Objective To observe the depressive behavior and neuronal damage induced by different doses of corticosterone(CORT)in mice,and to explore the optimal dose for a corticosterone-induced depression model in mice.Methods Forty male C57BL/6J mice were divided randomly into four groups:control group and low,medium,and high CORT groups(20,40,and 60 mg/kg,respectively),treated with the corresponding drug dose by subcutaneous injection for 4 weeks.Behavioral c hanges in mice after corticosterone administration for 3 and 4 weeks were detected by sugar water preference,forced swimming,tail suspension,and open field tests.Morphological changes in neurons in the hippocampal CA1 area and forebrain cortex area were observed by hematoxylin-eosin(HE)and Nissl staining.Serum levels of 5-hydroxytryptamine(5-HT)were detected by enzyme-linked immunosorbent assay.Depression-related behavioral changes induced by different doses of corticosterone were compared.Results The bodyweights of mice in all three CORT groups(20,40,and 60 mg/kg)decreased(P＜0.05)and the preference for sucrose solution decreased(P＜0.01)compared with the findings in the control group.The immobility time in the forced swimming test was prolonged in the CORT 20 and 40 mg/kg groups(P＜0.01)and the immobility time of mice in the tail suspension test was prolonged in the CORT 40 mg/kg group(P＜0.05).The total distance,the length of time spent in the peripheral area was prolonged and the time entering the central area in the open-field experiment were decreased in the CORT 40 and 60 mg/kg groups(P＜0.05),and average speed were decreased in the CORT 40 mg/kg group(P＜0.05).In addition,CORT injection result ed in abnormal neuronal cell morphology,cell deformation,and nuclear condensation in the hippocampal CA1 and forebrain cortex areas,to different degrees.Serum 5-hydroxytryptamine levels were reduced in the CORT 40 and 60 mg/kg groups(P＜0.05).Conclusions CORT 20,40,and 60 mg/kg can induce depression-like behavioral changes and neuronal damage in mice to varying degrees,with the most notable effect at 40 mg/kg.Under experimental conditions,we consider that 40 mg/kg is the best dose for replicating corticosterone-induced depression in model mice.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Critically ill patients often experience significant skeletal muscle wasting due to prolonged bed rest, metabolic disorders, inflammatory responses and malnutrition, which affects the patient's mobility and may also lead to increased mortality. Timely and accurate assessment of muscle status is important for optimizing treatment strategies and improving patient prognosis. There are various limitations in the current methods of assessing muscle mass, and muscle ultrasound, as a noninvasive, convenient, low-cost and suitable technique for bedside monitoring, has received increasing attention for its application in muscle assessment of critically ill patients. However, there are still a number of challenges in its practical application, such as the lack of uniform standards for the measurement method, the high dependence on the operation, and the reproducibility of the data that needs to be optimized, and so on. The aim of this article is to systematize the research progress of muscle ultrasound in muscle assessment of critically ill patients, and to discuss the advantages and limitations of its clinical application, in order to provide a scientific basis for future research and clinical practice.
Humans ; Critical Illness ; Ultrasonography ; Muscle, Skeletal/diagnostic imaging*

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

Aim To investigate the pharmacological mechanism of Ebselenin(Ebselen,EbSe)in the treat-ment of Escherichia coli(E.coli)infection,which had no significant inhibitory effect on Gram-negative bacte-ria,based on previous studies.Methods After EbSe intervention in E.coli infected Raw264.7 cells,the via-bility of Raw264.7 cells was determined by CCK-8 method,the morphology and structure of Raw264.7 cells were observed by electron microscope,and the in-tracellular bacterial load of Raw264.7 cells was calcu-lated by coated plate method.Polarization status of peritoneal macrophages,Raw264.7 intracellular NO and ROS content and intracellular HO-1 expression in Raw264.7 and E.coli acutely infected mice after E.co-li infection by flow cytometry.qPCR was used to detect the expression of related mRNAs in Raw264.7 cells.qPCR was used to detect the intracellular GSH content in Raw264.7 cells by spectrophotometric assay,and the state of cytoskeletal proteins was observed by immuno-fluorescence.Western blot assay was performed to de-tect the intracellular Txnrd1 expression level.Results Microtiter method,CCK-8,and electron microscopy observations showed that EbSe had no effect on the growth of E.coli and Raw264.7 cells in vitro.The re-sults of smear plate counting showed that EbSe reduced the intracellular bacterial load of Raw264.7 in the in-fected group.Flow cytometry results showed that EbSe upregulated the number of M2-type macrophages.The EbSe-treated infected group had reduced intracellular NO and ROS levels and increased GSH levels.The qPCR results showed that the expression of IL-6,IL-1β,and iNOS was decreased,and the expression of HO-1,Txnrd1,and Glut1 was increased in DHB4-in-fected Raw264.7 cells after EbSe treatment.Cytoskel-etal staining showed that the morphology of the EbSe-treated infected cells was similar to that of oxPAPC-in-duced cells.Western blot results showed the expres-sion of Txnrd1 protein in EbSe-treated infected cells in-creased.Conclusion EbSe exerts anti-E.coli acute infection effect by regulating macrophage polarization and inhibiting macrophage excessive inflammatory state.

Objective To observe the depressive behavior and neuronal damage induced by different doses of corticosterone(CORT)in mice,and to explore the optimal dose for a corticosterone-induced depression model in mice.Methods Forty male C57BL/6J mice were divided randomly into four groups:control group and low,medium,and high CORT groups(20,40,and 60 mg/kg,respectively),treated with the corresponding drug dose by subcutaneous injection for 4 weeks.Behavioral c hanges in mice after corticosterone administration for 3 and 4 weeks were detected by sugar water preference,forced swimming,tail suspension,and open field tests.Morphological changes in neurons in the hippocampal CA1 area and forebrain cortex area were observed by hematoxylin-eosin(HE)and Nissl staining.Serum levels of 5-hydroxytryptamine(5-HT)were detected by enzyme-linked immunosorbent assay.Depression-related behavioral changes induced by different doses of corticosterone were compared.Results The bodyweights of mice in all three CORT groups(20,40,and 60 mg/kg)decreased(P＜0.05)and the preference for sucrose solution decreased(P＜0.01)compared with the findings in the control group.The immobility time in the forced swimming test was prolonged in the CORT 20 and 40 mg/kg groups(P＜0.01)and the immobility time of mice in the tail suspension test was prolonged in the CORT 40 mg/kg group(P＜0.05).The total distance,the length of time spent in the peripheral area was prolonged and the time entering the central area in the open-field experiment were decreased in the CORT 40 and 60 mg/kg groups(P＜0.05),and average speed were decreased in the CORT 40 mg/kg group(P＜0.05).In addition,CORT injection result ed in abnormal neuronal cell morphology,cell deformation,and nuclear condensation in the hippocampal CA1 and forebrain cortex areas,to different degrees.Serum 5-hydroxytryptamine levels were reduced in the CORT 40 and 60 mg/kg groups(P＜0.05).Conclusions CORT 20,40,and 60 mg/kg can induce depression-like behavioral changes and neuronal damage in mice to varying degrees,with the most notable effect at 40 mg/kg.Under experimental conditions,we consider that 40 mg/kg is the best dose for replicating corticosterone-induced depression in model mice.

Aim To investigate the pharmacological mechanism of Ebselenin(Ebselen,EbSe)in the treat-ment of Escherichia coli(E.coli)infection,which had no significant inhibitory effect on Gram-negative bacte-ria,based on previous studies.Methods After EbSe intervention in E.coli infected Raw264.7 cells,the via-bility of Raw264.7 cells was determined by CCK-8 method,the morphology and structure of Raw264.7 cells were observed by electron microscope,and the in-tracellular bacterial load of Raw264.7 cells was calcu-lated by coated plate method.Polarization status of peritoneal macrophages,Raw264.7 intracellular NO and ROS content and intracellular HO-1 expression in Raw264.7 and E.coli acutely infected mice after E.co-li infection by flow cytometry.qPCR was used to detect the expression of related mRNAs in Raw264.7 cells.qPCR was used to detect the intracellular GSH content in Raw264.7 cells by spectrophotometric assay,and the state of cytoskeletal proteins was observed by immuno-fluorescence.Western blot assay was performed to de-tect the intracellular Txnrd1 expression level.Results Microtiter method,CCK-8,and electron microscopy observations showed that EbSe had no effect on the growth of E.coli and Raw264.7 cells in vitro.The re-sults of smear plate counting showed that EbSe reduced the intracellular bacterial load of Raw264.7 in the in-fected group.Flow cytometry results showed that EbSe upregulated the number of M2-type macrophages.The EbSe-treated infected group had reduced intracellular NO and ROS levels and increased GSH levels.The qPCR results showed that the expression of IL-6,IL-1β,and iNOS was decreased,and the expression of HO-1,Txnrd1,and Glut1 was increased in DHB4-in-fected Raw264.7 cells after EbSe treatment.Cytoskel-etal staining showed that the morphology of the EbSe-treated infected cells was similar to that of oxPAPC-in-duced cells.Western blot results showed the expres-sion of Txnrd1 protein in EbSe-treated infected cells in-creased.Conclusion EbSe exerts anti-E.coli acute infection effect by regulating macrophage polarization and inhibiting macrophage excessive inflammatory state.

Idiopathic pulmonary fibrosis （IPF）， as a progressive lung disease， has a poor prognosis and no reliable and effective therapies. IPF is mainly treated by organ transplantation and administration of chemical drugs， which are ineffective and induce side effects， failing to meet the clinical needs. Therefore， developing safer and more effective drugs has become an urgent task， which necessitates clear understanding of the pathogenesis of IPF. The available studies about the pathogenesis of IPF mainly focus on macrophage polarization， epithelial-mesenchymal transition （EMT）， oxidative stress， and autophagy， while few studies systematically explain the principles and links of the pathogeneses. According to the traditional Chinese medicine theory， Qi deficiency and blood stasis and Qi-Yang deficiency are the key pathogeneses of IPF. Therefore， the Chinese medicines or compound prescriptions with the effects of replenishing Qi and activating blood， warming Yang and tonifying Qi， and eliminating stasis and resolving phlegm are often used to treat IPF. Modern pharmacological studies have shown that such medicines play a positive role in inhibiting macrophage polarization， restoring redox balance， inhibiting EMT， and regulating cell autophagy. However， few studies report how Chinese medicines regulate the pathways in the treatment of IPF. By reviewing the latest articles in this field， we elaborate on the pathogenesis of IPF and provide a comprehensive overview of the mechanism of the active ingredients or compound prescriptions of Chinese medicines in regulating IPF. Combining the pathogenesis of IPF with the modulating effects of Chinese medicines， we focus on exploring systemic treatment options for IPF， with a view to providing new ideas for the in-depth study of IPF and the research and development of related drugs.

Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived car-diomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a po-tential reagent for repairing damaged hearts.

Traumatic dental injuries(TDIs)of teeth occur frequently in children and adolescents.TDIs that impact the periodontal tissues and alveolar tissue can be classified into concussion,subluxation,extrusive luxation,intrusive luxation,lateral luxation,and avulsion.In these TDIs,management of injured soft tissue,mainly periodontal ligament,and dental pulp,is crucial in maintaining the function and longevity of the injured teeth.Factors that need to be considered for management in laxation injuries include the maturation stage of the traumatic teeth,mobility,direction of displacement,distance of displacement,and whether there are alveolar fractures.In avulsion,the maturation stage of the permanent tooth,the out-socket time,storage media/condition of the avulsed tooth,and management of the PDL should also be considered.Especially,in this review,we have subdivided the immature tooth into the adolescent tooth(Nolla stage 9)and the very young tooth(Nolla stage 8 and below).This consensus paper aimed to discuss the impacts of those factors on the trauma management and prognosis of TDI to provide a streamlined guide for clinicians from clinical evaluation,diagnostic process,management plan decision,follow-up,and orthodontic treatment for tooth luxation and avulsion injuries.