Objective:To explore the correlation between the expression of fucosylated proteins in colonic epithelium (abbreviated as colonic fucosylation level) and the clinical efficacy of ustekinumab (UST) in patients with Crohn′s disease (CD).Methods:From January 2022 to November 2023, CD patients who were hospitalized at Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University and received the treatment of UST ≥24 weeks (CD group) and patients with colon polyps (colon polyps control group) were retrospectively enrolled. Baseline data of the patients were collected. Harvey-Bradshaw index for Crohn′s disease (HBI) and simple endoscopic score for Crohn′s disease (SES-CD) were applied to assess clinical and endoscopic disease activities, respectively. The colonic fucosylation level was detected by immunofluorescence staining in the CD group at weeks 0 and 24 after UST treatment and at diagnosis in the colon polyps control group (baseline). The levels of C-reactive protein (CRP) and fecal calprotectin (FC) were also assessed. A linear regression model was performed to analyze the correlation between the baseline colonic fucosylation levels and the clinical characteristics in CD patients. At week 24, the clinical efficacy of UST treatment was evaluated, clinical remission was defined as HBI ≤4, biological remission was defined as CRP<5 mg/L and(or) FC≤250 μg/g, and mucosal healing was defined as SES-CD≤2.Based on the efficacy of UST treatment, the CD group was further divided into clinical remission subgroup and clinical non-remission subgroup, biological remission subgroup and biological non-remission subgroup, and mucosal healing subgroup and mucosal non-healing subgroup. The differences in colonic fucosylation level between the subgroups were compared. Multivariate binary logistic regression model was used to analyze the impacts of the baseline clinical characteristics on clinical efficacy at week 24 of UST treatment in the CD group. Mann-Whitney U test and Wilcoxon matched-pair test were used for statistical analysis. Results:A total of 60 patients in the CD group and 72 patients in the colon polyps control group were enrolled. The baseline colonic fucosylation level of CD group was lower than that of the colon polyps control group (25.81 (15.55, 29.70) vs. 29.57 (27.32, 32.96)), and the difference was statistically significant ( Z=-5.02, P<0.001). The results of multiple linear regression analysis showed that the baseline colonic fucosylation level of the CD group was negatively correlated with the baseline FC level ( β=-13.80, 95% confidence interval (95% CI): -20.59 to -7.00, P<0.001). The colonic fucosylation level at week 24 of the CD group was higher than that at week 0 (28.53 (24.54, 32.32) vs. 25.81 (15.55, 29.70)), and the difference was statistically significant ( Z=4.75, P<0.001). The colonic fucosylation levels at week 24 of the clinical remission subgroup, the biological remission subgroup, and the mucosal healing subgroup were higher than those of the clinical non-remission subgroup, the biological non-remission subgroup, and the mucosal non-healing subgroup, respectively (29.1 (27.9, 33.0) vs. 19.6 (16.3, 31.9), 29.5 (27.3, 33.0) vs. 19.6 (17.5, 27.5), 29.6 (28.4, 33.0) vs. 23.4 (17.5, 28.4)), and the differences were statistically significant ( Z=3.35, 3.78, 4.63; all P<0.001). The results of multivariate binary logistic regression analysis showed that the baseline colonic fucosylation level was the independent influencing factor of the rate of clinical remission, biological remission and mucosal healing at week 24 after UST treatment in the CD group ( OR=1.30 (95% CI: 1.05 to 1.61), 1.24 (95% CI: 1.01 to 1.52), 1.57 (95% CI: 1.16 to 2.12); P=0.018, 0.037 and 0.003). Conclusion:The baseline level of colonic fucosylation in CD patients is correlated with the clinical efficacy at week 24 of UST treatment, suggesting its potential utility in predicting the efficacy of UST treatment in CD patients.

In this comprehensive review, we delve into the evolution of drug delivery systems in reproductive medicine with a focus on the emerging role of exosomes, a class of extracellular vesicles. Exosomes offer unique advantages in overcoming these challenges due to their inherent biocompatibility, stability, and ability to facilitate targeted delivery. This review provides a detailed examination of exosome biogenesis and their function in cellular communication, setting the stage for understanding their potential as drug delivery vehicles. We explore the mechanisms through which exosomes can be loaded with small molecule drugs and the benefits they offer over synthetic nanoparticles. The review highlights groundbreaking case studies that illustrate the successful application of exosome-mediated drug delivery in reproductive health, including enhancing fertility treatments, supporting gamete and embryo development, and facilitating maternal-fetal communication. This study aims to provide a precise understanding of how exosomal drug delivery can revolutionize treatments for reproductive health disorders, paving the way for future therapeutic applications. Lastly, we touch upon the promising therapeutic implications of exosomal delivery for proteins and genes, offering a window into future treatments for reproductive health disorders.

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 To investigate the regulatory mechanism of the central nervous system in patients with refractory overactive bladder (rOAB) using diffusion tensor imaging (DTI) and graph theory analysis. Methods A total of 43 rOAB patients (rOAB group) and 46 matched healthy controls (HC group) were recruited during May and Nov.2024. All participants were scanned with DTI, and surveyed with the overactive bladder symptom score (OABSS), and overactive bladder questionnaire (OAB-q). Their age, gender, height, weight, and educational years were collected.DTI plus graph theory analysis was employed to explore the alterations in global and local topological properties of the brain structural network in rOAB patients. Brain regions showing significant group differences in structural metrics [specifically, the right paracentral lobule (PCL.R) ]were further used as seed points for functional connectivity (FC) analysis. Correlations between the nodal clustering coefficient (NCp) of the identified region, FC strength, OABSS, and OAB-q score were investigated. Results The OABSS [8 (6,10) vs.0 (0,1) ]and OAB-q [71 (53,80) vs.20 (19,24) ]were higher in the rOAB group than the HC group (P<0.001). Graph theory analysis revealed no statistically significant differences in global network metrics between the two groups (P>0.05). However, the NCp was significantly higher in the PCL.R of rOAB group compared to HC group (P<0.05, FDR-corrected).FC analysis using the PCL.R as a seed region demonstrated significantly reduced FC value in the left cerebellar crus Ⅱ (Cerebelum_Crus2_L) of the rOAB group (P<0.05, FDR-corrected). Partial correlation analysis showed that the NCp of PCL.R was positively correlated with both OABSS (r=0.255, P=0.018) and OAB-q score (r=0.257, P=0.017). Conversely, the FC of Cerebelum_Crus2_L was significantly negatively correlated with OABSS (r=-0.545, P<0.001) and OAB-q score (r=-0.535, P<0.001). Conclusion Patients with rOAB exhibit distinct brain structural network alterations compared to healthy individuals, primarily manifestation in the NCp value of PCL.R increased, and the FC intensity of Cerebelum_Crus2_L is significantly weakened. These alterations in the topological properties of the structural network may be implicated in the pathogenesis of rOAB.

The study of active substances in traditional Chinese medicine(TCM) is the foundation of TCM pharmacology, TCM quality control, and new drug development, and it is also one of the most popular directions in TCM modernization research in recent years. Due to their diverse chemical compositions and complex component-effect relationships, Chinese medicines often require the comprehensive use of multidisciplinary technologies such as chemistry, biology, and information science to reveal their active substances and targets. In this paper, we review the innovative breakthroughs made in the past 30 years in the discovery strategies and technological means for the research of active substances in traditional Chinese medicine from the perspective of technological changes, and focus on the new direction of the research of active substances in traditional Chinese medicine under the paradigm shift of scientific research brought about by artificial intelligence, with the aim of promoting research in related fields to move in the direction of more accurate, efficient, and intelligent, and providing innovative ideas for the research of active substances in traditional Chinese medicine under the new situation.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Artificial Intelligence ; Drug Discovery/methods* ; Animals

Objective:To explore the pathogenesis,clinical features,treatment strategies,and prognosis of pediatric lymphoepithelioma-like carcinoma(LELC).Methods:A retrospective analysis was conducted on the clinical data of patients with LELC aged<18 years,treated at Sun Yat-sen University Cancer Center from March 2008 to June 2023.Results:A total of 19 children and adolescents were included in the analys-is,comprising 10 males(52.6%)and 9 females(47.4%),with a median age of 12.9(4.3-17.0)years.Fourteen patients(73.7%)lived in Guangdong province,with the remainder scattered across other regions.Primary LELC sites were the mediastinum(11 cases,57.9%),parot-id glands(4 cases,21%),neck(1 case,5.3%),lungs(1 case,5.3%),salivary glands(1 case,5.3%),and submandibular glands(1 case,5.3%).Among these,15 patients(78.9%)had at least one distant metastasis at initial diagnosis,with common metastasis sites being cervical lymph nodes.Multivariate Cox regression analysis identified tumor volume≥801 cm3 as an independent adverse prognostic factor of poor overall survival(OS)(P<0.01).The 2-year OS and progression-free survival(PFS)rates were 84.2%and 57.9%,respectively.The 2-year OS for pa-tients who underwent surgery,chemotherapy,and radiotherapy was 100%,compared with 25%for those who received only partial treat-ment(P=0.007).The 2-year PFS rate was significantly higher in patients receiving first-line combination therapy with programmed death-1(PD-1)antibodies(100%)compared with those not treated with PD-1 antibodies(38.5%)(P=0.020).For patients with tumor volume≥801 cm3,the 2-year OS was 40.0%,whereas for those with a tumor volume<801 cm3,the 2-year OS was 100%(P<0.001).The 2-year OS for pa-tients who underwent radiotherapy was 100%,while it was 0 for those who did not receive radiotherapy(P<0.001).Conclusions:Pediatric LELC exhibits a relatively favorable prognosis with multidisciplinary treatment,including surgery,chemotherapy,and radiotherapy.The com-bined use of PD-1 antibodies at the time of initial diagnosis could offer potential benefits and warrants further exploration.

Objective To construct and assess a training program for newly appointed nurse managers.Methods According to the evaluation index system of nurse manager's post competency,a training team was set up,training experts were selected,and a training program for newly appointed nurse managers was constructed,which was based on the learning pyramid theory,and implemented in 20 newly appointed nurse managers.The scores of post competency scale,core competence scale,team assistance ability scale,and emergency management scale,and the result of practical examination were used as evaluation indexes.Results After half-year training,the mean and four dimension scores of post competency,the mean and six dimension scores of core competence,the mean and four dimension scores of team assistance ability,and the mean and four dimensions scores of emergency management in the 20 newly appointed nurses were significantly higher than those before training(all P<0.05).The mean total score of practical assessment was 92.45±1.81.Conclusion The training program for newly appointed nurse mangers on the basis of the learning pyramid theory can effectively improves the post competence,core competence and practical ability.It can provide theoretical reference for cultivating newly appointed nurse mangers.

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

A 10-year-old girl was admitted with a 38-hour history of widespread subcutaneous petechiae and hematuria and a 6-hour history of jaundice and oliguria. Physical examination revealed widespread subcutaneous petechiae and jaundice of the skin and sclera. Laboratory tests showed anemia, thrombocytopenia, acute kidney injury, and markedly elevated lactate dehydrogenase. Thrombotic microangiopathy was initially diagnosed, with a high suspicion of atypical hemolytic uremic syndrome (aHUS). Eculizumab was initiated within 9 hours of admission (within 48 hours of onset). After the first infusion, hemolysis rapidly ceased, and the platelet count and renal function gradually returned to normal. Whole-exome sequencing identified homozygous deletions of CFHR1 exon 2 and CFHR4 exon 1. aHUS typically has abrupt onset and rapid progression. Clinicians should maintain high suspicion for aHUS when the triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury is present. Ultra-early eculizumab (within 48 hours of onset) rapidly blocks complement-mediated thrombotic microangiopathy, reverses organ injury, and improves long-term prognosis. Additionally, complement-related genetic testing is important for etiological clarification and individualized determination of eculizumab treatment duration.
Humans ; Antibodies, Monoclonal, Humanized/administration & dosage* ; Female ; Atypical Hemolytic Uremic Syndrome/drug therapy* ; Child ; Complement C3b Inactivator Proteins

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers