Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance， while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine （TCM） has a long history in the prevention and management of this condition， demonstrating eight distinct advantages， including systematic theoretical foundation， diversified therapeutic approaches， definite therapeutic efficacy， high safety profile， good patient compliance， comprehensive intervention strategies， emphasis on prevention， and stepwise treatment protocols. Additionally， TCM is characterized by six distinctive features： the use of natural medicinal substances， non-invasive external therapies， integration of medicinal dietetics， simple exercise regimens， precise syndrome differentiation， and diverse dosage forms. By combining internal and external treatments， TCM facilitates individualized regimen adjustment and holistic regulation， demonstrating remarkable effects in improving obesity-related metabolic indicators， regulating constitutional imbalance， and promoting healthy behaviors. However， challenges remain， such as inconsistent operational standards， insufficient high-quality clinical evidence， and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment， conducting multicenter randomized controlled trials， and fostering interdisciplinary integration， so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.

BACKGROUND:Bone tissue loss caused by tumors and trauma can have an adverse effect on postoperative rehabilitation.Therefore,scaffold materials are usually implanted during treatment.However,the existing implant materials are relatively simple and lack antibacterial properties.Early implantation may lead to iatrogenic autoinfection and have an adverse effect on osteogenesis.OBJECTIVE:To construct a KR-12-a5 polypeptide-nanohydroxyapatite-small intestinal submucosa composite scaffold and evaluate its feasibility as a material for promoting bone defect repair.METHODS:The small intestinal submucosa scaffold and the small intestinal submucosa scaffold containing 25,50,and 100 mg/mL nanohydroxyapatite(referred to as nHA-SIS scaffold)were prepared by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide cross-linking method.The appropriate scaffold was screened for subsequent experiments by mechanical property testing.The antibacterial properties of KR-12-a5 polypeptide solution against Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum were detected.The nHA-SIS scaffolds were immersed in 250,500,and 1 000 μg/mL KR-12-a5 peptide solutions for 24 hours,and then freeze-dried to obtain peptide-loaded nanohydroxyapatite-porcine small intestinal submucosa composite scaffolds(denoted as P-nHA-SIS scaffolds).The sustained-release properties of the three groups of scaffolds were characterized.The nHA-SIS scaffolds and the three groups of P-nHA-SIS scaffolds were co-cultured with Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum for 24 hours or 48 hours.The scaffolds with strong antibacterial ability were screened by live and dead bacteria staining and scanning electron microscopy for subsequent experiments.The degradation properties and water absorption rates of the uncross-linked small intestinal submucosa scaffolds,cross-linked small intestinal submucosa scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were characterized.The extracts of cross-linked small intestinal submucosal scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were co-cultured with MC3T3-E1 cells.CCK-8 assay and live-dead cell staining were performed.The effects of the extracts of the three scaffolds on the migration of MC3T3-E1 cells were detected by Transwell chamber assay.RESULTS AND CONCLUSION:(1)The elastic modulus and compressive strength of 25,50,and 100 mg/mL nHA-SIS scaffolds were higher than those of small intestinal submucosal scaffolds(P＜0.05),among which the elastic modulus and compressive strength of 25 mg/mL nHA-SIS scaffolds were the highest,and this group of scaffolds were selected for subsequent experiments to load peptides.(2)KR-12-a5 peptide had strong antibacterial activity against common bacteria in bone defects(Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum).The three groups of P-nHA-SIS scaffolds all had sustained release properties.With the increase of peptide mass concentration,the antibacterial property of P-nHA-SIS scaffold was enhanced.Among them,the P-nHA-SIS scaffold loaded with 500 μg/mL peptide had achieved a satisfactory antibacterial effect,and this group of scaffolds would be selected in the future.(3)The degradation rate of the three groups of cross-linked scaffolds was lower than that of the uncross-linked scaffolds,and the water absorption rate was greater than that of the uncross-linked scaffolds.P-nHA-SIS scaffolds could promote the proliferation and migration of MC3T3-E1 cells without affecting the activity of MC3T3-E1 cells.(4)The results show that P-nHA-SIS scaffolds have strong antibacterial properties and the ability to promote the proliferation and migration of MC3T3-E1 cells,and are expected to be used in bone defect repair.

Objective To explore the effectiveness of the generative large language model MedGo in nursing decision-making for elderly patients with multimorbidity. Methods A quasi-randomized controlled trial study was conducted involving 6 junior nurses, 6 senior nurses and the MedGo model from January 1, 2025 to March 31, 2025 at the Emergency Internal Medicine Ward of Shanghai East Hospital Affiliated to Tongji University. Clinical data of 120 elderly patients with multimorbidity were analyzed to compare the performance of the three groups in four tasks (nursing diagnosis assessment, nursing intervention formulation, complication identification, and complication prevention) from three evaluation dimensions: decision-making time consumption, decision accuracy, and decision-making quality. Results In terms of decision-making time, the senior nurse group completed all four tasks faster than the junior nurse group (P＜0.01), and the MedGo group completed all four tasks faster than the junior nurse group (P＜0.001) and the senior nurse group (P＜0.001). In terms of decision-making accuracy, senior nurse group scored higher than junior nurse group in all four tasks (P＜0.001), while the MedGo group outperformed the senior nurse group only in complication identification (P＜0.001). In terms of decision-making quality, the MedGo group scored higher than junior nurse group (P＜0.001) and senior nurse group (P＜0.001) in all four tasks. Conclusions The MedGo model demonstrates advantages of high efficiency, accuracy, and quality in nursing decision-making for elderly patients with multimorbidity; senior nurses outperform junior nurses in decision-making, providing diverse references for clinical nursing decision-making.

BACKGROUND:Bone tissue loss caused by tumors and trauma can have an adverse effect on postoperative rehabilitation.Therefore,scaffold materials are usually implanted during treatment.However,the existing implant materials are relatively simple and lack antibacterial properties.Early implantation may lead to iatrogenic autoinfection and have an adverse effect on osteogenesis.OBJECTIVE:To construct a KR-12-a5 polypeptide-nanohydroxyapatite-small intestinal submucosa composite scaffold and evaluate its feasibility as a material for promoting bone defect repair.METHODS:The small intestinal submucosa scaffold and the small intestinal submucosa scaffold containing 25,50,and 100 mg/mL nanohydroxyapatite(referred to as nHA-SIS scaffold)were prepared by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide cross-linking method.The appropriate scaffold was screened for subsequent experiments by mechanical property testing.The antibacterial properties of KR-12-a5 polypeptide solution against Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum were detected.The nHA-SIS scaffolds were immersed in 250,500,and 1 000 μg/mL KR-12-a5 peptide solutions for 24 hours,and then freeze-dried to obtain peptide-loaded nanohydroxyapatite-porcine small intestinal submucosa composite scaffolds(denoted as P-nHA-SIS scaffolds).The sustained-release properties of the three groups of scaffolds were characterized.The nHA-SIS scaffolds and the three groups of P-nHA-SIS scaffolds were co-cultured with Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum for 24 hours or 48 hours.The scaffolds with strong antibacterial ability were screened by live and dead bacteria staining and scanning electron microscopy for subsequent experiments.The degradation properties and water absorption rates of the uncross-linked small intestinal submucosa scaffolds,cross-linked small intestinal submucosa scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were characterized.The extracts of cross-linked small intestinal submucosal scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were co-cultured with MC3T3-E1 cells.CCK-8 assay and live-dead cell staining were performed.The effects of the extracts of the three scaffolds on the migration of MC3T3-E1 cells were detected by Transwell chamber assay.RESULTS AND CONCLUSION:(1)The elastic modulus and compressive strength of 25,50,and 100 mg/mL nHA-SIS scaffolds were higher than those of small intestinal submucosal scaffolds(P＜0.05),among which the elastic modulus and compressive strength of 25 mg/mL nHA-SIS scaffolds were the highest,and this group of scaffolds were selected for subsequent experiments to load peptides.(2)KR-12-a5 peptide had strong antibacterial activity against common bacteria in bone defects(Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum).The three groups of P-nHA-SIS scaffolds all had sustained release properties.With the increase of peptide mass concentration,the antibacterial property of P-nHA-SIS scaffold was enhanced.Among them,the P-nHA-SIS scaffold loaded with 500 μg/mL peptide had achieved a satisfactory antibacterial effect,and this group of scaffolds would be selected in the future.(3)The degradation rate of the three groups of cross-linked scaffolds was lower than that of the uncross-linked scaffolds,and the water absorption rate was greater than that of the uncross-linked scaffolds.P-nHA-SIS scaffolds could promote the proliferation and migration of MC3T3-E1 cells without affecting the activity of MC3T3-E1 cells.(4)The results show that P-nHA-SIS scaffolds have strong antibacterial properties and the ability to promote the proliferation and migration of MC3T3-E1 cells,and are expected to be used in bone defect repair.

Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Tuberculosis （TB） is a major infectious disease that seriously endangers public health. In traditional Chinese medicine （TCM）， TB is considered to be caused by "exogenous latent tuberculosis pathogens"， and whether the disease occurs depends on the strength of healthy Qi. The disease course is characterized by five features： Hidden latency， pathological accumulation， triggering due to deficiency of healthy Qi， depletion of healthy Qi， and prolonged progression with difficulty in recovery. The latent stage is based on the fundamental pathogenesis of "specific latent pathogens concealed in the lung collaterals and waiting for the appropriate time to manifest"， which exhibits the temporal and spatial characteristics of latent pathogens. During this stage， Mycobacterium tuberculosis remains in a dormant state and maintains a dynamic balance with the host immune system. The triggering and progression stages are characterized by the core pathogenesis of "deficiency of healthy Qi initiating pathogenic factors and excessive pathogenic factors triggering disease". Immune dysfunction may lead to severe pathological damage to the structure of the lung collaterals. The key pathogenesis of the latent-retention stage is "persistent latent pathogens consuming healthy Qi"， which is also the core reason for the difficulty in treating initial TB onset， prolonged disease progression， and recurrent attacks. Based on the theory of latent pathogens， this study establishes a four-stage prevention and treatment system "with pathogenesis as the guiding principle and disease stages as the criteria". The corresponding therapeutic principles include tonifying Qi and nourishing Yin， clearing and transforming latent phlegm， regulating and tonifying the spleen and kidney， strengthening healthy Qi and replenishing the primordial Qi， nourishing Yin and reducing fire， suppressing and eliminating tuberculosis pathogens， tonifying deficiency， restoring primordial Qi， clearing residual pathogens， and eliminating pathogenic factors. Guided by the theory of latent pathogens， this article systematically elucidates the TCM connotation of M. tuberculosis invasion of the lung collaterals and the staged syndrome differentiation and treatment approach， providing theoretical foundations and practical guidance for the prevention and treatment of TB through integrated Chinese and Western medicine and offering new perspectives for the prevention and control of infectious diseases using TCM.

In recent years,more and more researches has focused on the correlation between cognitive activity and physiological variables.The change of pupil is regarded as an important target in the cognitive process,and has become a hot research field.This review focuses on the three key brain regions that regulate pupil change,and reflects the neurophysiological mechanism behind pupil change by elaborating the neural pathways related to pupil change and cognitive performance.Based on recent studies on pupil change in cognitive diseases,it aims to promote the application of pupil change in the field of cognitive science in the future.

ObjectiveTo identify key factors influencing cognitive function in the elderly, including traditional Chinese medicine (TCM) constitutional classification, and to rank their relative importance.MethodsWe used cross-sectional data from seven geographical regions across mainland China. The Changsha version of the Montreal Cognitive Assessment was used to assess cognitive function. A “least absolute shrinkage and selection operator” (LASSO) model, multivariate linear regression analysis, and random forest (RF) model were used. Subgroup analyses were performed to examine the correlation between key TCM constitution types and cognitive function in different population subgroups.ResultsA total of 24 803 individuals aged 60 and above were included in the study. We selected 18 influential factors using the LASSO model. Higher education, being married, and having insurance were positively correlated with cognitive function in the elderly (all P .05). In contrast, poor sleep, vision impairment, hearing impairment, basic activities of daily living disability, instrumental activities of daily living disability, depression, hypertension, coronary heart disease, diabetes, stroke, yang-deficiency constitution (YADC), yin-deficiency constitution (YIDC), qi deficiency constitution (QDC), and blood stasis constitution (BSC) were negatively correlated with cognitive function (all P .05). YIDC and BSC affected all dimensions of cognitive function (all P .05). YADC mainly affected attention, language, abstraction (verbal analogies), memory, and orientation to time and place dimensions (P .001). QDC mainly affected language and abstraction (verbal analogies) dimensions (P .05). The negative correlations between BSC, YADC, YIDC, and QDC scores and cognitive function revealed statistically significant differences across most subgroups. The RF model identified education, BSC, and poor sleep quality as the three most influential factors in our study.ConclusionBSC, YADC, YIDC, and QDC were associated with cognitive decline in the elderly. Our findings provide new perspectives and significant references for interventions for early-stage cognitive disorders.

OBJECTIVE: To carry out genetic testing and clinical phenotypic characterization on a four-generation Chinese pedigree affected with Stickler syndrome type I and explore its genotype-phenotype correlation. METHODS: A child presented at the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in February 2023 for micrognathia, glossoptosis and cleft palate and his family members were selected as the study subjects. Clinical data were collected from the affected members, and peripheral blood samples were obtained from 17 participants (including 4 patients and 13 asymptomatic individuals). Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genotype-phenotype correlation was analyzed by integrating the sequencing data with evidence from existing literature. This study has bee granted by the Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine and Guangzhou Women and Children's Medical Center (Ethics No.: 2022-406B00). RESULTS: The four-generation pedigree has comprised 19 members. In addition to the proband, 5 affected individuals had manifested with high myopia, congenital cataracts, and progressive vision loss. Two deceased members reportedly exhibited similar ocular manifestations. Among the four living patients, two had developed retinal detachment, while two others presented with chronic joint pain onset between 35 ~ 40 years of age. One patient required hip replacement surgery at age 42 secondary to femoral head necrosis. The proband, the youngest affected member, exhibited characteristic phenotypes including congenital micrognathia and cleft palate, consistent with Pierre-Robin syndrome. Genetic analysis revealed a heterozygous nonsense mutation in COL2A1 (NM_001844.5: c.2668C>T; p.Gln890Ter) segregating with the disease in all four symptomatic patients. This variant was absent in asymptomatic family members and unaffected controls. While the mutation is listed in ClinVar, no clinical case report has associated it with this phenotypic spectrum. It was not recorded in population databases (gnomAD v4.1.0, 1000 Genomes Project, or ExAC), supporting its potential pathogenicity. CONCLUSION This study has diagnosed a four-generation Chinese pedigree with Stickler syndrome type I attributed to the pathogenic COL2A1 variant c.2668C>T (p.Gln890Ter), which is a rare nonsense mutation associated with ocular predominance and variable skeletal involvement. Notably, this family exhibited marked clinical heterogeneity despite sharing the identical genotype, which highlighted the challenges in phenotype-genotype correlation. The autosomal dominant transmission pattern observed in this pedigree has provided critical insights into COL2A1-related collagenopathies and underscored the necessity of ultrasonographic monitoring for ocular anomalies during prenatal diagnosis. Above findings have advanced our understanding of the pleiotropic effects in type Ⅱ collagen disorders and laid the foundation for precision-based genetic counseling, enabling targeted cascade screening and implementation of tertiary prevention strategies against congenital disabilities for high-risk families.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Arthritis/genetics* ; Collagen Type II/genetics* ; Connective Tissue Diseases/genetics* ; Exome Sequencing ; Genetic Association Studies ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Mutation ; Pedigree ; Phenotype ; Retinal Detachment/genetics* ; East Asian People/genetics*