Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective:To analyze the application of antitoxin therapy in severe infant botulism.Methods:A retrospective analysis was conducted on 14 cases of severe infant botulism treated at 3 pediatric medical centers from July 2020 to August 2024. This study investigated antitoxin dosage, treatment duration, discontinuation criteria and adverse reactions.Results:A total of 14 cases (12 males and 2 females) were included, with an age of 5.0 (3.8, 7.0) months. Botulinum toxin typing revealed 10 cases of Type B, 2 cases of Type A and 2 untyped cases. The interval from symptom onset to antitoxin administration was 9.0 (6.0, 11.5) d. The initial dosage of type A antitoxin was 12 500 (10 000, 22 500) U, while type B was 5 000 (5 000, 5 000) U. The dosage was tapered in some cases after symptom improvement, the duration of treatment was 16.5 (9.8, 25.3) d. In total, 11 infants discontinued medications after improvement in muscle strength, while 3 infants discontinued treatment after obtaining negative results from fecal mouse bioassays. Adverse events were reported in 2 cases, both of which resulted in rash, and 1 case was complicated with anaphylactic shock. All the patients survived upon discharge with a follow-up period of 11 d to 3 years and 8 months. Totally 12 infants had fully recovered, while 2 infants were still recovering after discharge.Conclusion:Antitoxin therapy is a feasible and safe approach which showed favorable prognosis in severe infant botulism.

Objective:To analyze the clinical characteristics and nutritional treatment of malnutrition in infants with botulism.Methods:A retrospective analysis was conducted on 25 infant botulism patients admitted to Beijing Children's Hospital Affiliated to Capital Medical University，from May 1，2019 to October 31，2024.The nutritional risk and malnutrition incidence were assessed，nutritional therapy methods，formulations，tolerance status, energy intake rate, secondary infections and prognosis were analyzed.Results:A total of 25 pediatric patients were included, 19 males and 6 females, with a median age of 5(4,6) months. Twenty-five cases (100%) showed reduced food intake, with a weight of 7.3 (7.0, 9.0) kg upon admission. Twenty-four cases (96%) were assessed as high-risk for nutrition screening, and one case was diagnosed with malnutrition. Twenty-four cases (96%) received nasogastric tube feeding, with an early enteral nutrition implementation rate of 84% (21 cases) and intermittent infusion in 25 cases (100%). Fourteen cases used whole protein formula milk,eight cases used hydrolyzed protein formula milk and three cases were given 5% sugar solution. Nine cases were treated with intravenous nutrition, with a duration of 9 (5, 12) days. Five cases (20%) developed enteral feeding intolerance, and all five cases had secondary infections and were treated with parenteral nutrition. All 25 patients had good prognosis. At discharge, 17 cases (68%) were fed orally, and eight cases (32%) were fed through nasogastric tubes, with a median weight of 7.5 (7.0, 9.0) kg. Fifteen patients (60%) had weight gain, and the nutritional screening assessment was all low-risk.Conclusion:Infants with botulism are mostly in a state of high nutritional risk when they are admitted to hospital. Early enteral nutrition through a gastric tube has a high implementation rate. Some children may experience feeding intolerance,combined with timely use of parenteral nutrition replacement and symptomatic treatment can improve prognosis.

Acute necrotizing encephalopathy（ANE）is a rare post-infectious neurological disease primarily affecting children under 5 years old，with a high mortality and disability rate.Early administration of high-dose glucocorticoids is widely recognized as crucial for optimal efficacy of treatment.However，standardized guidance is lacking，and the optimal dosage as well as timing for administration require validation in larger patient populations.Additionally，combination therapies involving intravenous immunoglobulin，plasmapheresis，tocilizumab，and antiviral treatments may enhance efficacy and reduce mortality rates and neurological sequelae.This review summarized the current application status of high-dose glucocorticoid therapy for ANE in recent years and analyzed the differences in efficacy among different types and doses of glucocorticoids,as well as different timing of administration,with the aim of providing valuable references for optimizing treatment regimens in the future.

Acute necrotizing encephalopathy（ANE）is a rare post-infectious neurological disease primarily affecting children under 5 years old，with a high mortality and disability rate.Early administration of high-dose glucocorticoids is widely recognized as crucial for optimal efficacy of treatment.However，standardized guidance is lacking，and the optimal dosage as well as timing for administration require validation in larger patient populations.Additionally，combination therapies involving intravenous immunoglobulin，plasmapheresis，tocilizumab，and antiviral treatments may enhance efficacy and reduce mortality rates and neurological sequelae.This review summarized the current application status of high-dose glucocorticoid therapy for ANE in recent years and analyzed the differences in efficacy among different types and doses of glucocorticoids,as well as different timing of administration,with the aim of providing valuable references for optimizing treatment regimens in the future.

Objective:To analyze the clinical characteristics and nutritional treatment of malnutrition in infants with botulism.Methods:A retrospective analysis was conducted on 25 infant botulism patients admitted to Beijing Children's Hospital Affiliated to Capital Medical University，from May 1，2019 to October 31，2024.The nutritional risk and malnutrition incidence were assessed，nutritional therapy methods，formulations，tolerance status, energy intake rate, secondary infections and prognosis were analyzed.Results:A total of 25 pediatric patients were included, 19 males and 6 females, with a median age of 5(4,6) months. Twenty-five cases (100%) showed reduced food intake, with a weight of 7.3 (7.0, 9.0) kg upon admission. Twenty-four cases (96%) were assessed as high-risk for nutrition screening, and one case was diagnosed with malnutrition. Twenty-four cases (96%) received nasogastric tube feeding, with an early enteral nutrition implementation rate of 84% (21 cases) and intermittent infusion in 25 cases (100%). Fourteen cases used whole protein formula milk,eight cases used hydrolyzed protein formula milk and three cases were given 5% sugar solution. Nine cases were treated with intravenous nutrition, with a duration of 9 (5, 12) days. Five cases (20%) developed enteral feeding intolerance, and all five cases had secondary infections and were treated with parenteral nutrition. All 25 patients had good prognosis. At discharge, 17 cases (68%) were fed orally, and eight cases (32%) were fed through nasogastric tubes, with a median weight of 7.5 (7.0, 9.0) kg. Fifteen patients (60%) had weight gain, and the nutritional screening assessment was all low-risk.Conclusion:Infants with botulism are mostly in a state of high nutritional risk when they are admitted to hospital. Early enteral nutrition through a gastric tube has a high implementation rate. Some children may experience feeding intolerance,combined with timely use of parenteral nutrition replacement and symptomatic treatment can improve prognosis.

Objective:To analyze the application of antitoxin therapy in severe infant botulism.Methods:A retrospective analysis was conducted on 14 cases of severe infant botulism treated at 3 pediatric medical centers from July 2020 to August 2024. This study investigated antitoxin dosage, treatment duration, discontinuation criteria and adverse reactions.Results:A total of 14 cases (12 males and 2 females) were included, with an age of 5.0 (3.8, 7.0) months. Botulinum toxin typing revealed 10 cases of Type B, 2 cases of Type A and 2 untyped cases. The interval from symptom onset to antitoxin administration was 9.0 (6.0, 11.5) d. The initial dosage of type A antitoxin was 12 500 (10 000, 22 500) U, while type B was 5 000 (5 000, 5 000) U. The dosage was tapered in some cases after symptom improvement, the duration of treatment was 16.5 (9.8, 25.3) d. In total, 11 infants discontinued medications after improvement in muscle strength, while 3 infants discontinued treatment after obtaining negative results from fecal mouse bioassays. Adverse events were reported in 2 cases, both of which resulted in rash, and 1 case was complicated with anaphylactic shock. All the patients survived upon discharge with a follow-up period of 11 d to 3 years and 8 months. Totally 12 infants had fully recovered, while 2 infants were still recovering after discharge.Conclusion:Antitoxin therapy is a feasible and safe approach which showed favorable prognosis in severe infant botulism.

Objectives:To retrieve,evaluate and summarize the contemporary evidence of strategies for weaning from extracorporeal membrane oxygenation(ECMO)of adult patients,and to provide evidence-based reference for clinical practice. Methods:The Web of Science,Embase,Cochrane Library,PubMed,Wanfang Database,CNKI,VIP website,SinoMed,BMJ Best Practice,National Institute for Health and Care Excellence,Joanna Briggs Institute Library,UpToDate and the website of Agency for Healthcare Research and Quality,Society of Critical Care Medicine,American Association of Critical-Care Nurses,European Society of Intensive Care Medicine and Extracorporeal Life Support Organization were researched to collect the literature related to randomized controlled trials,systematic reviews,guidelines,evidence summaries,expert consensuses and clinical decisions in this field.The time limit for the retrieval is from the inception of databases until July 2023. Results:A total of 13 related literature were retrieved,including 4 guidelines,4 expert consensuses,3 clinical decisions and 2 system reviews.Totally 42 evidences were formulated based on retrieved literature,including adequately accessing the ability of gas exchange before weaning from veno-venous ECMO(V-V ECMO)and withdrawing from veno-arterial ECMO(V-A ECMO)as soon as possible when patients's heart function has recovered,involving six aspects such as team composition,anticoagulation measures,assessment before weaning,weaning implementation,cannula and wound management and quality measures. Conclusions:It is suggested to build a professional ECMO team based on the actual hospital situation,to follow the contemporary evidence to standardize the weaning process of patients from ECMO to ensure the patients'safety and improve the outcomes.

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

Objective:To summarize the clinical characteristics and prognosis of severe infant botulism and evaluate the therapeutic effect of botulinum antitoxin in the pediatric intensive care unit (PICU).Methods:The clinical data of 8 cases diagnosed with infantile botulism were retrospectively analyzed in the PICU of Beijing Children′s Hospital from October 2019 to August 2023. Data of basic demographic information, clinical manifestations, laboratory tests, treatment and prognosis of each child were collected and analyzed using descriptive statistical methods.Results:Eight laboratory-confirmed cases of infant botulism were included in this study, all of which were male infants with an age of 6.0 (3.3,6.8) months. Three of the children were from Inner Mongolia Autonomous Region, 2 of them were from Hebei, and the other 3 were from Beijing, Shandong and Xinjiang Uyghur Autonomous Region, respectively. All the patients were previously healthy. In 4 of these cases, the possible cause was the ingestion of either honey and its products or sealed pickled food by the mother or child before the onset of the disease. The first symptom was poor milk intake (4 cases), followed by shallow shortness of breath (7 cases), limb weakness (7 cases) and so on. The typical signs were bilateral dilated pupils (8 cases) and decreased limb muscle strength (8 cases). The main subtype was type B (7 cases), and only 1 case was classified as type A. Six of the children were treated with antitoxin therapy for a duration of 24 (19, 49) d. Seven of them had invasive mechanical ventilation. All the patients survived upon discharge with a follow-up period of 29 d to 3 years and 8 months. Six patients had fully recovered, and 2 recently discharged patients were gradually recovering.Conclusions:For infants with suspected contact or ingestion of botulinum and presented with bilateral pupillary paralysis, muscle weakness and clear consciousness, the stool should be collected for diagnostic testing using a mouse bioassay as soon as possible. Type B was the most common type. The antitoxin treatment was effectiveness and the prognosis was well.