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.

Crigler-Najjar syndrome(CNS)is an autosomal recessive genetic disorder caused by mutations in the UGT1A1 gene.This author retrospectively analyzes the clinical data of one patient presenting with postnatal hyperbilirubinemia,who was genetically diagnosed with CNS.Her clinical course,genetic characteristics,diagnostic and therapeutic approaches are discussed to enhance clinicians'understanding of this condition.The patient exhibited recurrent jaundice due to elevated unconjugated bilirubin(UCB)levels since birth.During this period,the gallstones were identified and surgically removed,yet her bilirubin levels did not improve.In March 2024,the patient presented to our hospital and underwent genetic testing via a third-party facility.The results revealed two risk variants in the UGT1A1 gene.After one week of oral phenobarbital administration,her UCB levels decreased by approximately 47%,confirming a diagnosis of CNS type Ⅱ.The patient is currently under active follow-up with regular monitoring of bilirubin levels.For the infants and children presenting with persistent,fluctuating,non-hemolytic,and non-hepatitic hyperbilirubinemia since birth,early genetic testing should be prioritized to establish the definitive diagnosis.

Objective To investigate the potential mechanism of Jianpi Qinghua Granules in treating gastroesophageal reflux disease(GERD)with spleen deficiency and damp heat syndrome.Methods Six of 50 SPF male SD rats were randomly selected as the sham-operation group,the other 44 rats were treated with modified esophagoduodenostomy+abnormal hunger and satiety+internal and external damp heat intervention to establish GERD model of spleen deficiency and damp heat syndrome.The modeled rats were randomly divided into model group,omeprazole group,sodium cromoglicate group and Jianpi Qinghua Granules low-,medium-and high-dosage group,with 6 rats in each group.Each group was intervened with corresponding measures.Pathological changes in esophageal tissue were observed,ELISA was used to detect serum and esophageal mucosal tissue contents of interleukin(IL)-1β,tumor necrosis factor-α(TNF-α),IL-6 and IL-10.Western blot was used to detect protein expressions of nuclear factor-κB(NF-κB)p65,mast cell tryptase(MCT),proteinase-activated receptor 2(PAR2),Toll-like receptor 4(TLR4),TNF receptor-associated factor 6(TRAF6)and transforming growth factor β-activated kinase 1(TAK1)in esophageal mucosal tissue,RT-qPCR was used to detect mRNA expressions of MCT,PAR2,TLR4 and TRAF6 in esophageal mucosal tissue.Results Compared with the sham-operation group,the esophageal mucosal epithelium in the model group was thickened,basal cells proliferated,cell gaps widened,tissue edema and inflammatory cells infiltration were observed;the contents of IL-1β,TNF-α and IL-6 in serum and esophageal mucosa significantly increased,while the content of IL-10 significantly decreased(P<0.01);the expressions of NF-κB p65,MCT,PAR2,TLR4,TRAF6,TAK1 protein and MCT,PAR2,TLR4,TRAF6 mRNA in esophageal mucosa significantly increased(P<0.01).Compared with the model group,the injury of esophageal mucosa in each treatment group was alleviated in varying degrees;the contents of IL-1β,TNF-α and IL-6 in serum and esophageal mucosa increased,while the content of IL-10 decreased,the expressions of NF-κB p65,MCT,PAR2,TLR4,TRAF6 and TAK1 protein in esophageal mucosa decreased,the mRNA expressions of MCT,PAR2,TLR4 and TRAF6 decreased,and the differences were statistically significant in Jianpi Qinghua Granules high-dosage group(P<0.01).Conclusion Jianpi Qinghua Granules can reduce the esophageal mucosal injury and inflammatory reaction in GERD rats with spleen deficiency and damp heat syndrome,and its mechanism may be related to the inhibition of TLR4/NF-κB pathway activation induced by LPS.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

Objective:This study employs a combination of single-cell sequencing and Mendelian randomization to explore the genetic associations and molecular mechanisms of Eomes in RCC.Methods:In this study,single-cell transcriptomic data from RCC tissues and adjacent normal tissues were extracted from the GEO database.The data were analyzed using R language and various packages such as Seurat,limma,and CellChat for cell cluster annotation,intercellular communication analysis,and differential expression analysis.Additionally,eQTL data related to differentially expressed genes were retrieved from the GWAS database as exposure variables,with RCC used as the outcome variable in Mendelian randomization analysis to identify the role of Eomes in RCC.Finally,GO functional enrichment and KEGG pathway analyses were conducted to explore the potential molecular mechanisms of Eomes.Results:Single-cell RNA sequencing revealed that B cells play a significant role in the heterogeneity of RCC.Mendelian randomization analysis indicated that Eomes is an important risk factor for RCC(P＜0.05).Furthermore,seven highly correlated specific SNPs were identified,including rs 17021298,rs2247056,rs2617170,rs3806624,rs55908509,rs6590334,and rs9420589.GO and KEGG enrichment analyses suggest that Eomes may be involved in early cell fate determination in renal cell carcinoma and participate in the regulation of Th1 and Th2 cell differentiation,HPV infection,and the Notch signaling pathway.Conclusions:This study is the first to combine single-cell sequencing and Mendelian randomization analysis in RCC,confirming a strong positive causal relationship between Eomes and RCC(OR＞1).Our findings offer new insights into the pathogenesis of RCC,suggesting that Eomes could serve as a novel target for early diagnosis and personalized treatment of RCC.

Objective:This study employs a combination of single-cell sequencing and Mendelian randomization to explore the genetic associations and molecular mechanisms of Eomes in RCC.Methods:In this study,single-cell transcriptomic data from RCC tissues and adjacent normal tissues were extracted from the GEO database.The data were analyzed using R language and various packages such as Seurat,limma,and CellChat for cell cluster annotation,intercellular communication analysis,and differential expression analysis.Additionally,eQTL data related to differentially expressed genes were retrieved from the GWAS database as exposure variables,with RCC used as the outcome variable in Mendelian randomization analysis to identify the role of Eomes in RCC.Finally,GO functional enrichment and KEGG pathway analyses were conducted to explore the potential molecular mechanisms of Eomes.Results:Single-cell RNA sequencing revealed that B cells play a significant role in the heterogeneity of RCC.Mendelian randomization analysis indicated that Eomes is an important risk factor for RCC(P＜0.05).Furthermore,seven highly correlated specific SNPs were identified,including rs 17021298,rs2247056,rs2617170,rs3806624,rs55908509,rs6590334,and rs9420589.GO and KEGG enrichment analyses suggest that Eomes may be involved in early cell fate determination in renal cell carcinoma and participate in the regulation of Th1 and Th2 cell differentiation,HPV infection,and the Notch signaling pathway.Conclusions:This study is the first to combine single-cell sequencing and Mendelian randomization analysis in RCC,confirming a strong positive causal relationship between Eomes and RCC(OR＞1).Our findings offer new insights into the pathogenesis of RCC,suggesting that Eomes could serve as a novel target for early diagnosis and personalized treatment of RCC.

Objective To investigate the potential mechanism of Jianpi Qinghua Granules in treating gastroesophageal reflux disease(GERD)with spleen deficiency and damp heat syndrome.Methods Six of 50 SPF male SD rats were randomly selected as the sham-operation group,the other 44 rats were treated with modified esophagoduodenostomy+abnormal hunger and satiety+internal and external damp heat intervention to establish GERD model of spleen deficiency and damp heat syndrome.The modeled rats were randomly divided into model group,omeprazole group,sodium cromoglicate group and Jianpi Qinghua Granules low-,medium-and high-dosage group,with 6 rats in each group.Each group was intervened with corresponding measures.Pathological changes in esophageal tissue were observed,ELISA was used to detect serum and esophageal mucosal tissue contents of interleukin(IL)-1β,tumor necrosis factor-α(TNF-α),IL-6 and IL-10.Western blot was used to detect protein expressions of nuclear factor-κB(NF-κB)p65,mast cell tryptase(MCT),proteinase-activated receptor 2(PAR2),Toll-like receptor 4(TLR4),TNF receptor-associated factor 6(TRAF6)and transforming growth factor β-activated kinase 1(TAK1)in esophageal mucosal tissue,RT-qPCR was used to detect mRNA expressions of MCT,PAR2,TLR4 and TRAF6 in esophageal mucosal tissue.Results Compared with the sham-operation group,the esophageal mucosal epithelium in the model group was thickened,basal cells proliferated,cell gaps widened,tissue edema and inflammatory cells infiltration were observed;the contents of IL-1β,TNF-α and IL-6 in serum and esophageal mucosa significantly increased,while the content of IL-10 significantly decreased(P<0.01);the expressions of NF-κB p65,MCT,PAR2,TLR4,TRAF6,TAK1 protein and MCT,PAR2,TLR4,TRAF6 mRNA in esophageal mucosa significantly increased(P<0.01).Compared with the model group,the injury of esophageal mucosa in each treatment group was alleviated in varying degrees;the contents of IL-1β,TNF-α and IL-6 in serum and esophageal mucosa increased,while the content of IL-10 decreased,the expressions of NF-κB p65,MCT,PAR2,TLR4,TRAF6 and TAK1 protein in esophageal mucosa decreased,the mRNA expressions of MCT,PAR2,TLR4 and TRAF6 decreased,and the differences were statistically significant in Jianpi Qinghua Granules high-dosage group(P<0.01).Conclusion Jianpi Qinghua Granules can reduce the esophageal mucosal injury and inflammatory reaction in GERD rats with spleen deficiency and damp heat syndrome,and its mechanism may be related to the inhibition of TLR4/NF-κB pathway activation induced by LPS.