Objective: To investigate the associations between 24 hour activity and the quality of life (QoL) in children with autism spectrum disorder (ASD), and to explore their isotemporal substitution effects, providing a reference for developing intervention strategies of their QoL. Methods: From March to June 2025, 288 children with ASD from 7 special education schools in Jinan were selected by using a cluster random sampling method. The 24 hour activity was measured by using ActiGraph wGT3X-BT triaxial accelerometers, and their QoL was assessed by applying a parent proxy Pediatric Quality of Life Inventory. Multiple linear regression was employed to analyze the associations between 24 hour activity and QoL in children with ASD. Isotemporal substitution analysis was applied to analyze the dose response relationship of 24 hour activity time and the QoL scores in children with ASD. Results: Within the 24 hour activities of children with ASD, the daily time spent in sleep, sedentary behavior (SB), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were 610.49，605.80，195.49，28.22 minutes, respectively. Multiple linear regression analysis showed that, after controlling for confounding factors such as gender, age, and parental education level, the proportion of time spent in MVPA was positively associated with QoL scores ( β =1.75) in children with ASD, whereas the proportion of time spent in SB was negatively associated with QoL scores ( β =-1.00)(both P <0.01). In the dose response relationship, reallocating time from sleep, SB, and LPA to MVPA was associated with an improvement in QoL in children with ASD, with increased scores of 1.38, 1.55, 1.47, respectively; conversely, the reverse substitution was associated with a decline in QoL, and the scores decreased by 2.31, 2.99 and 2.68, respectively, with the latter demonstrating a more pronounced effect(all P <0.05). Conclusions Enhancing the QoL for children with ASD should be grounded in the overall balance of 24 hour activity. Time reallocation strategies should be implemented with an emphasis on relatively increasing MVPA and reducing SB.

Cardiotoxicity induced by antineoplastic agents is an important factor affecting the prognosis of cancer patients. This article systematically summarizes the clinical manifestations of cardiotoxicity caused by chemotherapeutic drugs, molecular targeted cancer therapies, and immunotherapeutic drugs, and identifies the core injury mechanisms, including cardiomyocyte apoptosis, oxidative stress, and mitochondrial dysfunction. In Traditional Chinese Medicine (TCM) theory, anticancer drug-induced cardiotoxicity falls under the category of “heat toxins” characterized by dual deficiency of qi and blood, upward flaming of heart heat, stagnation of the heart vessels, and meridian obstruction induced by phlegm-dampness. Therefore, by reviewing the preventive and therapeutic effects and the underlying mechanisms of tonic medicines, interior heat-clearing medicines, blood-circulating and stasis-resolving medicines, phlegm-transforming, cough-suppressing and panting-relieving medicines, and interior-warming medicines, this paper concludes that TCM prevention and treatment of this condition adheres to the formulation principle of “reinforcing healthy qi, removing toxins, and resolving blood stasis”. Its mechanisms of action—including antioxidation effects, regulation of autophagic balance, antagonism of inflammatory responses, and improvement of microcirculation—are highly consistent with modern medical treatment strategies (e.g., dexrazoxane for inhibiting iron-dependent oxidative stress, statins for anti-inflammatory effects). This study provides theoretical support and practical guidance for the collaborative and precise prevention and treatment of anticancer drug-induced cardiotoxicity through the integration of traditional Chinese and Western medicine.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

To analyze the clinical and genetic features of oculopharyngodistal myopathy (OPDM) patients and compare the phenotypic differences among various causative genes.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo explore the possible mechanism of Jianpi Huazhuo Tiaozhi Granule （健脾化浊调脂颗粒， JHTG） in treating atherosclerosis （AS） based on the regulation of perivascular adipose tissue （PVAT） browning via the phosphoinositide 3-kinase/protein kinase B （PI3K/AKT） signaling pathway. MethodsFifteen SPF male C57BL/6J mice served as control group， while 76 ApoE^-/- mice were first fed a high-fat diet for 16 weeks to establish AS model. After successful modeling， they were randomly divided into model group （n=16）， as well as the browning group， the low-， medium- and high-dose JHTG group， with 15 mice in each group. The browning group was intraperitoneally injected with β3-adrenergic receptor agonist CL 316243 at 1 mg/（kg·d） once daily. The low-， medium- and high-dose JHTG groups were treated with 4.3 g/（kg·d）， 8.6 g/（kg·d）， and 17.2 g/（kg·d） of JHTG by gavage， respectively， while the control group and the model group were given normal saline at 10 ml/（kg·d） by intragastric administration， once daily. All groups received continuous intervention for 4 weeks. The aorta was collected to assess the plaque ratio by gross oil red O staining. HE staining was used to measure the plaque area in cross-sections. Masson staining was employed to detect the proportion of collagen fibers in plaque. Transmission electron microscopy was used to observe the quantity and morphological changes of mitochondria and lipid droplets in adipocytes. The levels of serum triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected， as well as tumor necrosis factor α （TNF-α） and interleukin 6 （IL-6） levels in the PVAT and aorta. The protein levels of adiponectin and leptin in PVAT， and protein expression levels of phosphoinositide 3-kinase （PI3K）， phosphorylated phosphoinositide 3-kinase （p-PI3K）， protein kinase B （AKT）， phosphorylated protein kinase B （p-AKT）， uncoupling protein 1 （UCP1）， peroxisome proliferator-activated receptor γ coactivator 1α （PGC-1α）， and PR domain containing 16 （PRDM16） were measured. The mRNA expression levels of UCP1， PGC-1α and PRDM16 in PVAT were detected. ResultsCompared to the control group， the model group showed increased serum TG， TC， and LDL-C levels and decreased HDL-C level， elevated TNF-α and IL-6 levels in PVAT and aorta， decreased average fluorescence intensity of adiponectin， increased average fluorescence intensity of leptin， reduced p-PI3K/PI3K and p-AKT/AKT values as well as protein levels and mRNA expression levels of UCP1， PGC-1α and PRDM16 （P＜0.01）. The pathological results showed that no significant plaque formation was observed in the aortas of mice in the control group. In the model group， multiple plaques were observed in the aortas， with large numbers of foam cells， cholesterol crystals， and inflammatory cell aggregation in the plaques. Compared to the model group， the browning group and the high-dose JHTG group significantly improved the above indicators and aortic pathological changes （P＜0.05 or P＜0.01）. Three JHTG groups showed a dose-dependent effect in reducing LDL-C level and plaque ratio by gross oil red O staining， elevating the average fluorescence intensity of adiponectin， the p-AKT/AKT value， the protein level of PGC-1α， and the mRNA expression levels of UCP1 and PRDM16 （P＜0.05）. The high-dose JHTG group and the browning group showed similar efficacy in improving the pathology of the aorta. ConclusionJHTG may promote PVAT browning in AS model mice through the PI3K/AKT pathway， improve the endocrine function of PVAT， inhibit aortic inflammation， and thereby ameliorate the formation of AS plaques.

Neurodegenerative diseases such as Alzheimer's disease （AD）， Parkinson's disease （PD）， and Huntington's disease （HD） are increasingly becoming major challenges to global public health. The pathogenesis of these diseases is highly complex， with oxidative damage and ferroptosis emerging as potential core factors. Oxidative damage primarily results from the accumulation of reactive oxygen species （ROS） within cells， a process that impairs cellular function and viability. Ferroptosis， an iron-dependent form of programmed cell death， plays a crucial role in neuronal injury and apoptosis. Multiple studies indicate a significant interaction between oxidative damage and ferroptosis. This interplay not only accelerates the progression of neurodegenerative diseases but also offers new directions for potential therapeutic targets. This review systematically analyzes the mechanisms of oxidative damage and ferroptosis in various neurodegenerative diseases， evaluates current research frontiers， and explores feasible therapeutic strategies， aiming to provide new insights and perspectives for in-depth research in this field.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

BACKGROUND:Studies have confirmed that Pterocarya hupehensis skan total flavonoids(PHSTF)can improve the level of collagen-induced arthritis in rats,but there is still a lack of research on the regulation of Wnt/β-catenin signaling pathway in fibroblast-like synoviocytes and its effect on related cell functions.OBJECTIVE:To investigate the effect and mechanism of PHSTF on lipopolysaccharide-induced proliferation,migration and apoptosis of fibroblast-like synoviocytes based on the Wnt/β-catenin signaling pathwayMETHODS:Fibroblast-like synoviocytes were divided into control group,lipopolysaccharide group,lipopolysaccharide+low-,medium-,and high-dose PHSTF groups(10,20,and 40 μg/mL),lipopolysaccharide+Wnt pathway inhibitor DKK1 group,and lipopolysaccharide+Wnt pathway inhibitor DKK1+high-dose PHSTF group(40 μg/mL).The cell counting kit-8 method was used to detect the effect of PHSTF on the viability of fibroblast-like synoviocytes,and the final drug concentration and time were screened.Flow cytometry was used to detect the apoptosis of fibroblast-like synoviocytes.Cell scratch assay,EDU staining and cell cloning assay were used to detect the migration and proliferation of fibroblast-like synoviocytes.Western blot assay was used to detect the protein expression levels of Wnt3a,β-catenin,tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,Bax and Bcl-2 in fibroblast-like synoviocytes.RESULTS AND CONCLUSION:(1)Compared with the control group,the cell viability decreased significantly when the concentration of PHSTF was＞40 μg/mL(P＜0.01).Therefore,the drug concentration of≤40 μg/mL was selected for subsequent experiments.(2)Compared with the lipopolysaccharide group,the wound healing rate,cell clone formation rate and the number of EDU-positive cells in the low-,medium-and high-dose PHSTF groups were significantly reduced,while the apoptosis rate was significantly increased(P＜0.05-0.01).(3)Western blot results showed that compared with the lipopolysaccharide group,low-,medium-and high-dose PHSTF significantly inhibited cellular Wnt3a,β-catenin,cellular tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,and Bcl-2 protein expression,and promoted the expression of Bax protein(P＜0.01).(4)Compared with the DKK1 group,the combination of DKK1 and high-dose PHSTF significantly inhibited the protein expression of Wnt3a,β-catenin,matrix metalloproteinase 2,matrix metalloproteinase 9 and Bcl-2 protein expression and promoted the protein expression of Bax(P＜0.01).To conclude,PHSTF may inhibit the proliferation and migration of fibroblast-like synoviocytes and promote apoptosis by inhibiting the Wnt/β-catenin signaling pathway.