ObjectiveTo evaluate the effect of Suanzaoren Tang on the rat model of depression established by solitary culture combined with chronic unpredictable mild stress by reshaping the inflammatory microenvironment and mediating changes in hippocampal synaptic plasticity. MethodsSeventy-two male SD rats were randomized by a random number table into six groups： control group， model group， fluoxetine group （0.003 6 g·kg^-1）， and high-（10 g·kg^-1）， medium-（5 g·kg^-1）， low-dose （2.5 g·kg^-1）Suanzaoren Tang groups， with 12 rats per group. The sucrose preference rate and open field test scores of rats in each group were observed. Western blot was employed to determine the expression levels of the key proteins in the specificity protein 1 （SP1）/sphingosine kinase 1 （SK1）/sphingosine-1-phosphate receptor 1 （S1PR1） signaling pathway， as well as hippocampal proteins synaptophysin Ⅰ （SYNⅠ）， postsynaptic density protein-95 （PSD-95）， and family with sequence similarity 19， member A5 （FAM19A5）. Immunohistochemistry was employed to detect the positive expression of SP1， PSD-95， SYNⅠ， interleukin （IL）-10， and IL-6. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of SP1 and S1PR1. Finally， transmission electron microscopy was employed to observe the ultrastructural changes of hippocampal synapses. ResultsCompared with the control group， the model group exhibited a decrease in sucrose preference index （P<0.01） and reduced total scores for horizontal and vertical movements in the open field test （P<0.01）， which indicated the successful modeling of depression. Moreover， the model group showed reduced synaptic vesicles in the hippocampus （P<0.01）， up-regulated expression of SP1， SK1， S1PR1， and IL-6 （P<0.01）， and down-regulated expression of SYNⅠ， PSD-95， FAM19A5， and IL-10 （P<0.01）. Compared with the model group， high- and medium-dose Suanzaoren Tang and fluoxetine increased the sucrose preference index and the total scores for horizontal and vertical movements in the open field test （P<0.01）. All Suanzaoren Tang groups and the fluoxetine group demonstrated reductions in SP1， SK1， S1PR1， and IL-6 expression （P<0.05， P<0.01）， alongside restored synaptic vesicles in the hippocampus （P<0.05， P<0.01）. ConclusionSuanzaoren Tang modulates hippocampal expression of FAM19A5， SYNⅠ， PSD-95， IL-10， IL-6， and the SP1/SK1/S1PR1 pathway in the rat model of depression. The antidepressant effects may be related to the ability of reducing neuroinflammation and enhancing synaptic plasticity.

ObjectiveTo evaluate the effect of Suanzaoren Tang on the rat model of depression established by solitary culture combined with chronic unpredictable mild stress by reshaping the inflammatory microenvironment and mediating changes in hippocampal synaptic plasticity. MethodsSeventy-two male SD rats were randomized by a random number table into six groups： control group， model group， fluoxetine group （0.003 6 g·kg^-1）， and high-（10 g·kg^-1）， medium-（5 g·kg^-1）， low-dose （2.5 g·kg^-1）Suanzaoren Tang groups， with 12 rats per group. The sucrose preference rate and open field test scores of rats in each group were observed. Western blot was employed to determine the expression levels of the key proteins in the specificity protein 1 （SP1）/sphingosine kinase 1 （SK1）/sphingosine-1-phosphate receptor 1 （S1PR1） signaling pathway， as well as hippocampal proteins synaptophysin Ⅰ （SYNⅠ）， postsynaptic density protein-95 （PSD-95）， and family with sequence similarity 19， member A5 （FAM19A5）. Immunohistochemistry was employed to detect the positive expression of SP1， PSD-95， SYNⅠ， interleukin （IL）-10， and IL-6. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of SP1 and S1PR1. Finally， transmission electron microscopy was employed to observe the ultrastructural changes of hippocampal synapses. ResultsCompared with the control group， the model group exhibited a decrease in sucrose preference index （P<0.01） and reduced total scores for horizontal and vertical movements in the open field test （P<0.01）， which indicated the successful modeling of depression. Moreover， the model group showed reduced synaptic vesicles in the hippocampus （P<0.01）， up-regulated expression of SP1， SK1， S1PR1， and IL-6 （P<0.01）， and down-regulated expression of SYNⅠ， PSD-95， FAM19A5， and IL-10 （P<0.01）. Compared with the model group， high- and medium-dose Suanzaoren Tang and fluoxetine increased the sucrose preference index and the total scores for horizontal and vertical movements in the open field test （P<0.01）. All Suanzaoren Tang groups and the fluoxetine group demonstrated reductions in SP1， SK1， S1PR1， and IL-6 expression （P<0.05， P<0.01）， alongside restored synaptic vesicles in the hippocampus （P<0.05， P<0.01）. ConclusionSuanzaoren Tang modulates hippocampal expression of FAM19A5， SYNⅠ， PSD-95， IL-10， IL-6， and the SP1/SK1/S1PR1 pathway in the rat model of depression. The antidepressant effects may be related to the ability of reducing neuroinflammation and enhancing synaptic plasticity.

Objective To analyze the distribution of platelet antibodies in hospitalized patients and explore the clinical significance of platelet antibody detection. Methods A total of 95 987 hospitalized patient cases from a tertiary hospital in Xi'an from April 1, 2021 to December 31, 2023 were collected. Platelet antibodies were detected by solid-phase agglutination method. Statistical analysis was performed on variables including gender, age, blood type, department, history of blood transfusion, pregnancy history, and disease type. Results Among 95 987 hospitalized patients, the positive rate of platelet antibody detection reached 4.35%. The positive rate of platelet antibodies in female hospitalized patients (5.29%) was higher than that in male patients (3.31%), and the difference was statistically significant (x²=224.124). The positive rate of platelet antibodies in those with pregnancy history (7.92%) was higher than that in those without pregnancy history (4.19%), and the difference was significant (x²=292.773). Similarly, the positive rate of platelet antibodies in those with transfusion history (7.79%) was higher than that in those without transfusion history (3.97%), and the difference was significant (x²=300.209). There was a significant correlation between the positive rate of platelet antibodies and the number of pregnancies (x²=91.061). Conclusion The positive rate of platelet antibodies in 95 987 inpatient cases was 4.35%. The positive rate of platelet antibodies had a close relationship with a history of blood transfusions and pregnancies, and it increased with the number of pregnancies. For patients with multiple transfusion histories and pregnancy histories, screening for platelet antibodies holds significant diagnostic value.
Humans ; Female ; Male ; Adult ; Middle Aged ; Blood Platelets/immunology* ; Inpatients ; Aged ; Pregnancy ; Young Adult ; Adolescent ; Aged, 80 and over ; Autoantibodies/blood*

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.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Objective To develop an expert consensus on subcutaneous injection for allergen-specific immunotherapy.Methods Relevant domestic and intemational literature was reviewed,and nursing experts who had experiences in subcutaneous injection of allergen-specific immunotherapy were interviewed to form the initial draft of the consensus.A total of 85 experts from 42 hospitals nationwide were invited to participate in discussions.2 rounds of expert consultations,adjustments,revisions,and improvements were made to the initial draft,and an online meeting was held to form the final version of the consensus.The content approved by more than 75％of the expert group is adopted,or it will be discussed or deleted.Results The expert consensus includes operational standards for subcutaneous injection of allergen-specific immunotherapy,identification and management of adverse reactions,and health education.Conclusion The consensus demonstrates strong scientific rigor and practicality,providing guidance for nursing practices in the field of clinical allergology.

With the advancement of synthetic biology, recombinant proteins are poised to play a significant role in medical applications. The scaled manufacturing is a pillar for the extensive application and development of recombinant proteins across various fields. In the large-scale production process of recombinant proteins, the removal and detection of endotoxins are essential to reduce their levels to safe thresholds in the final products. Currently, establishing stringent endotoxin limits for different recombinant protein products is a crucial aspect of safety assessment. This review begins by shedding light on the pathogenicity of endotoxins and discusses the methods for the removal and determination of endotoxins during the production processes of recombinant proteins. Subsequently, this review summarizes the endotoxin limits in industries such as biologics, medical devices, and human recombinant DNA products, particularly those in recombinant protein injection products. It is highlighted that regardless of whether the hosts for recombinant protein expression are bacteria or not, endotoxin testing is required for the final products of injectable recombinant proteins, and compliance with relevant industry standards is necessary. This review aims to provide a reference for the research on endotoxins in the large-scale production process of recombinant proteins.
Endotoxins/genetics* ; Recombinant Proteins/genetics* ; Humans ; Drug Contamination/prevention & control*

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Objective:To analyze the application effect of cluster management measures in improving the quality of emergency medical treatment.Methods:By analyzing the problems existing in the work of emergency department, the cluster management scheme was formulated and the intervention measures were implemented from the aspects of intelligent information system, patient management system and medical service process. The accuracy and efficiency of emergency triage, the satisfaction of patients and medical staff, the incidence of medical complaints and disputes and the rate of sudden death were compared before and after cluster management.Results:Before and after the implementation of cluster management, the accuracy of triage classification was 95.0% and 98.7% respectively, and the triage time was (68.3±12.8) s and (50.5±7.2) s respectively( P<0.001). The satisfaction of patients, doctors and nurses increased, the number of complaints decreased from 15 to 5 in half a year, and the number of sudden death decreased from 39 to 23 with a significant difference( P<0.05). Conclusions:The application of cluster management measures in emergency management can improve the medical quality, the satisfaction of medical staff and patients, and ensure the safety of patients.

Objective:Resorption can occur after lumbar disc herniation, and Thymic stromal lymphopoietin (TSLP) is considered to be a key factor mediating reabsorption. Studies have found that under the action of inflammatory factors like TNF-α, IL-6, etc,the expression of TSLP in intervertebral disc tissue was increased, and then mononuclear macrophage chemokine-1 (MCP-1) was induced to induce infiltration of macrophage to promote reabsorption. To determine the mechanism, we design the experiment to explore the mechanism of IL-6-mediated JAK/STAT pathway and TGF-β/Smad pathway to promote the reabsorption of intervertebral disc by regulating the expression of TSLP.Methods:Rat bone marrow mesenchymal stem cells (MSC) and rat nucleus pulposus cells (NPC) were cultured in vitro, treating the cells withrat IL-6 recombinant protein, STAT3inhibitor and Smad2/3 inhibitorrespectively, and use real-time quantitative PCR (qRT-PCR) technology to detect the expression of JAK1, STAT3, Smad2, TSLP mRNA under different conditions; Western blot to detect the expression of TSLP, Smad2 and phosphate STAT3 protein; using enzyme-linked immunosorbent assay (Elisa) to detect the expression of TGF-β in two rat cells under the treatment of IL-6.Results:After stimulation ofIL-6 (10 ng/ml or 100 ng/ml) the expression of JAK1in MSC (10 ng/ml: 5.13±1.21; 100 ng/ml: 5.23±0.35; control group: 0.97±0.03), STAT3 (10 ng/ml: 6.50±0.38; 100 ng/ml: 6.74±0.61; control group: 0.87±0.19) was significantly increased, and TSLP also showed high expression in MSC (10 ng/ml: 4.26±0.38; 100 ng/ml: 5.05±0.46; control group: 1.04±0.04).The expression of STAT3 (10 ng/ml: 2.91±0.08; control group: 1.12±0.11), TSLP (10 ng/ml: 7.32±0.37; control group: 1.03±0.03) in NPC also increased. After stimulation of IL-6, the expression of Smad2 increasing in MSC was observed (10 ng/ml: 15.92±0.62; 100 ng/ml: 20.28±0.58; control group: 0.96±0.08), and increased expression of Smad2 in NPC (10 ng/ml: 5.01±0.17; control group: 0.96±0.03). The expression of TSLP in MSC decreased after adding STAT3 inhibitor (BP group, BP group: 0.17±0.01; control group: 0.90±0.09), the expression of TSLP also decreased in NPC (BP group: 0.42±0.11; control group: 0.90±0.11). After adding Smad2/3 inhibitor (SB group), the expression of TSLP in MSC decreased (SB group: 0.33±0.01; control group: 1.02±0.02), and the expression of TSLP in NPC also decreased (SB group: 0.40±0.04; control group: 0.99±0.01).Conclusion:IL-6 up-regulates TSLP expression via the JAK1/STAT3 signaling pathway and promotes prominent intervertebral disc reabsorption. At the same time, IL-6 can activate the TGF-β/Smad2/3 pathway and up-regulate the expression of TSLP, which play a synergistic role in the reabsorption process.