ObjectiveTo establish a new noninvasive， simple， and convenient clinical predictive model by identifying independent predictive factors for rebleeding after endoscopic therapy in cirrhotic patients with esophagogastric variceal bleeding （EGVB）， and to provide a basis for individualized risk assessment and development of clinical intervention strategies. MethodsCirrhotic patients with EGVB who were diagnosed and treated in The First Affiliated Hospital of Xi’an Medical University from September 2018 to October 2023 were enrolled as subjects， and according to whether the patient experienced rebleeding within 1 year after endoscopic therapy， they were divided into rebleeding group with 93 patients and non-rebleeding group with 84 patients. Clinical data were collected and analyzed. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. A Logistic model was established based on the results of the univariate and multivariate analyses， and the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to assess the accuracy of the model. R software was used to visualize the model by plotting a nomogram， and the Bootstrap method was used for internal validation of the model. ResultsThe multivariate analysis showed that red blood cell count （RBC）， cholinesterase （ChE）， alkaline phosphatase （ALP）， albumin （Alb）， thrombin time （TT）， portal vein trunk diameter， sequential therapy， and primary prevention were independent predictive factors for rebleeding. Based on the results of the multivariate analysis， a logistic model was established as logit（P）=-0.805-1.978×（RBC）+0.001×（ChE）-0.020×（ALP）-0.314×（Alb）+0.567×（TT）+0.428×（portal vein trunk diameter）-2.303×［sequential therapy （yes=1， no=0）］-2.368×［primary prevention （yes=1， no=0）］. The logistic model （AUC=0.928， 95% confidence interval ［CI］： 0.893—0.964， P<0.001） had a better performance in predicting rebleeding than MELD score （AUC=0.603， 95%CI： 0.520—0.687， P=0.003）， Child-Pugh class （AUC=0.650， 95%CI： 0.578—0.722， P=0.001）， and FIB-4 index （AUC=0.587， 95%CI： 0.503—0.671， P=0.045）. The model had an optimal cut-off value of 0.607， a sensitivity of 0.817， and a specificity of 0.817. Internal validation confirmed that the model had good predictive performance and accuracy. ConclusionSequential therapy， implementation of primary prevention， an increase in RBC， and an increase in Alb are protective factors against rebleeding， while prolonged TT and widened main portal vein diameter are risk factors. The logistic model based on these independent predictive factors can predict rebleeding and thus holds promise for clinical application.

Deutetrabenazine(DTBZ)is a selective oral small molecule inhibitor of vesicular monoamine transporter 2(VMAT2).Its pharmacological action works by inhibiting VMAT2,thereby reducing the release of presynaptic dopamine and alleviating tardive dyskinesia symptoms caused by long-term use of dopamine receptor antagonists.Compared with tetrabenazine,DTBZ has longer half-life,lower peak plasma concentration,and smaller plasma concentration fluctuations.Clinical studies demonstrate that DTBZ significantly improves abnormal involuntary movement in patients with tardive dyskinesia and has a favourable safety profile.Based on available clinical evidence and practical experience,this paper discuss the common questions about DTBZ including the suitable population,dose,duration of treatment,combination administration with antipsychotics,efficacy assessment and application in special populations.This article aimed to provide guidance and recommendations on clinical application of DTBZ for clinicians.

Objective:To explore the application effect of high-fidelity intelligent simulator combined with scenario simulation for emergency response training in the Department of Radiology, and to improve the emergency preparedness of medical, nursing, and technical staff in managing contrast agent adverse reactions.Methods:From January to July 2024, 132 medical, nursing, and technical staff from the Department of Radiology of a tertiary hospital in Chengdu City, China were selected as the training subjects. The high-fidelity intelligent simulator combined with scenario simulation teaching mode was used to conduct emergency response training for the participants. The differences in theoretical knowledge and post competence regarding contrast agent adverse reactions among the staff were compared before and after the training. A self-made questionnaire was used to investigate their needs and satisfaction of the emergency response training. SPSS 26.0 was used for data analysis. The differences in theoretical knowledge and post competence scores before and after training were compared using the paired samples t test. Results:After the training, the average score of theoretical knowledge examination increased from (84.32±10.19) points to (90.34±7.87) points, and the difference was statistically significant ( P<0.001). After the training, the scores of knowledge reserve, operational skills, situational decision-making ability, professional literacy, comprehensive literacy, and overall post competency were all significantly higher than those before the training ( P<0.05). The satisfaction score of emergency response training was (4.17±0.25) points. Conclusions:High-fidelity intelligent simulator combined with scenario simulation training improved the emergency preparedness and teamwork of radiology staff in clinical emergencies. The training received high recognition and satisfaction from the participants, which is of great significance for clinical emergency response and patient safety.

This study elaborates on the teaching reform of the "Five-year Traditional Chinese Medicine Talent Training Program for Traditional Chinese Medicine (Orthopedics Direction)" implemented by Department of Orthopedics in Guangzhou University of Chinese Medicine, including curriculum reform (restructuring courses, emphasizing Lingnan characteristics, and combining medical sciences with martial arts) and teaching model reform (increasing mentorship and learning from teachers, arranging one mentor for every two students, and assigning one teaching team leader for every 5-6 groups). A questionnaire survey conducted among the students of the classes 2022 and 2023 in the five-year TCM talent training program for traditional Chinese medicine (TCM) majors (orthopedics direction) showed that 86.25% (69/80) of the students were satisfied with the mentorship model of "arranging one mentor for every two students", and 87.50% (70/80) of the students agreed that "the assignment of a teaching team leader can help to control teaching intensity". In terms of restructuring the curriculum system, 90.00% (72/80) of the students believed that the establishment of characteristic teaching courses could help to stimulate the enthusiasm for exploring TCM sciences, and 88.75% (71/80) of the students recognized the unique integration of textbooks, believing that it could help to understand the Lingnan school of Orthopedics. In terms of professional qualities, 90.00% (72/80) of the students agreed that the learning model of "systematic education+learning from teachers" could significantly help with the integration of knowledge, and 88.75% (71/80) of the students suggested that this model could stimulate the interest in specialized knowledge fields and motivate students to learn independently. In terms of apprenticeships with teachers, 85.00% (68/80) of the students reported that they could receive answers from teachers when asking questions, and 93.75% (75/80) of the students believed that early apprenticeship with a teacher was necessary. Some students still had a lack of understanding of learning TCM Qigong methods and believed that continuous practice took up too much personal time, failing to cultivate a good thinking of "the combination of medical sciences and martial arts", and they also believed that there were still limited opportunities for practice. The results show that the teaching model of "systematic education+learning from teachers" helps to improve the degree of satisfaction among students and cultivate clinical skills and professional qualities.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To explore the application effect of high-fidelity intelligent simulator combined with scenario simulation for emergency response training in the Department of Radiology, and to improve the emergency preparedness of medical, nursing, and technical staff in managing contrast agent adverse reactions.Methods:From January to July 2024, 132 medical, nursing, and technical staff from the Department of Radiology of a tertiary hospital in Chengdu City, China were selected as the training subjects. The high-fidelity intelligent simulator combined with scenario simulation teaching mode was used to conduct emergency response training for the participants. The differences in theoretical knowledge and post competence regarding contrast agent adverse reactions among the staff were compared before and after the training. A self-made questionnaire was used to investigate their needs and satisfaction of the emergency response training. SPSS 26.0 was used for data analysis. The differences in theoretical knowledge and post competence scores before and after training were compared using the paired samples t test. Results:After the training, the average score of theoretical knowledge examination increased from (84.32±10.19) points to (90.34±7.87) points, and the difference was statistically significant ( P<0.001). After the training, the scores of knowledge reserve, operational skills, situational decision-making ability, professional literacy, comprehensive literacy, and overall post competency were all significantly higher than those before the training ( P<0.05). The satisfaction score of emergency response training was (4.17±0.25) points. Conclusions:High-fidelity intelligent simulator combined with scenario simulation training improved the emergency preparedness and teamwork of radiology staff in clinical emergencies. The training received high recognition and satisfaction from the participants, which is of great significance for clinical emergency response and patient safety.

Working memory is an executive memory process that includes encoding, maintenance, and retrieval. These processes can be modulated by transcranial alternating current stimulation (tACS) with sinusoidal waves. However, little is known about the impact of the rate of current change on working memory. In this study, we aimed to investigate the effects of two types of tACS with different rates of current change on working memory performance and brain activity. We applied a randomized, single-blind design and divided 81 young participants who received triangular wave tACS, sinusoidal wave tACS, or sham stimulation into three groups. Participants performed n-back tasks, and electroencephalograms were recorded before, during, and after active or sham stimulation. Compared to the baseline, working memory performance (accuracy and response time) improved after stimulation under all stimulation conditions. According to drift-diffusion model analysis, triangular wave tACS significantly increased the efficiency of non-target information processing. In addition, compared with sham conditions, triangular wave tACS reduced alpha power oscillations in the occipital lobe throughout the encoding period, while sinusoidal wave tACS increased theta power in the central frontal region only during the later encoding period. The brain network connectivity results showed that triangular wave tACS improved the clustering coefficient, local efficiency, and node degree intensity in the early encoding stage, and these parameters were positively correlated with the non-target drift rate and decision starting point. Our findings on how tACS modulates working memory indicate that triangular wave tACS significantly enhances brain network connectivity during the early encoding stage, demonstrating an improvement in the efficiency of working memory processing. In contrast, sinusoidal wave tACS increased the theta power during the later encoding stage, suggesting its potential critical role in late-stage information processing. These findings provide valuable insights into the potential mechanisms by which tACS modulates working memory.
Humans ; Memory, Short-Term/physiology* ; Male ; Female ; Young Adult ; Transcranial Direct Current Stimulation/methods* ; Brain/physiology* ; Adult ; Electroencephalography ; Single-Blind Method

Objective:To investigate the effective ingredients and molecular mechanisms of Qizao oral liquid in the treatment of lead poisoning through network pharmacology and molecular docking technology.Methods:December 2023, the effective ingredients and their corresponding targets of Qizao oral liquid were searched from the TCM Systems Pharmacology database. Swiss Target Prediction was used to predict corresponding potential target genes of compounds. Targets associated with lead poisoning were obtained from GeneCards and OMIM databases. Cytoscape 3.10.1 software was employed to construct a components and corresponding target network as well as a components and corresponding target network, followed by visualization and cluster analysis. GO and KEGG enrichment analyses were conducted using the Metascape database, resulting in the generation of a signaling pathway-target network diagram. Molecular docking analysis between the principal compounds and target proteins was performed using Autodock 4.2.6 and Pymol 2.2.0 software to validate their underlying molecular mechanisms.Results:A total of 114 active chemical components, 361 potential targets, 2501 lead poisoning targets, and 191 intersection targets of "Qizao oral liquid and lead poisoning" were screened. Further analysis revealed that there were 2091 entries for GO biological processes and 202 KEGG signaling pathways. Enrichment analysis showed that the key targets were mainly enriched in cancer, lipid and atherosclerosis, PI3K-Akt signaling pathways. Molecular docking showed that there were 14 combinations with binding energy<-5 kcal/mol, among which PIK3R1-β-sitosterol binding energy was -9.71 kcal/mol.Conclusion:The primary active components found in Qizao oral liquid, such as β-sitosterol, nuciferine, stephanine, and stigmasterol, have the potential to modulate key targets including PIK3R1, AKT1, TP53, and NFKB1. These components are capable of influencing the PI3K-Akt signaling pathway as well as lipid and atherosclerosis pathways in order to mitigate the adverse effects of lead exposure.

Objective:To summarize the clinical characteristics of 5 children with developmental epileptic encephalopathy type 17 (DEE17) caused by GNAO1 gene variants confirmed by whole-exome sequencing and analyze the features of their genetic variants. Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with GNAO1-related DEE17 in the Department of Neurology, Children′s Hospital of Soochow University from January 2019 to October 2024. Their clinical features, genetic testing results, neuroimaging findings, electroencephalogram (EEG) results, and treatment regimens were summarized. Follow-up was performed via telephone or outpatient visits. Results:Among the 5 diagnosed children (3 males, 2 females), the age of onset ranged from 2 days to 2 years, and the age at diagnosis ranged from 2 days to 6 years. Four children presented with seizures in the neonatal or infantile period, manifesting as hypotonia, developmental delay, and seizure types including generalized tonic-clonic, myoclonic, and epileptic spasms. One child had a later onset at 2 years, presenting with language delay, intellectual disability, and involuntary movements, followed by seizures at 6 years, including focal and generalized tonic-clonic seizures. Genetic testing revealed de novo heterozygous missense variants in GNAO1 in all 5 cases: c.119G>C (p.G40A), c.808A>C (p.N270H), c.808A>G (p.N270D), c.118G>C (p.G40R), and c.17G>T (p.S6I). Among these variants, c.119G>C and c.17G>T were previously unreported pathogenic variants. Neuroimaging showed nonspecific changes in 3 children (widened frontal-temporal subarachnoid space, delayed myelination) and abnormal white matter signals in 2 cases. Long-term video-EEG revealed abnormal discharges and background slowing in all cases: multifocal discharges in 4 cases and focal epileptiform discharges (left mid-temporal) in 1 case. Clinical seizures were captured in 3 cases: 1 with a burst-suppression pattern and 2 with hypsarrhythmia. All patients received 3 or more antiseizure medications. Four cases (cases 1-4) responded well to topiramate combination therapy, with 2 cases (cases 1, 2) achieving complete seizure freedom and 2 cases (cases 3, 4) experiencing more than a 50% reduction in seizures. One child (case 3) achieved seizure control with an adjunctive ketogenic diet. The late-onset case (case 5) required a combination of levetiracetam, oxcarbazepine, and valproate for seizure management. Conclusions:GNAO1 variants can lead to DEE17 with diverse seizure types, often requiring multiple antiseizure medications, among which topiramate is effective. Early-onset cases typically present with seizures and developmental delay, while late-onset cases may exhibit language delay, intellectual disability, movement disorders, and refractory epilepsy. Genetic testing should be performed early for timely diagnosis.

Objective:To investigate the effect of tumor necrosis factor α (TNF-α) on the permeability of blood labyrinth barrier in C57BL/6J male mice and its possible mechanism.Methods:As for the design of animal experiment, twenty male C57BL/6J mice aged 6-8 weeks were randomly divided into control group and cisplatin group with 10 mice in each group by software method. The control group was intraperitoneally injected with normal saline every day, and the cisplatin group was intraperitoneally injected with 4 mg/kg cisplatin for 4 consecutive days. After administration, auditory brainstem response (ABR) was used to detect hearing changes in mice. HE staining was used to observe the morphological changes of mouse cochlea vasculature. The expression of TNF-α was detected by immunohistochemistry and ELISA. The permeability of the blood labyrinth barrier was observed by Evans blue staining. With respect to the design of cell experiment, primarily cultured cochlea pericytes (PC) and endothelial cells (EC) were divided into EC group, EC+TNF-α group, EC+PC group, EC+PC+TNF-α group, EC+PC+TNF-α+SB-3CT (MMP-9/MMP-2 secretion inhibitor) group, PC group, PC+TNF-α group, PC+TNF-α+LY294002 (PI3K/AKT pathway inhibitor) group, PC+LY294002 group. The protein expressions of ZO-1, VE-cadherin, MMP-9, MMP-2, PI3K, p-PI3K, AKT, and p-AKT were detected by Western blot. TEER and FITC-dextran penetration experiment were used to detect EC resistance and monolayer EC permeability, respectively. The data were statistically analyzed using GraphPad Prism 8 software.Results:In animal experiment, compared with control group, the ABR response threshold of mice in cisplatin group was increased ( P<0.01). The vaccine ular structure of the cochlea was disordered red, wrinkled and vacuole increased. The extravasation of vascular red fluorescent dye increased ( P<0.05), and also, levels of serum TNF-α and cochlear veins increased ( P<0.01). In cell experiment, by treatment of EC with different concentrations of cisplatin, 20 μmol cisplatin led to the highest expression of TNF-α ( P<0.01). The expression of TNF-α was the highest after 3 h intervention in EC ( P<0.05). Compared with those in EC+PC group, the resistance value of EC was decreased, the permeability of monolayers EC was increased, the expression of ZO 1 and VE cadherin proteins was decreased, and however, the resistance value was increased and the permeability of EC was decreased after the intervention of SB-3CT in EC+PC+TNF-α group. The expressions of ZO-1 and VE-cadherin proteins were increased ( P<0.05). The expression of MMP-9 increased after TNF-α intervention ( P<0.05), the expression of MMP-2 had no significant change, and the expression of p-PI3K/PI3K and p-AKT/AKT were increased ( P<0.05). The expression of MMP-9 decreased in PC+TNF-α+LY294002 group ( P<0.05). Conclusion:The hearing loss of C57BL/6J male mice induced by cisplatin may be related to the increased release of TNF-α from the blood labyrinth barrier EC in the cochlear stria vascularis, and the activation of PI3K/AKT signaling pathway by TNF-α in PC, which increases the secretion of MMP-9 from PC, ultimately leads to the increased permeability of the blood labyrinth barrier.