is currently no completely effective medical treatment available. While preclinical strategies have been demonstrated, disadvantages with viral-based episomal-expressing gene therapy vectors include the risk of insertional mutagenesis and limited efficacy due to hepatocellular division. Recent advances in messenger RNA (mRNA) codon optimization, synthesis, and encapsulation within biodegradable liver-targeted lipid nanoparticles (LNPs) have potentially enabled a new generation of safer, albeit temporary, treatments to restore liver metabolic function in patients with urea cycle disorders, including ARG1 deficiency. In this study, we applied such technologies to successfully treat an ARG1-deficient murine model. Mice were administered LNPs encapsulating human codon-optimized ARG1 mRNA every 3 d. Mice demonstrated 100% survival with no signs of hyperammonemia or weight loss to beyond 11 wk, compared with controls that perished by day 22. Plasma ammonia, arginine, and glutamine demonstrated good control without elevation of guanidinoacetic acid, a guanidino compound. Evidence of urea cycle activity restoration was demonstrated by the ability to fully metabolize an ammonium challenge and by achieving near-normal ureagenesis; liver arginase activity achieved 54% of wild type. Biochemical and microscopic data showed no evidence of hepatotoxicity. These results suggest that delivery of ARG1 mRNA by liver-targeted nanoparticles may be a viable gene-based therapeutic for the treatment of arginase deficiency.

Objectives: The aim of this study was to systematically assess the methodological quality of current sepsis infection management guidelines and identify gaps in knowledge that limit evidence-based practice. Methods: A systematic search was conducted to obtain guidelines for the management of sepsis infections (2012–2021), and three reviewers independently assessed the quality of eligible guidelines using Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. The intraclass correlation coefficients (ICCs) were used to measure the agreement between reviewers. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to analyze the strength of recommendation and level of evidence of the guideline, and the number of recommendations, strength of recommendation, and level of evidence were determined. Results: Eleven guidelines for the management of sepsis infection were identified. An overall high agreement among the evaluators for each domain was observed (ICC ranged from 0.850 to 0.959). The overall scores of the included guidelines were all over 60% (range, 62.3-89.90%), which were worthy of recommendation for clinical use; among them, 4 guidelines had an overall score of over 80%, which were high-quality guideline articles. In terms of the quality domains of the guidelines, the scope and purpose domain and the clarity of expression domain had the highest average scores, which were 93.6% (range, 79.6–98.1%) and 91.4% (range, 64.8–98.1%), respectively, while the applicability domain had the lowest average score, which was 64.8% (range, 51.4–76.4%). The strength of the recommendations of the guideline recommendations was mainly weak, accounting for 73.4%; the level of evidence cited was mainly very low quality (60.2%) and low quality (28.1%). Conclusions: The quality of sepsis infection management guidelines varies, but the overall quality level is satisfactory. Improving the low-quality areas of sepsis guidelines, attempting to resolve existing problems and controversies, and improving the quality of research evidence will be effective ways for developers to upgrade sepsis guidelines. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) together occur frequently among the elderly population. However, the inconsistency in assessments and limited medical resources in the community make it challenging to identify depression in patients with T2DM. This cross-sectional study aimed to investigate the activation pattern and network connectivity of prefrontal cortex (PFC) during a verbal fluency task (VFT) in patients with T2DM and MDD using functional near-infrared spectroscopy (fNIRS). Methods: Three parallel groups (T2DM with MDD group, T2DM group, and healthy group) with 100 participants in each group were included in the study. Recruitment took place from August 1, 2020, to December 31, 2023. Due to the close association between the PFC and depressive emotions, fNIRS was used to monitor brain activation and network connectivity of PFC in all participants during a task of Chinese-language phonological VFT. Network-based statistic prediction was adopted as data analysis method. Results: Patients in the T2DM with MDD group showed characteristic activation pattern and network connectivity in contrast with patients with T2DM and healthy controls, including decreased activation in PFC, and decreased network connectivity of right dorsolateral prefrontal cortex (DLPFC). Furthermore, the network connectivity of the right DLPFC in patients with T2DM and MDD was negatively correlated with scores of Hamilton Depression Scale-24 (HAMD-24). Conclusions: There was a distinctive activation pattern and network connectivity of the PFC in patients with T2DM and MDD. The right DLPFC could serve as a potential target for the diagnosis and intervention of MDD in patients with T2DM. Plain Language Summary: As we all know, type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are highly prevalent and frequently coexist in older adults. The prevalence of MDD among individuals with T2DM has been reported to be as much as 28%. Practice guidelines from the American Diabetes Association and the World Health Organization recommend physicians should pay attention to depressive disorder in patients with T2DM. According to previous studies, functional near-infrared spectroscopy (fNIRS) may be a promising technique to objectively evaluate the functional changes of prefrontal cortex (PFC) in patients with T2DM and MDD. The preliminary study for this research "Characteristic changes of prefrontal and motor areas in patients with type 2 diabetes and major depressive disorder during a motor task of tai chi chuan: A functional near-infrared spectroscopy study" has already been published on Brain and Behavior. In this study, we utilized fNIRS system and planned to investigate the differences of activation, network connectivity and receiver-operating characteristic curve in the PFC among patients with T2DM and MDD, patients with T2DM, and healthy subjects during a verbal fluency task (VFT), aiming to confirm the characteristic activation pattern of PFC during VFT in patients with T2DM and MDD and identify the potential brain targets for intervention of depression in patients with T2DM. [ABSTRACT FROM AUTHOR]

An investigation of the multi-cycle dynamics of underwater explosion bubbles near hybrid boundaries is conducted using the experimental method. The experiments are carried out within a square steel tank. The free surface and a freely hanging steel plate comprise the hybrid boundary condition. Bubbles are initially positioned at equal distances from the two boundaries to facilitate a comparison of the relative influence exerted by each boundary. High-speed photography and pressure sensors are utilized to document the dynamics of bubbles and pressures in the flow field. An examination of the bubble behavior is conducted through the analysis of experimental imagery, elucidating the formation of a cone-shaped cavity near the free surface and the subsequent complex distortion behavior of the bubble as it interacts with the wall during the rebound phase. The investigation concentrates on the migratory properties of bubbles across various regions, revealing a spectrum of trajectories due to the varying boundary and buoyancy effects: vertical descent, "L"-shaped trajectory, "U"-shaped trajectory, and diagonal upward trajectory. Unless very close to the free surface, the direction of bubble migration changes at the end of each cycle due to local fragmentation of the bubble surface. Finally, the discussion culminated in an analysis of bubble energy conversion, revealing that the complex bubble behavior near the free surface weakens bubble collapse, resulting in minimal impact on the surrounding fluid dynamics from bubble oscillation. In the region distant from the free surface, when the bubble oscillation is weakly affected by buoyancy and boundaries, the energy emitted by bubble oscillation peaks due to the nearly spherical collapse. [ABSTRACT FROM AUTHOR]

Modification of the strength of excitatory synaptic connections is a fundamental mechanism by which neural circuits are refined during development and learning. Synapse Differentiation Induced Gene 1 (SynDIG1) has been shown to play a key role in regulating synaptic strength in vitro. Here, we investigated the role of SynDIG1 in vivo in mice with a disruption of the SynDIG1 gene rather than use an alternate loxP-flanked conditional mutant that we find retains a partial protein product. The gene-trap insertion with a reporter cassette mutant mice shows that the SynDIG1 promoter is active during embryogenesis in the retina with some activity in the brain, and postnatally in the mouse hippocampus, cortex, hindbrain, and spinal cord. Ultrastructural analysis of the hippocampal CA1 region shows a decrease in the average PSD length of synapses and a decrease in the number of synapses with a mature phenotype. Intriguingly, the total synapse number appears to be increased in SynDIG1 mutant mice. Electrophysiological analyses show a decrease in AMPA and NMDA receptor function in SynDIG1-deficient hippocampal neurons. Glutamate stimulation of individual dendritic spines in hippocampal slices from SynDIG1-deficient mice reveals increased short-term structural plasticity. Notably, the overall levels of PSD-95 or glutamate receptors enriched in postsynaptic biochemical fractions remain unaltered; however, activity-dependent synapse development is strongly compromised upon the loss of SynDIG1, supporting its importance for excitatory synapse maturation. Together, these data are consistent with a model in which SynDIG1 regulates the maturation of excitatory synapse structure and function in the mouse hippocampus in vivo.

UnlabelledArginase 1 deficiency is a urea cycle disorder associated with hyperargininemia, spastic diplegia, loss of ambulation, intellectual disability, and seizures. To gain insight on how loss of arginase expression affects the excitability and synaptic connectivity of the cortical neurons in the developing brain, we used anatomical, ultrastructural, and electrophysiological techniques to determine how single-copy and double-copy arginase deletion affects cortical circuits in mice. We find that the loss of arginase 1 expression results in decreased dendritic complexity, decreased excitatory and inhibitory synapse numbers, decreased intrinsic excitability, and altered synaptic transmission in layer 5 motor cortical neurons. Hepatic arginase 1 gene therapy using adeno-associated virus rescued nearly all these abnormalities when administered to neonatal homozygous knock-out animals. Therefore, gene therapeutic strategies can reverse physiological and anatomical markers of arginase 1 deficiency and therefore may be of therapeutic benefit for the neurological disabilities in this syndrome.Significance statementThese studies are one of the few investigations to try to understand the underlying neurological dysfunction that occurs in urea cycle disorders and the only to examine arginase deficiency. We have demonstrated by multiple modalities that, in murine layer 5 cortical neurons, a gradation of abnormalities exists based on the functional copy number of arginase: intrinsic excitability is altered, there is decreased density in asymmetrical and perisomatic synapses, and analysis of the dendritic complexity is lowest in the homozygous knock-out. With neonatal administration of adeno-associated virus expressing arginase, there is near-total recovery of the abnormalities in neurons and cortical circuits, supporting the concept that neonatal gene therapy may prevent the functional abnormalities that occur in arginase deficiency.

Astrocytes, once considered passive support cells, are increasingly appreciated as dynamic regulators of neuronal development and function, in part via secreted factors. The extent to which they similarly regulate oligodendrocytes or proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) is less understood. Here, we generated astrocytes from human pluripotent stem cells (hiPSC-Astros) and demonstrated that immature astrocytes, as opposed to mature ones, promote oligodendrogenesis in vitro. In the PVL mouse model of neonatal hypoxic/ischemic encephalopathy, associated with cerebral palsy in humans, transplanted immature hiPSC-Astros promoted myelinogenesis and behavioral outcome. We further identified TIMP-1 as a selectively upregulated component secreted from immature hiPSC-Astros. Accordingly, in the rat PVL model, intranasal administration of conditioned medium from immature hiPSC-Astros promoted oligodendrocyte maturation in a TIMP-1-dependent manner. Our findings suggest stage-specific developmental interactions between astroglia and oligodendroglia and have important therapeutic implications for promoting myelinogenesis.

BackgroundPeriventricular leukomalacia (PVL) is the leading cause of neurological disabilities including motor and cognitive deficits in premature infants. Periventricular leukomalacia is characterized by damage to the white matter in the immature brain, but the mechanisms by which damage to immature white matter results in widespread deficits of cognitive and motor function are unclear. The thalamocortical system is crucial for human consciousness and cognitive functions, and impaired development of the cortico-thalamic projections in the neonatal period is implicated to contribute importantly to abnormalities of cognitive function in children with PVL.ResultsIn this study, using a mouse model of PVL, we sought to test the hypothesis that PVL-like injury affects the different components of the thalamocortical circuitry that can be defined by vesicular glutamate transporters 1 and 2 (vGluT1 and vGluT2), both of which are required for glutamatergic synaptic transmission in the central nervous system. We combined immunocytochemistry and immuno-electron microscopy to investigate changes in cortico-thalamic synapses which were specifically identified by vGluT1 immunolabeling. We found that a drastic reduction in the density of vGluT1 labeled profiles in the somatosensory thalamus, with a reduction of 72-74 % in ventroposterior (VP) nucleus and a reduction of 42-82 % in thalamic reticular nucleus (RTN) in the ipsilateral side of PVL mice. We further examined these terminals at the electron microscopic level and revealed onefold-twofold decrease in the sizes of vGluT1 labeled corticothalamic terminals in VP and RTN. The present study provides anatomical and ultrastructural evidence to elucidate the cellular mechanisms underlying alteration of thalamic circuitry in a mouse model of PVL, and reveals that PVL-like injury has a direct impact on the corticothalamic projection system.ConclusionsOur findings provide the first set of evidence showing that the thalamocortical circuitry is affected and vulnerable in PVL mice, supporting a working model in which vGluT1 defined corticothalamic synapses are altered in PVL mice, and vGluT2 defined thalamocortical synapses are associated with such changes, leading to the compromised thalamocortical circuitry in the PVL mice. Our study demonstrates that the thalamocortical circuitry is highly vulnerable to hypoxia-ischemia in the PVL model, thus identifying a novel target site in PVL pathology.

ObjectiveThe proteinaceous inclusions in TDP-43 proteinopathies such as frontotemporal lobar degeneration (FTLD)-TDP are made of high-molecular-weight aggregates of TDP-43. These aggregates have not been classified as amyloids, as prior amyloid staining results were not conclusive. Here we used a specific TDP-43 amyloid oligomer antibody called TDP-O to determine the presence and abundance of TDP-43 oligomers among different subtypes of FTLD-TDP as well as in hippocampal sclerosis (HS), which represents a non-FTLD pathology with TDP-43 inclusions.MethodsPostmortem tissue from the hippocampus and anterior orbital gyrus from 54 prospectively assessed and diagnosed subjects was used for immunostaining with TDP-O. Electron microscopy was used to assess the subcellular locations of TDP-O-decorated structures.ResultsTDP-43 inclusions staining with TDP-O were present in FTLD-TDP and were most conspicuous for FTLD-TDP type C, the subtype seen in most patients with semantic variant primary progressive aphasia. TDP-O immunoreactivity was absent in the hippocampus of HS patients despite abundant TDP-43 inclusions. Ultrastructurally, TDP-43 oligomers resided in granular or tubular structures, frequently in close proximity to, but not within, neuronal lysosomes.InterpretationTDP-43 forms amyloid oligomers in the human brain, which may cause neurotoxicity in a manner similar to other amyloid oligomers. Oligomer formation may contribute to the conformational heterogeneity of TDP-43 aggregates and mark the different properties of TDP-43 inclusions between FTLD-TDP and HS.

Rett syndrome (RTT) is an autism spectrum disorder caused by loss-of-function mutations in the gene encoding MeCP2, an epigenetic modulator that binds the methyl CpG dinucleotide in target genes to regulate transcription. Previously, we and others reported a role of microglia in the pathophysiology of RTT. To understand the mechanism of microglia dysfunction in RTT, we identified a MeCP2 target gene, SLC38A1, which encodes a major glutamine transporter (SNAT1), and characterized its role in microglia. We found that MeCP2 acts as a microglia-specific transcriptional repressor of SNAT1. Because glutamine is mainly metabolized in the mitochondria, where it is used as an energy substrate and a precursor for glutamate production, we hypothesize that SNAT1 overexpression in MeCP2-deficient microglia would impair the glutamine homeostasis, resulting in mitochondrial dysfunction as well as microglial neurotoxicity because of glutamate overproduction. Supporting this hypothesis, we found that MeCP2 downregulation or SNAT1 overexpression in microglia resulted in (1) glutamine-dependent decrease in microglial viability, which was corroborated by reduced microglia counts in the brains of MECP2 knock-out mice; (2) proliferation of mitochondria and enhanced mitochondrial production of reactive oxygen species; (3) increased oxygen consumption but decreased ATP production (an energy-wasting state); and (4) overproduction of glutamate that caused NMDA receptor-dependent neurotoxicity. The abnormalities could be rectified by mitochondria-targeted expression of catalase and a mitochondria-targeted peptide antioxidant, Szeto-Schiller 31. Our results reveal a novel mechanism via which MeCP2 regulates bioenergetic pathways in microglia and suggest a therapeutic potential of mitochondria-targeted antioxidants for RTT.

BackgroundAbnormal connectivity across brain regions underlies many neurological disorders including multiple sclerosis, schizophrenia and autism, possibly due to atypical axonal organization within white matter. Attempts at investigating axonal organization on post-mortem human brains have been hindered by the availability of high-quality, morphologically preserved tissue, particularly for neurodevelopmental disorders such as autism. Brains are generally stored in a fixative for long periods of time (often greater than 10 years) and in many cases, already frozen and sectioned on a microtome for histology and immunohistochemistry. Here we present a method to assess the quality and quantity of axons from long-term fixed and frozen-sectioned human brain samples to demonstrate their use for electron microscopy (EM) measures of axonal ultrastructure.ResultsSix samples were collected from white matter below the superior temporal cortex of three typically developing human brains and prepared for EM analyses. Five samples were stored in fixative for over 10 years, two of which were also flash frozen and sectioned on a freezing microtome, and one additional case was fixed for 3 years and sectioned on a freezing microtome. In all six samples, ultrastructural qualitative and quantitative analyses demonstrate that myelinated axons can be identified and counted on the EM images. Although axon density differed between brains, axonal ultrastructure and density was well preserved and did not differ within cases for fixed and frozen tissue. There was no significant difference between cases in axon myelin sheath thickness (g-ratio) or axon diameter; approximately 70% of axons were in the small (0.25 μm) to medium (0.75 μm) range. Axon diameter and g-ratio were positively correlated, indicating that larger axons may have thinner myelin sheaths.ConclusionThe current study demonstrates that long term formalin fixed and frozen-sectioned human brain tissue can be used for ultrastructural analyses. Axon integrity is well preserved and can be quantified using the methods presented here. The ability to carry out EM on frozen sections allows for investigation of axonal organization in conjunction with other cellular and histological methods, such as immunohistochemistry and stereology, within the same brain and even within the same frozen cut section.

Pluripotent stem cells (PSCs) have been differentiated into oligodendroglial progenitor cells (OPCs), providing promising cell replacement therapies for many central nervous system disorders. Studies from rodents have shown that brain OPCs express a variety of ion channels, and that a subset of brain OPCs express voltage-gated sodium channel (NaV ), mediating the spiking properties of OPCs. However, it is unclear whether PSC-derived OPCs exhibit electrophysiological properties similar to brain OPCs and the role of NaV in the functional maturation of OPCs is unknown. Here, using a mouse embryonic stem cell (mESC) green fluorescent protein (GFP)-Olig2 knockin reporter line, we demonstrated that unlike brain OPCs, all the GFP(+) /Olig2(+) mESC-derived OPCs (mESC-OPCs) did not express functional NaV and failed to generate spikes (hence termed "nonspiking mESC-OPCs"), while expressing the delayed rectifier and inactivating potassium currents. By ectopically expressing NaV 1.2 α subunit via viral transduction, we successfully generated mESC-OPCs with spiking properties (termed "spiking mESC-OPCs"). After transplantation into the spinal cord and brain of myelin-deficient shiverer mice, the spiking mESC-OPCs demonstrated better capability in differentiating into myelin basic protein expressing oligodendrocytes and in myelinating axons in vivo than the nonspiking mESC-OPCs. Thus, by generating spiking and nonspiking mESC-OPCs, this study reveals a novel function of NaV in OPCs in their functional maturation and myelination, and sheds new light on ways to effectively develop PSC-derived OPCs for future clinical applications.

Local production of neurosteroids such as progesterone and allopregnanolone confers neuroprotection in central nervous system (CNS) inflammatory diseases. The mitochondrial translocator protein (TSPO) performs a rate-limiting step in the conversion of cholesterol to pregnenolone and its steroid derivatives. Previous studies have shown that TSPO is upregulated in microglia and astroglia during neural inflammation, and radiolabelled TSPO ligands such as PK11195 have been used to image and localize injury in the CNS. Recent studies have shown that modulating TSPO activity with pharmacological ligands such as etifoxine can initiate the production of neurosteroids locally in the injured CNS. In this study, we examined the effects of etifoxine, a clinically available anxiolytic drug, in the development and progression of mouse experimental autoimmune encephalomyelitis (EAE), an experimental model for multiple sclerosis (MS). Our results showed that etifoxine attenuated EAE severity when administered before the development of clinical signs and also improved symptomatic recovery when administered at the peak of the disease. In both cases, recovery was correlated with diminished inflammatory pathology in the lumbar spinal cord. Modulation of TSPO activity by etifoxine led to less peripheral immune cell infiltration of the spinal cord, and increased oligodendroglial regeneration after inflammatory demyelination in EAE. Our results suggest that a TSPO ligand, e.g. etifoxine, could be a potential new therapeutic option for MS with benefits that could be comparable to the administration of systemic steroids but potentially avoiding the detrimental side effects of long-term direct use of steroids.

BackgroundThe development of the corticospinal tract (CST) in higher vertebrates relies on a series of axon guidance decisions along its long projection pathway. Several guidance molecules are known to be involved at various decision points to regulate the projection of CST axons. However, previous analyses of the CST guidance defects in mutant mice lacking these molecules have suggested that there are other molecules involved in CST axon guidance that are yet to be identified. In this study, we investigate the role of plexin signaling in the guidance of motor CST axons in vivo.ResultsExpression pattern studies show that plexin-A3, plexin-A4, and neuropilin-1 are expressed in the developing cerebral cortex when the motor CST axons originating from layer V cortical neurons are guided down to the spinal cord. By analyzing mutant mice, we show that motor CST axons that turn dorsally to cross the midline at the pyramidal decussation require plexin-A3 and plexin-A4 signaling. Although other CST guidance defects are found in neuropilin-1 mutants, this dorsal turning defect is not observed in either neuropilin-1 or neuropilin-2 mutants, suggesting that the local cues that activate plexin signaling at the dorsal turning point are membrane-bound semaphorins. Further expression pattern study and mutant analysis indicate that Sema6A is one of the local cues for motor CST axon turning at the pyramidal decussation.ConclusionDorsal turning and midline crossing at the pyramidal decussation is a crucial step to properly direct CST axons into the dorsal spinal cord. We show that the signaling of plexin-A3, plexin-A4, and Sema6A is at least partially required for dorsal turning of the CST axons, while neuropilin-1 is required for proper fasciculation of the tract at midline crossing. Together with previous reports, these results demonstrate that several guidance cues are specifically utilized to regulate the dorsal turning and midline crossing of developing CST axons.

Objective To establish a health emergency competency evaluation index system for public health personnel, so as to provide a theoretical basis for building a health emergency team. Methods The competency index was screened and the evaluation index frame was established by literature research method, expert association commercial method and Delphi method. The analytic hierarchy process was used to calculate the weight value of the importance of indicators at all levels, and the evaluation index system was formed. Results A total of 21 experts were invited to conduct letter inquiries, and the recovery rate of the two rounds of expert letter inquiries was 100%. The Cronbach's a coefficients of the expert letter consultation form were 0.968 and 0.963, expert authority level 0.865, Kendall's W coordination coefficient in 2 rounds of correspondence suggested that experts had a high consistency (P < 0.05) . The evaluation index system of public health personnel's competency in health emergency work included 3 first-level indicators, 11 second-level indicators and 68 third-level indicators. The weights of the first-level indicators are respectively health emergency literacy (0.517 4), professional literacy (0.336 1) and personal literacy (0.146 6). Conclusion Good health emergency literacy is the basis for public health personnel to respond to public health emergencies. The weight of each index in this index system is determined by Delphi method and analytic hierarchy process, and the results are scientific and reliable. [ABSTRACT FROM AUTHOR]