Abstract The prevalence of hyperuricemia (HUA) in children and adolescents is rising rapidly and presents a trend towards younger age groups, establishing it as the most prevalent metabolic abnormality and a major public health concern. To curb the damage of persistent HUA to children and adolescents development and health, the review systematically addresses the epidemiology, diagnosis, health impairments, and pathogenesis of pediatric HUA, summarizes risk factors and tiered interventions, and discusses future directions including diagnostic precision, the advancement of intervention windows, and the dual role of uric acid, with the goal of informing early prevention and control strategies for HUA in children and adolescents.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

OBJECTIVES: To investigate the risk factors of overall postoperative complications in elderly patients undergoing gastrointestinal surgeries. METHODS: This study was conducted among a total of 1388 elderly patients, who underwent elective gastrointestinal surgeries at 17 centers across China between April, 2020 and April, 2022. The primary outcome was the incidence of postoperative complications within 30 days, including procedure-related, neuropsychiatric, respiratory, cardiovascular, and gastrointestinal complications as well as acute kidney injury. Baseline characteristics, preoperative psychological and functional status, intraoperative anesthesia and surgical factors, intraoperative medication, use of nerve block, and postoperative analgesia methods were compared between the patients experiencing one or more postoperative complications and those without complications. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for postoperative complications. The relationship between postoperative acute pain and each type of complication were explored. RESULTS: The incidence of overall postoperative complications was 50.8% (705/1388) in these patients. Multivariate analysis showed that age (OR: 1.026; 95% CI: 1.006-1.046), prognostic nutritional index (OR: 0.998; 95% CI: 0.997-1.000), preoperative EuroQol-5 dimensions score (OR: 0.094; 95% CI: 0.018-0.500), blood loss (OR: 1.002; 95% CI: 1.001-1.003), and acute postoperative pain (OR: 1.308; 95% CI: 1.033-1.657) were significantly associated with the occurrence of postoperative complications. Specifically, patients experiencing severe postoperative pain had a significantly higher incidence of neuropsychiatric (27.2% vs 19.8%), procedure-related (17.3% vs 10.2%), and cardiovascular complications (3.6% vs 1.7%). CONCLUSIONS An advanced age, a low preoperative nutritional index, a poor quality of life score, a greater volume of intraoperative blood loss, and acute postoperative pain are independent risk factors for postoperative complications in elderly patients undergoing gastrointestinal surgeries. There is a significant association between acute postoperative pain and multi-system complications.
Humans ; Postoperative Complications/etiology* ; Aged ; Risk Factors ; Digestive System Surgical Procedures/adverse effects* ; Male ; Female ; China/epidemiology* ; Pain, Postoperative/epidemiology* ; Incidence ; Aged, 80 and over

Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome, with implications for microbial pathogenesis and host defense. Among these, transfer RNA-derived small RNAs (tsRNAs) have garnered attention for their roles in modulating microbial behavior. However, the bacterial factors mediating tsRNA interaction and functionality remain poorly understood. In this study, using RNA affinity pull-down assay in combination with mass spectrometry, we identified a putative membrane-bound protein, annotated as P-type ATPase transporter (PtaT) in Fusobacterium nucleatum (Fn), which binds Fn-targeting tsRNAs in a sequence-specific manner. Through targeted mutagenesis and phenotypic characterization, we showed that in both the Fn type strain and a clinical tumor isolate, deletion of ptaT led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition. Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between Fn wild type and PtaT-deficient mutant, highlighting the functional significance of PtaT in purine and pyrimidine metabolism. Furthermore, AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and Fn-targeting tsRNA. By uncovering the first RNA-binding protein in Fn implicated in growth modulation through interactions with host-derived small RNAs (sRNAs), our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.
Fusobacterium nucleatum/growth & development* ; RNA-Binding Proteins/genetics* ; Bacterial Proteins/genetics* ; RNA, Bacterial/metabolism* ; Humans ; RNA, Transfer/metabolism*

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

Objective:To explore the clinical efficacy of cenegermin in the treatment of neurotrophic keratitis (NK).Methods:An observational case series study was adopted.Twenty-two patients (26 eyes) with moderate and severe NK diagnosed in Xi'an No.1 Hospital from June to November 2021 were collected and locally treated with cenegermin eye drop.After the corneal epithelium of the affected eye healed, the treatment ended.Relevant index data of patients before and after treatment were obtained through eye examination.The main indicators were the fiber length of corneal sensation measured by Cochet-Bonnet aesthesiometer, the morphological and quantitative indexes of corneal nerves by in vivo confocal microscopy, including the density of corneal nerve fibers and the number of nerve bifurcation points, and tear meniscus height measured by Keratograph Ocular Surface Analyzer.The secondary indicators were best corrected visual acuity (BCVA) and adverse reactions.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xi'an No.1 Hospital (No.2021-11). Written informed consent was obtained from each subject. Results:The average treatment duration of patients receiving cenegermin was (4.42±1.86) weeks.After treatment, the corneal epithelial defect of moderate and severe patients healed completely.After treatment, the fiber length of sensation of corneal epithelial defect area and superior defect area were improved, the differences were statistically significant ( Z=-2.45, -3.22; both at P<0.05). There was no significant difference in corneal sensation in inferior, nasal and temporal of corneal epithelial defect area between before and after treatment ( Z=-1.89, -0.31, -1.86; all at P>0.05). After treatment, the average corneal nerve fiber density and the number of corneal nerve fiber bifurcation points in the affected eyes were significantly increased ( Z=-3.95, -3.48; both at P<0.01). There was no significant difference in the tear meniscus height between before and after treatment ( Z=-1.58, P=0.11). After treatment, the BCVA (LogMAR) of patients was 0.22(0.10, 0.40), which was higher than 0.52(0.30, 0.70) at baseline, and the difference was statistically significant ( Z=-3.63, P<0.01). During the treatment of cenegermin eye drops, transient pain occurred in 3 eyes, and intraocular pressure increased in 1 eye, which all returned to normal after symptomatic treatment. Conclusions:Topical application of cenegermin can repair corneal nerve morphology and function in patients with NK.

2-(4-Methylthiazol-5-yl) ethyl nitrate hydrochloride (W1302) is a nitro containing derivative of clomethiazole, which is a novel neuroprotective agent with both carbon monoxide (NO) donor and weak γ-aminobutyric acid type A (GABA_A) receptor allosteric regulatory excitatory effect. The current study used a rat model of transient middle cerebral arteryocclusion (tMCAO) brain injury to evaluate the therapeutic effect of W1302 on ischemic stroke and explore its potential mechanisms of action. This experiment has been reviewed and approved by the Laboratory Animal Management and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences (ethical review forms No. 620, 632, 5013). The results showed that gavage administration of 1, 3, and 10 mg·kg^-1 of W1302 can significantly reduce the volume of cerebral infarction in rats with ischemia for 2 h and reperfusion for 24 h, and the therapeutic effect was better than that of 200 mg·kg^-1 of DL-3n-butylphthalide. W1302 significantly increased NO levels in blood and brain tissue. It increased cerebral blood flow and brain adenosine triphosphate (ATP) content after reperfusion, as well as, inhibited the expressions of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in brain tissue. The time window of W1302 was between 120-180 min after ischemia. These research results demonstrated that W1302 could increase NO release, dilate blood vessels, and increase cerebral blood flow, improve energy supply to brain tissue and increase ATP levels, and inhibit neuro-inflammation, which playing the protective roles in tMCAO stroke model rats. This provides theoretical support for the clinical application of W1302 in the treatment of ischemic stroke.