Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective: To understand the influence of the concept of movement education on the fundamental motor skills of preschool children aged 3-6, so as to provide a reference for improving the quality of preschool education and promoting the all round development of preschool children. Methods: From August 2022 to June 2023, 592 normally developing preschool children aged 3- 6 in a certain kindergarten in Qingdao were selected as the research objects by convenience sampling. They were randomly divided into the intervention group (physical education activities designed based on the concept of movement education) and the control group (original teaching plan). The intervention lasted for 24 weeks (twice a week, 40 minutes each time). Test of Gross Motor Development-2 (TGMD-2) was used to evaluate the children s gross motor skills, and repeated measures analysis of variance was used to analyze the data of the two groups before and after the intervention. Results: Except for running and kicking, the group main effects ( F group =18.78-104.77), time main effects( F time =243.23-3 003.19), and other interactive effects between group and time ( F group×time =14.01-322.91) were of statistical significances for gross motor, movement motor, manipulative motor and each sub indicator between intervention group and control group. Further simple effect analysis results showed that, before intervention, there were no statistically significant differences in the total scores of gross motor (48.95±10.65,45.87±10.98), movement motor ( 25.93± 7.31,23.46±7.32) and manipulative motor (23.15±4.40,22.40±4.69) between the intervention group and the control group ( F=3.69, 2.94, 1.90, P >0.05); and two goups were also found of no statistical significance in the each sub indicator of movement and manipulative motor ( F=0.01-3.58, P >0.05); after intervention, the total scores of gross motor, movement motor, and manipulative motor in the intervention group (75.92±9.48, 38.12±5.40, 37.80±4.92) were all better than those in the control group ( 59.52± 12.12, 30.71±7.47, 28.81±5.54) ( F =168.15, 97.58, 210.71), and the total indicators of both goups had better scores than those before the intervention ( F intervention = 3 498.90 , 1 438.27, 2 431.24; F control =545.58, 309.18, 283.29)(all P <0.01); after intervention, the intervention group had better scores in all sub indicators (except for running and kicking) than the control group ( F =43.57-297.71), and the each sub indicator of both goups had better scores than those before the intervention ( F intervention = 300.58-858.65; F control =12.28-135.64)(all P <0.01). Conclusion Physical education activities designed based on the concept of movement education could better promote the development of children s fundamental motor skills.

ObjectiveTo evaluate the quality of Lygodium japonicum (Thunb.) Sw. (L. japonicum, Hai Jin Sha) by comparing its components without stewed (W) and stewed (S) using ultra-high-performance liquid chromatography (UHPLC) and chemometric analysis. Additionally, network pharmacology was employed to investigate the possible mechanisms of action of L. japonicum in the urinary calculi (UC) treatment.MethodsA fingerprinting method was established to identify components through UHPLC-tandem mass spectrometry. Chemometric techniques were used to compare the L. japonicum extraction methods. Furthermore, various network pharmacological approaches were used to identify and analyze the potential targets of the identified components in relation to UC.ResultsThe W and S extracts were distributed into two distinct clusters. Significant differences in the levels of protocatechuic aldehyde, caffeic acid, and p-coumaric acid were observed between S and W. Network pharmacology analysis revealed that the primary targets of L. japonicum in the UC treatment were serum albumin and epidermal growth factor receptors, with potential active components including protocatechuic acid and caffeic acid.ConclusionThis study comprehensively examined the therapeutic components of L. japonicum before and after boiling, shedding light on its potential mechanisms of action in UC treatment. These findings offer valuable insights into the development and utilization of L. japonicum resources.

Objective To explore the efficacy of hypofractionated radiotherapy at different time intervals after surgery for keloid,and to analyze the factors affecting the efficacy.Methods A total of 76 patients who underwent 20 Gy/5 postoperative radiotherapy regimen in the Fifth Affiliated Hospital of Zhengzhou University from January 2021 to June 2023 were selected as study subjects,and a total of 100 keloids were divided into effective group(n=79)and recurrence group(n=21).Regular follow-up and record of the patients after radiotherapy treatment effect and adverse effects,and multivariate Logistic was used to analyze factors of recurrence in keloid patients.Results Multivariate Logistic regression analysis found that postoperative radiotherapy time and scar incision length were related to recurrence after treatment,radiotherapy within 7h of surgery was an independent risk factor for recurrence after treatment(OR＞1,P=0.022),and scar incision≤5cm was an independent protective factor for recurrence after treatment(OR＜1,P=0.028).Conclusion Surgical excision combined with hypofractionated radiotherapy is one of the effective measures to prevent and treat keloid recurrence,though keloids on the trunk may need more effective treatment options.The recurrence rate of radiotherapy initiated 7-48h after surgery is relatively the lowest,and it is worthy of clinical promotion and application.

Objective:To determine the reference interval of IL-10 level in cerebrospinal fluid of adults using multiplex bead-based flow fluorescent immunoassay(MBFFI).Methods:A total of 743 patients without tumor were involved and grouped by diagno-sis.Cerebrospinal fluid and plasma IL-10 were tested by MBFFI.Results:①Cerebrospinal fluid IL-10 levels of the central nervous system infection group were higher than those of other groups.②The cranial venous sinus thrombosis(CVST)group without tumor,in-fection or inflammatory disease were chosen as nearly normal population.As the distribution of cerebrospinal fluid IL-10 levels in these 250 CVST patients were skewed,95％cut-off level was chosen as upper limit and cerebrospinal fluid IL-10<3.50 pg/ml was the refer-ence interval.③No correlation was found between plasma and cerebrospinal fluid IL-10 levels in the CVST group.Conclusion:The medical reference interval of cerebrospinal fluid IL-10 by MBFFI in adults are determined in this study,that is<3.50 pg/ml,to pro-vide clinical reference for practical applications.

Objective:To determine the reference interval of IL-10 level in cerebrospinal fluid of adults using multiplex bead-based flow fluorescent immunoassay(MBFFI).Methods:A total of 743 patients without tumor were involved and grouped by diagno-sis.Cerebrospinal fluid and plasma IL-10 were tested by MBFFI.Results:①Cerebrospinal fluid IL-10 levels of the central nervous system infection group were higher than those of other groups.②The cranial venous sinus thrombosis(CVST)group without tumor,in-fection or inflammatory disease were chosen as nearly normal population.As the distribution of cerebrospinal fluid IL-10 levels in these 250 CVST patients were skewed,95％cut-off level was chosen as upper limit and cerebrospinal fluid IL-10<3.50 pg/ml was the refer-ence interval.③No correlation was found between plasma and cerebrospinal fluid IL-10 levels in the CVST group.Conclusion:The medical reference interval of cerebrospinal fluid IL-10 by MBFFI in adults are determined in this study,that is<3.50 pg/ml,to pro-vide clinical reference for practical applications.

Objective To explore the efficacy of hypofractionated radiotherapy at different time intervals after surgery for keloid,and to analyze the factors affecting the efficacy.Methods A total of 76 patients who underwent 20 Gy/5 postoperative radiotherapy regimen in the Fifth Affiliated Hospital of Zhengzhou University from January 2021 to June 2023 were selected as study subjects,and a total of 100 keloids were divided into effective group(n=79)and recurrence group(n=21).Regular follow-up and record of the patients after radiotherapy treatment effect and adverse effects,and multivariate Logistic was used to analyze factors of recurrence in keloid patients.Results Multivariate Logistic regression analysis found that postoperative radiotherapy time and scar incision length were related to recurrence after treatment,radiotherapy within 7h of surgery was an independent risk factor for recurrence after treatment(OR＞1,P=0.022),and scar incision≤5cm was an independent protective factor for recurrence after treatment(OR＜1,P=0.028).Conclusion Surgical excision combined with hypofractionated radiotherapy is one of the effective measures to prevent and treat keloid recurrence,though keloids on the trunk may need more effective treatment options.The recurrence rate of radiotherapy initiated 7-48h after surgery is relatively the lowest,and it is worthy of clinical promotion and application.

[Objective] In view of the crucial role of indole propionic acid in the treatment of tumor immune checkpoint blockade and further revealing its mechanism, our study intended to design and synthesize 1-[¹⁸F]-fluoroethyl-indole propionic acid (1-[¹⁸F]-IPA), and evaluate it as a tumor PET imaging agent. [Methods] The precursor 1-(2-p-toluenesulfonic acid oxygen ethyl)-methyl indole propionate underwent nucleophilic substitution reaction with ¹⁸F^-. The crude product was separated and purified by high-performance liquid chromatography and the intermediates were collected. Finally, 1-[¹⁸F]-IPA was obtained by hydrolysis. The clarity of the product was measured by visual inspection, the pH value was determined by precision test paper, and the radiochemical purity and stability were determined by high-performance liquid chromatography. In order to determine the biodistribution of 1-[¹⁸F]-IPA in normal mice, ICR mice were intravenously injected with 1-[¹⁸F]-IPA (0.2 mL, 7 MBq), and sacrificed at 5, 15, 25, 45, 75 and 120 min and dissected. Micro-PET imaging was performed and analyzed in BxPC-3 tumor-bearing nude mice. Student t test was used to compare the biodistribution of tissues and organs at different time points. [Results] The total preparation time of 1-[¹⁸F]-IPA was 35-40 min, the radiochemical yield was (45±5)%, and the radiochemical purity was more than 95%. The product solution was clear without particles, and the pH value was 6.5, which had good stability in vitro and in vivo. The results of biodistribution in healthy ICR mice showed that except for the brain, 1-[¹⁸F]-IPA had a certain uptake in all major organs, with the most obvious uptake in the liver, gallbladder and kidneys. The radioactivity in the gallbladder gradually increased with time and reached (39.86±6.56)%ID/g at 120 min, but bone uptake did not change significantly with time. Micro-PET/CT showed that there was radioactive uptake at the tumor 30 min after injection of 1-[¹⁸F]-IPA in Dutch BxPC-3 nude mice, but it was not obvious. At this time, SUVmax was about 55.18±14.62. Consistent with the results of biodistribution, the brain uptake was low at each time point. [Conclusion] In summary, 1-[¹⁸F]-IPA with short preparation time and high yield is expected to be a tool to probe tryptophan indole metabolism pathway and further reveal tumor immune resistance.

One patient with gallbladder mass had transient jaundice and was diagnosed with gallbladder carcinoma by abdominal ultrasonography， contrast-enhanced CT， MRCP， and PET-CT. Surgical exploration showed enlarged gallbladder and a mass in the neck of the gallbladder pressing against the hilum of the liver， with no manifestation of tumor invasion， and there were no signs of liver metastasis. Only cholecystectomy was performed for the patient. The pathological diagnosis was tubular adenoma of the gallbladder without carcinogenesis. This case is characterized by a large gallbladder tumor， without marginal infiltration on imaging or malignant transformation based on pathology.

Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.