Objective: To explore the effect of a computer assisted audiovisual combined intervention model on the core symptoms of children with autism spectrum disorder (ASD), in order to provide references for enriching intervention and treatment methods for ASD children. Methods: From December 2023 to March 2024, 36 ASD children aged 4-8 years were recruited from Tianjin Disabled Persons Rehabilitation Center and Xinxinyu Children s Rehabilitation Center, and were divided into a training group (22 cases) and a control group (14 cases). The training group completed a 12 week audiovisual training course (visual sessions:twice a week, for 50-60 minutes each session; auditory sessions:three times a week, for 15 minutes each time), while the control group received only conventional treatment interventions. Before and after the intervention, the core symptoms of ASD children were assessed using the Short Sensory Profile (SSP), Social Responsiveness Scale (SRS), and Repetitive Behavior Questionnaire-2 ( RBQ- 2). Eye tracking experiments were used to test preferences for social attention. Results: Before the intervention, there were no statistically significant differences in the total scores and factor scores of the SSP and RBQ-2 scales between the two groups ( t =-1.63, 0.38, both P >0.05). The SRS total score, social communication, and restricted interests and repetitive behavior factor scores of the training group (90.68±25.83, 33.36±11.80, 15.64±7.00) were significantly higher than those of the control group (72.29±19.84, 24.93±7.85, 10.21±5.67) ( t =2.27, 2.36, 2.43, all P <0.05). Children in the training group with higher social communication factor scores before the intervention scored lower than the control group at the post intervention test (simple slope=-14.17, t =-2.48, P = 0.02), while there was no statistically significant difference in post intervention scores between children with lower social communication factor scores before the intervention and the control group (simple slope=2.31, t =0.57, P >0.05). Eye tracking experiments showed that the total fixation time on geometric images decreased significantly more in the training group [ -4.56 (-11.42, 1.21)] compared to the control group [6.55 (-0.32, 16.53)] after the intervention ( Z=2.48, P <0.05). Conclusions The computer assisted audiovisual intervention model can effectively improve the core symptoms of ASD children with poorer social communication levels. The promotion of the intervention model needs to consider individual differences in ASD.

In recent years， repetitive transcranial magnetic stimulation （rTMS） has garnered significant attention as a therapeutic approach for sleep disorders in the elderly. However， the prevailing rTMS protocols are predominantly developed based on normative neurophysiological data derived from young adults and fail to incorporate individualized parameters tailored to the brain characteristics of the elderly. To address this gap， the consensus development group synthesized the latest evidence from 2010 to 2025 and established a standardized rTMS protocol specifically for elderly patients with sleep disorders. Adhering to the Appraisal of Guidelines for Research and Evaluation II （AGREE II） framework， systematically screened randomized controlled trials （RCTs） and systematic reviews regarding rTMS in the treatment of sleep disorders across various conditions. Meanwhile， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system was employed to rigorously grade the quality of evidence and the strength of recommendations. This consensus guideline delineates precise rTMS protocols for the management of sleep disorders in the elderly， highlights the adjustment of stimulation intensity according to scalp-cortex distance recommends either MRI‑guided neuronavigation or the Beam F3/F4 heuristic approach for accurate target localization， thereby providing precise rTMS intervention protocol for sleep disorders in the elderly， aiming to enhance clinical efficacy while ensuring treatment safety. ［Funded by National Key Research and Development Program （number， 2023YFC3603200）； General Program of Shenzhen Science and Technology Innovation Commission （number， JCYJ20240813112859008， JCYJ20240813112900002）； Youth Program of Shenzhen Kangning Hospital （number， KN2023A004）； www.guidelines-registry.cn number， PREPARE-2026CN530］

OBJECTIVE To explore the mechanism of Yiqi yangyin huazhuo tongluo formula in ameliorating diabetic kidney disease （DKD） based on the gut microbiota-lipopolysaccharide （LPS）/Caspase-11/gasdermin D （GSDMD） pathway.METHODS A DKD mouse model was established by high-fat and high-sugar diet combined with intraperitoneal injection of low-dose streptozotocin. The successfully modeled mice were randomly divided into model group， metformin group （positive control， 200 mg/kg） and Yiqi yangyin huazhuo tongluo formula group （32.4 g/kg， calculated as crude drug dosage）， with 10 mice in each group； another 10 mice were set as the control group. Mice were intragastrically administered with corresponding drug solutions or normal saline once a day for 8 consecutive weeks. After the last administration， serum glycolipid metabolism indicators and urinary renal function indicators of mice were determined； the pathological and morphological changes of renal and colonic tissues were observed； LPS contents in renal tissues， colonic contents and serum were detected. 16S rRNA high-throughput sequencing was performed for gut microbiota analysis of colonic contents. The protein expressions of Occludin and zonula occludens-1 （ZO-1） in colonic tissues as well as Caspase-11 and GSDMD in renal tissues were detected.RESULTS Compared with the control group， the model group exhibited significantly elevated levels of serum fasting blood glucose， triglyceride， total cholesterol， serum creatinine， blood urea nitrogen and microalbumin， LPS contents in each sample， as well as protein expressions of Caspase-11 and GSDMD in renal tissues （ P ＜0.05）. The protein expressions of ZO-1 and Occludin in colonic tissues， together with Chao1 and Ace indices of gut microbiota， were markedly decreased （ P ＜0.05）， and the ratio of Firmicutes to Bacteroidetes was abnormally increased. Obvious histopathological changes were observed in renal and colonic tissues； the percentage of PAS-positive area in kidney was markedly increased （ P ＜0.05）. Compared with the model group， the Yiqi yangyin huazhuo tongluo formula group showed remarkable reductions in glycolipid metabolism and renal function-related indicators（except total cholesterol）， LPS contents in various samples， and renal protein expressions of Caspase-11 and GSDMD （ P ＜0.05）. The protein expression level of ZO-1 in colonic tissues and the Ace index of gut microbiota were significantly increased （ P ＜0.05）， and the relative abundance of beneficial genera including Bifidobacterium ， Faecalibaculum and Akkermansia in the gut microbiota was elevated.CONCLUSIONS The mechanism by which Yiqi yangyin huazhuo tongluo formula ameliorates DKD may be related to reshaping gut microbiota， repairing intestinal mucosal barrier， reducing LPS translocation into blood， and further inhibiting Caspase-11/GSDMD-mediated pyroptosis in kidney.

OBJECTIVES: To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism. METHODS: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay. RESULTS: MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera. CONCLUSIONS YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Animals ; MicroRNAs/genetics* ; Podocytes/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Autophagy/drug effects* ; Rats, Wistar ; Protein Kinases/metabolism* ; Rats ; Forkhead Box Protein O1 ; Mice ; Mitochondria/drug effects* ; Ubiquitin-Protein Ligases/metabolism* ; Glucose ; Diabetic Nephropathies ; Male ; Membrane Proteins/metabolism* ; Intracellular Signaling Peptides and Proteins

Objective:To investigate the role of calcium-binding protein S100A9 in acute lung injury induced by hepatic ischemia-reperfusion (HIR) in mice, and to explore its relationship with nuclear factor erythroid 2-related factor 2 (Nrf2).Methods:A total of 12 specific pathogen-free (SPF) male wild-type (WT) and 12 S100A9 knockout (S100A9 KO) C57BL/6J mice aged 6~8 weeks and weighing 20-25 g were randomly divided into four groups using a random number table: WT+Sham group, S100A9 KO+Sham group, WT+HIR group, and S100A9 KO+HIR group ( n=6 per group). The HIR model was established by clamping the portal vein and hepatic artery of the left and median liver lobes for 60 minutes followed by reperfusion. At 6 hours post-reperfusion, mice were anesthetized again, and blood samples were collected from the inferior vena cava. Both lungs were harvested. The lung wet-to-dry (W/D) weight ratio was measured. Hematoxylin and eosin (HE) staining was used to assess histopathological changes and calculate lung injury scores. The levels of inflammatory markers—S100A9, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) —as well as oxidative stress indicators including myeloperoxidase (MPO), reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum and lung tissue were measured. Western blotting was used to assess the expression levels of nuclear and cytoplasmic Nrf2, and cytoplasmic HO-1. Results:Compared with the WT+Sham group, both the WT+HIR and S100A9 KO+HIR groups showed significantly increased lung injury scores, W/D ratio, TNF-α, IL-6, ROS, MPO, and MDA levels (all P<0.05). Compared with the WT+HIR group, the S100A9 KO+HIR group exhibited significantly reduced levels of these indicators (all P<0.05). Moreover, the S100A9 KO+HIR group showed elevated nuclear Nrf2 expression and decreased cytoplasmic Nrf2 expression, accompanied by increased expression of HO-1, Gclm, Gclc, and Nqo1 (all P<0.05). Conclusion:Upregulation of S100A9 is involved in the development of HIR-induced acute lung injury, possibly through inhibition of Nrf2 nuclear translocation.

Objective:To establish the diagnosis and treatment strategies of tirofiban induced extremely severe thrombocytopenia to provide reference for laboratory stuffs and clinicians in early accurate identification and appropriate intervention.Methods:This study is a single-center retrospective study. The clinical data of patients with acute coronary syndrome treated at Fuwai Central China Cardiovascular Hospital from June 1st, 2019, to December 31st, 2024, were collected. 12 cases of extremely severe thrombocytopenia following tirofiban treatment were selected based on inclusion and exclusion criteria. The cohort comprised 10 males and 2 females, with a mean age of (66.08±7.08) years old. Clinical parameters including tirofiban administration duration, platelet count fluctuations, concomitant medications, treatment strategies, and complications were collected. The clinical characteristics of the data were analyzed and diagnostic-therapeutic flowchart was summarized. Normality was assessed using the Shapiro-Wilk test, and intergroup comparisons were performed using the Paired t-test or Wilcoxon test, and a P<0.05 was considered statistically significant.Results:All 12 patients had generally normal baseline platelet counts [(166.50±35.27)×10 9/L], but developed severe thrombocytopenia [(4.00±2.98)×10 9/L] after tirofiban treatment(P<0.001). 10 patients had the lowest platelet count within 24 hours using tirofiban, and the lowest platelet count occurred at 37 hours and 42 hours in 2 patients. 11 patients discontinued antithrombotic therapy after thrombocytopenia, and 10 patients resumed antithrombotic therapy after their platelet counts recovered above 30×10 9/L. 3 patients received platelet transfusions, while 10 patients were treated with thrombopoietin agents in combination with high-dose glucocorticoid pulse therapy. The time from discontinuation of tirofiban to platelet recovery above 50×10 9/L was (2.75±1.06) days. Major complications included bleeding manifestations ( n=6) and allergic-like reactions ( n=3). Based on the above clinical diagnosis and treatment information, a diagnosis and treatment flow chart for extremely severe thrombocytopenia caused by tirofiban was developed. Conclusion:When using tirofiban in clinical practice, platelet count should be monitored as early as possible to promptly identify tirofiban-induced extremely severe thrombocytopenia. The antithrombotic regimen and platelet-increasing treatment should be dynamically adjusted based on the patient′s condition.

Objective: This study aims to investigate the therapeutic effects and underlying mechanisms of Xuanfei Baidu Decoction (XFBD) in a mouse model of dampness-heat toxin pneumonia. By exploring how XFBD exerts its effects, we seek to deepen our understanding of its role in treating pulmonary diseases and to address the current knowledge gap regarding its mechanisms of action, thereby supporting its clinical application. Methods: Ultra-high-performance liquid chromatography and high-resolution mass spectrometry (HRMS) were employed to analyze the chemical constituents of XFBD. The protective effects of XFBD were evaluated using a dampness-heat toxin-induced mouse model, established through dampness-heat exposure and HCoV-229E infection. XFBD was administered orally, followed by assessments including lung index measurement, micro-CT imaging, viral load quantification, cytokine analysis, and histological evaluation via hematoxylin-eosin staining. Proteomics and single-cell transcriptomic analyses were conducted to explore the potential mechanisms underlying XFBD’s pharmacological effects. A cellular model of HCoV-229E infection was developed to investigate changes in the cAMP/PKA signaling pathway. Molecular docking and surface plasmon resonance (SPR) experiments confirmed the strong binding affinity between key XFBD components and PKA. Finally, PKA activators and inhibitors were applied in vitro to validate these mechanistic findings. Results: In vivo studies demonstrated that XFBD significantly reduced the lung index, improved the structural integrity of lung and tongue tissues, and decreased levels of proinflammatory mediators, including IL-6, IL-8, and TNF-α. Proteomic and single-cell transcriptomic analyses showed that the differentially expressed proteins after XFBD treatment were primarily associated with inflammatory responses and immune regulation. The cAMP/PKA signaling pathway was identified as a key mechanism underlying these therapeutic effects. Notably, Western blot, ELISA, molecular docking, and SPR analyses confirmed that XFBD elevated cAMP levels and p-PKA expression, thereby activating the cAMP/PKA signaling pathway in vitro. Conclusion: This study demonstrated that XFBD significantly alleviates symptoms in mice with dampness-heat toxin pneumonia. Its therapeutic effects are mediated, at least in part, through activation of the cAMP/PKA signaling pathway. These findings provide compelling evidence that XFBD is an effective herbal remedy against HCoV-229E infection.

Intracranial atherosclerotic stenosis (ICAS) is a common cause of ischemic stroke. The evaluation of its structure and function is of great significance for formulating clinical intervention strategies. The indications for endovascular treatment of ICAS lesions in the past were mainly based on the degree of luminal stenosis showed by cerebral angiography, which had certain limitations. The translesional pressure ratio (PR), as an important indicator for functional assessment after arterial stenosis, has gradually received attention in the evaluation of ICAS lesions in recent years. This article reviews the evaluation methods and clinical significance of PR in ICAS lesions.

Objective:To investigate the predictive value of elevated calprotectin S100A9 (S100A9) concentration during living-donor liver transplantation (LDLT) for early acute lung injury (ALI) in children with biliary atresia.Method:A retrospective analysis was conducted on 280 pediatric patients with biliary atresia who underwent LDLT using hyperreduced left lateral segment grafts at Tianjin First Central Hospital between January 2019 and January 2021. Based on intraoperative serum S100A9 levels at 30 minutes after graft reperfusion, patients were divided into the high S100A9 group (≥9.05 μg/L, 141 cases) and the low S100A9 group (<9.05 μg/L, 139 cases). General clinical characteristics were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to examine the correlation between S100A9 levels and early postoperative ALI. The predictive value of risk factors was assessed using receiver operating characteristic (ROC) curve analysis with calculation of the area under the curve (AUC) .Result:A total of 280 eligible children were included in the study, with 141 in the high S100A9 group and 139 in the low S100A9 group. The incidence of ALI was significantly higher in the high S100A9 group (31.2%) compared to the low S100A9 group (10.8%). Multivariate regression analysis identified elevated preoperative creatinine levels ( OR=1.191, 95% CI: 1.069~1.321, P=0.002), increased intraoperative S100A9 concentrations ( OR=1.426, 95% CI: 1.272~1.599, P=0.021), and higher intraoperative blood transfusion volume ( OR=0.985, 95% CI: 0.973~0.997, P=0.017) as independent risk factors for postoperative ALI in pediatric LDLT. The predictive value of intraoperative S100A9 levels for ALI was significant, with an AUC of 0.816 (95% CI: 0.758~0.874), a sensitivity of 80.5%, a specificity of 73.7%, and an optimal cutoff value of 9.49 μg/L. Furthermore, preoperative albumin and creatinine levels were found to be correlated with increased intraoperative S100A9 levels. Conclusion:Elevated intraoperative S100A9 levels, increased preoperative creatinine levels, and higher intraoperative blood transfusion volumes are independent risk factors for early ALI following pediatric LDLT. S100A9 levels have strong predictive value for ALI occurrence, highlighting the need for perioperative monitoring and intervention strategies to improve postoperative outcomes.