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.

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 impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objectives:To explore the therapeutic efficacy of balloon stent kissing technique(BSKT)and jailing wire technique(JWT)in patients with true bifurcation lesions of the left anterior descending branch-diagonal branch of the coronary artery,and to observe the impact of these two interventional procedures on the lumen area,angina symptoms,cardiac function,myocardial injury,and myocardial perfusion of patients.Methods:A retrospective analysis was conducted in 203 patients with true bifurcation lesions of the left anterior descending branch-diagonal branch who underwent BSKT and JWT procedures and completed a 6-month follow-up in the Department of Cardiovascular Medicine at Shijiazhuang People's Hospital from January 2022 to January 2024.Patients were randomly assigned to the BSKT group(n=107)or the JWT group(n=96).The safety,efficacy,and myocardial perfusion indicators of the two groups were compared.Results:The minimum lumen area measured by intravascular ultrasound immediately after procedure,the Canadian Cardiovascular Society angina classification at 6 months post-intervention,the total score of resting+stress myocardial perfusion at 6 months post-intervention,the total number of segments with resting+stress myocardial ischemia,and the abnormal myocardial perfusion area in both the BSKT group and JWT group were significantly improved compared to baseline values(all P<0.05).In the BSKT group,87 cases(81.3%)achieved immediate success in stent placement,whereas in the JWT group,64 cases(66.7%)achieved immediate success in stent placement.The BSKT group significantly outperformed the JWT group.In terms of the myocardial injury and cardiac function indicators assessed on postoperative day 1,the cardiac troponin I level([0.22±0.13]ng/ml vs.[0.45±0.27]ng/ml,P<0.001),creatine kinase MB([35.24±13.15]U/L vs.[42.39±21.66]U/L,P=0.004),and B-type natriuretic peptide([133.52±25.62]pg/ml vs.[167.22±22.04]pg/ml,P<0.001)were all significantly lower in the BSKT group than in the JWT group.In terms of the myocardial perfusion indicators at 6 months post-intervention,the number of ischemic segments under stress(3.23±1.54 vs.3.87±1.62,P=0.004),the total score of stress perfusion(4.18±2.21 vs.4.97±2.96,P=0.031),and the abnormal myocardial perfusion area([7.04±3.27]%vs.[8.24±3.69]%,P=0.014)were all significantly lower in the BSKT group than in the JWT group.Conclusions:Both BSKT and JWT procedures can significantly improve the lumen area of the left anterior descending branch,angina symptoms,and myocardial perfusion in patients with true bifurcation lesions of the left anterior descending branch-diagonal branch.The BSKT procedure provides more adequate protection for the bifurcation vessels compared to the JWT procedure.

Objective:To investigate the status of interdisciplinary training of nursing graduate students and the factors influencing their cognition of interdisciplinary training, and to provide a reference for cultivating innovative nursing talents.Methods:Using the convenient sampling method, an online questionnaire survey was conducted on the Wenjuanxing platform to investigate the current status of multidisciplinary training of nursing graduate students at 6 universities in Chengdu and Chongqing from January to March 2024. SPSS 22.0 software was used for t-test, one-way ANOVA, and multiple linear regression analysis. Results:This study collected 392 valid questionnaires, with 167 (42.60%) respondents reporting engagement in multidisciplinary research. The most common interdisciplinary areas included psychology (70, 41.92%), rehabilitation (59, 35.33%), and elderly care (55, 32.93%). Preferred training methods were research collaboration (341, 86.99%), student exchange or joint training programs (291, 74.23%), and interdisciplinary coursework (261, 66.58%). The main influencing factors for training effectiveness were multidisciplinary mentor team (314, 80.10%), teaching staff (287, 73.21%), and related course learning (278, 70.92%). The challenges in conducting multidisciplinary research included difficulties in acquiring interdisciplinary knowledge (327, 83.42%), high demands for knowledge integration capabilities (284, 72.45%), and a lack of training program (254, 64.80%). Interest in interdisciplinary research, course content involving interdisciplinary studies, and understanding of the interdisciplinary training model were identified as factors influencing the cognition of interdisciplinary training among nursing graduate students ( F=9.42, P<0.001; R2=0.146, adjusted R2=0.131). Conclusions:The multidisciplinary training of nursing graduate students remains in the exploratory stage. Universities should formulate multidisciplinary training programs for nursing graduate students, cultivate their interest in interdisciplinary research, establish cross-disciplinary courses integrating nursing with psychology, rehabilitation, and elderly care, assemble multidisciplinary mentor teams, and support research collaborations or joint training programs. These measures can enhance the comprehensive competencies and innovative capabilities of nursing graduate students.

Objective:To observe the role of impulsivity in cognitive impairment in manic episodes of bipolar Ⅰ disorder(BPDTI)patients.Methods:180 cases of patients with BPDTI manic episodes admitted to our hospital from February 2024 to December 2024 were selected as the manic group,and another 180 cases of volunteers who were psychologically tested as normal during the same period were selected as the healthy group.The impulse Barratt-11 scale(BIS-11)and the MATRICS Consensus Cognitive Test(MCCB)were used to investigate and evaluate impulsivity and cognitive function,and correlation analysis and risk factor analysis were conducted.Results:In the BIS-11 scale,there was no statistically significant difference between the two groups in the unplanned factor(P＞0.05),but there were significant differences compared between the two groups in cognitive,motor factors,and total score(P＜0.05).The MCCB scores of the manic group in information processing speed,working memory,word learning,visual learning,social cognition,reasoning and problem solving,and attention vigilance were significantly lower than those of the healthy group(P＜0.05).The relationship between BIS-11 total score and cognitive impulsivity factor and MCCB total score and word learning showed there were negative correlation(P＜0.05);The exercise factor in the BIS-11 scale were negatively correlated with the MCCB total score and working memory factor(P＜0.05);The unplanned factor in the BIS-11 scale showed there were negative correlation with the MCCB total score,word learning(P＜0.05),and information processing speed.BIS-11,the number of years of education was an influencing factor for BPDTI mania(P＜0.05).Conclusion:BPDTI mania patients had high impulsivity and cognitive impairment,high impulsivity and number of years of education were influencing factors for mania,high impulsivity affected cognitive function through corresponding brain regions,aggravating the condition.

In recent years,the global consumption of ultra-processed foods(UPFs)has increased.UPFs are classified as the fourth group of food in the NOVA classification system:industrially formulated foods made entirely or mostly from substances extracted from foods(oils,fats,sugar,starch,proteins,etc),derivatives of food constituents(hydrogenated fats,modified starches,etc),or multiple food additives.Common manufacturing techniques include extrusion,moulding,and pre-frying.As high-energy-density foods,UPFs are typically characterized by high levels of sugar,fat,and salt,and low levels of dietary fiber,protein,vitamins,and minerals,resulting in low nutrient density.Studies have shown that a high intake of UPFs increases the risk of various chronic diseases.Nutrition during pregnancy is a crucial factor influencing pregnancy outcomes,and balanced and adequate nutrient intake is essential for the health of both the mother and child.Given that UPFs have limited nutritional density,high intake during pregnancy may be detrimental to maternal and infant health.However,the impact of consuming UPFs during pregnancy on maternal and infant health is not extensively studied.This article reviews the literature on the effects of UPFs on pregnancy outcomes,aiming to provide a foundation for further research and personalized dietary guidance.

Objective To investigate the correlation between plasma nucleotide-binding oligomer-ization domain-like receptor protein 3(NLRP3)inflammasome and atrial remodeling in patients with non-valvular atrial fibrillation(NVAF).Methods A total of 199 elderly NVAF patients hos-pitalized in the Department of Cardiology of the First Affiliated Kunming Medical University from July 2019 to October 2020 were enrolled in this study.The levels of inflammatory factors,such as plasma NLRP3 and IL-1β were detected using ELISA.Their clinical data and echocardio-graphic indicators were collected.According to the first quartile of left atrial diameter(LAD),they were divided into a LAD ≤36 mm group(52 cases)and a LAD＞36 mm group(147 cases).Based on the mean level of NLRP3(97 ng/L),the patients were assigned into a low level group(95 ca-ses)and a high level group(104 cases).Using the first quartile of IL-1β at 49 ng/L and the third quartile at 106 ng/L,they were categorized into low,middle and high level groups(40,82 and 77 cases,respectively).The correlation between plasma NLRP3 and IL-1β levels and atrial remode-ling were analyzed.Multivariate logistic regression analysis was conducted to determine whether NLRP3 inflammasome was an independent influencing factor of atrial remodeling in NVAF pa-tients.Results The IL-1β and NLRP3 levels were significantly elevated in the LAD＞36 mm group than the LAD ≤36 mm group(P＜0.05,P＜0.01).The patients with high NLRP3 level had an obviously larger transverse diameter of the middle right atrium than those with low level(P＜0.05).Higher LAD index(LADI)was found in the high IL-1β level group than the low and middle level groups,and larger long diameter of right atrium was observed in the high level group than the low level group(P＜0.05).Plasma NLRP3 level was positively correlated with LAD and transverse diameter of the middle right atrium(r=0.143,P=0.044;r=0.180,P=0.011),and plasma IL-1β level was positively correlated with LAD,LADI,and long diameter of the right atri-um(r=0.153,P=0.031;r=0.148,P=0.037;r=0.142,P=0.046).Multivariate logistic regres-sion analysis indicated that persistent atrial fibrillation,creatinine,pulmonary artery systolic pres-sure,and NLRP3 were independent risk factors for left atrial enlargement(P＜0.05,P＜0.01).Conclusion NLRP3 inflammasome is closely associated with atrial remodeling in elderly NVAF patients,and elevated plasma NLRP3 level is an independent risk factor of left atrial remodeling.

Objective To develop and evaluate a quality assessment system for palliative care nursing homes that integrate medical and elderly care services based on the SERVQUAL model,thereby providing references for assessment and improvement of the quality of palliative care.Methods Using SERVQUAL model,a preliminary evaluation of a quality assessment system for palliative care was developed through literature review and semi-structured interviews.Two rounds of expert consultation with Delphi method were conducted to refine and finalise the assessment system.Results The two rounds of expert consultation each involved 15 questionnaires,all effectively returned(100.00%response rate),reflecting strong expert engagement.The expert authority coefficients were 0.78.The Kendall's W of primary irdicators were 0.198 in the first round to 0.235 in the second(P<0.05),showing improved consensus.The mean importance scores in the second consensus were 3.93-5.00,with coefficients of variation of 0-0.20,and weights of 0.01-0.28,respectively.The finallised assessment system comprised 5 primary indicators,17 secondary indicators and 64 tertiary indicators.Conclusion The SERVQUAL-based palliative care quality assessment system for integrated medical-elderly care nursing homes is scientifically rigorous and practically applicable.It offers a standardised tool for assessment and improvement of the quality of palliative care in nursing homes with integrated medical and elderly care services,promotes homogenisation of nursing quality and ultimately meets the needs of residents and their families.