Objective: To identify research priorities on physical and mental comorbidity among children and adolescents in Zhejiang Province, so as to provide a theoretical base for improving their physical and mental health. Methods: In May 2025, 77 experts in the fields of health and education from 11 cities in Zhejiang Province were selected by convenient sampling method to participate in the first round of expert consultation. In June, 2025, snowball sampling was used to expand to 194 experts for the second round of consultation, and it was convenient to select 21 students from primary schools to high schools in Zhejiang Province and 29 parents to empower the evaluation criteria. It applied the Child Health and Nutrition Research Initiative (CHNRI) method in a structured process, which encompassed the definition of the research field, generation of research ideas, scoring, and quantitative ranking of priorities. Research ideas were evaluated against 6 predefined criteria: effectiveness, safety, answerability, feasibility, sustainability, and scientific significance. Results: After 2 rounds of structured consultations, 81 research ideas on physical and mental comorbidity among children and adolescents were established and classified into 7 subthemes: epidemiological characteristics and influencing factors, optimization of primary service systems and policies, comprehensive intervention strategies for physical and mental comorbidity, biological mechanisms and clinical research, the impact of education and environment on physical and mental health, special populations and social support, and digital and technology driven disease prevention and intervention. The top 10 research priorities primarily centered on the subdomain of "epidemiological characteristics and influencing factors" (5 items). The top 3 research priorities were "the association between outdoor activity duration and the incidence of common diseases (including mental disorders) among children and adolescents" "the impact of outdoor activity duration on the physical and mental health of adolescents" "comprehensive intervention strategies for myopia, obesity, and their comorbidities among children and adolescents". Conclusion The framework of priority issues in the field of psychosomatic comorbidity of children and adolescents in Zhejiang Province based on CHNRI method provides a reference for optimizing the allocation of provincial research resources.

ObjectiveTaking Aurantii Fructus Immaturus juice（AFI）-processed Atractylodis Macrocephalae Rhizoma（AMR） as an example， this study aims to systematically compare the volatile and non-volatile components of AMR and its processed products， investigate the key differential components， evaluate their anti-inflammatory activities， and elucidate the synergistic mechanism of processing. MethodsThe chemical compositions of volatile and non-volatile components in AMR and AFI-processed AMR were systematically characterized using gas chromatography-mass spectrometry（GC-MS） and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， with relative mass fractions and response values determined separately. Volatile components were identified through searches in the National Institute of Standards and Technology（NIST）17 database， comparison with retention index（RI） and fragmentation pattern matching. Non-volatile components were identified by searching Waters Traditional Chinese Medicine （TCM） spectral library， in conjunction with PubChem and MassBank， characteristic fragmentation patterns and response values were also used to support identification. Differential components were screened using principal component analysis（PCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） value >1. Components with high log₂fold change（FC） among major differential groups were selected as those exhibiting significant changes before and after processing. The anti-inflammatory activity of the differential compounds was evaluated by assessing their effects on nitric oxide（NO） production in a lipopolysaccharide（LPS）-induced RAW264.7 macrophage model. Enzyme-linked immunosorbent assay（ELISA） was used to detect the effects of the differential components on tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6， and monocyte chemotactic protein（MCP）-1 levels， and immunofluorescence（IF） was employed to assess their effects on nuclear transcription factor（NF）-κB p65 translocation， thereby elucidating the underlying molecular mechanisms. ResultsA total of 36 compounds were identified in the volatile components of AMR and AFI-processed AMR， among which， sesquiterpenes and monoterpenes were significantly increased after processing. In the non-volatile components， 36 compounds were identified， and the main differential components were flavonoids， sesquiterpenoids， and triterpenoids. Flavonoids were the primary differential components distinguishing AMR from its processed products， representing compounds directly introduced during processing. Five compounds， including atractylenolide Ⅲ， tangeritin， nobiletin， hesperidin and narirutin， were selected as representatives of three classes based on their most prominent differential expression among different compound types for subsequent anti-inflammatory activity studies. The results showed that 100 μmol·L^-1 tangerine and narirutin could significantly inhibit LPS-induced NO production（P<0.01） in a concentration-dependent manner. Tangeritin was able to significantly inhibit the levels of TNF-α and MCP-1 secreted by RAW264.7（P<0.05）， while narirutin significantly inhibited the levels of TNF-α， IL-1β， MCP-1 and IL-6（P<0.01）. IF revealed that both tangeritin and narirutin significantly blocked the translocation of NF-κB p65 from the cytoplasm to the nucleus. ConclusionAFI-processed AMR significantly alters the chemical composition profile of AMR， and the newly introduced flavonoid components during processing may be key to its enhanced anti-inflammatory effects.

The linear ubiquitin chain assembly complex (LUBAC), composed of heme-oxidized IRP2 ubiquitin ligase 1-interacting protein (HOIP), haem-oxidized IRP2 ubiquitin ligase-1(HOIL-1), and SHANK-associated RBCK1 homology-domain-interacting protein (SHARPIN), and its specific deubiquitinating enzyme OTULIN, regulates the dynamic balance of Met1-linked linear ubiquitination and maintains ubiquitin signaling homeostasis. Their precise interaction plays a central role in the regulation of nuclear factor-κB (NF-κB) and type I interferon signaling, inflammatory response, and cell survival and death. Dysregulation of the LUBAC-OTULIN axis can lead to aberrant immune and inflammatory signaling, immunodeficiency, and dysregulation of receptor-interacting protein kinase 1-mediated apoptosis or necroptosis. Genetic defects in OTULIN and LUBAC are associated with rare autoinflammatory diseases such as OTULIN-related autoinflammatory syndrome (ORAS) and HOIP/HOIL-1/SHARPIN deficiency, respectively, with complex clinical phenotypes and gene dose correlation. Current treatments primarily rely on glucocorticoids and tumor necrosis factor inhibitors, and hematopoietic stem cell transplantation has shown potential curative value in some patients with severe ORAS. This review summarizes the molecular composition, interaction mechanisms, and pathogenic roles of the LUBAC-OTULIN axis in rare autoinflammatory diseases, providing reference for the development of targeted therapeutic strategies.

With the rapid advancement of medical technology and the increasing complexity of clinical environments, competence in clinical ethical decision-making has become an indispensable core competency for exemplary physicians. However, traditional medical ethics education has long been confronted with the persistent challenges of theory-practice dissociation and the disconnect between pedagogical settings and clinical realities. Thus, how to construct a "Clinical Ethics" curriculum that aligns with the objectives of training high-caliber medical professionals has emerged as a critical and challenging issue in current medical education reform. To effectively address this challenge, the Office of Education at Peking University Third Hospital, since 2021, has assembled a multidisciplinary "Clinical Ethics" teaching and management team comprising faculty from Peking University School of Humanities and key clinical specialists from the hospital. In 2022, the "Clinical Ethics" elective course was formally launched for fourth-year students in the eight-year MD program who had completed coursework in "Medical Ethics" and organ-system-based curricula, with the aim of exploring and operationalizing a pre-clinical ethics education model tailored for senior medical students. The course employs a modular instructional design encompassing "theoretical review-case-based deliberation-clinical workshop", which effectively facilitates the deep integration of medical humanities with clinical practice.Following four years of iterative refinement through the "plan-act-observe-reflect" cycle, the course has demonstrated positive outcomes in enhancing students' ethical awareness and decision-making capabilities, and has preliminarily established a sustainable collaborative mechanism among the multidisciplinary faculty team. This article systematically delineates the course development background, pedagogical model and methodological innovations, and the multidisciplinary collaborative framework, alongside reflections and summaries based on implementation outcomes, with the intent of providing references for the future development of "Clinical Ethics" curricula.

Clonal cell abnormalities represent a shared initiating event for systemic inflammation and organ injury across a spectrum of diseases, with diverse clonal origing including somatic mutations, germline mutations, and aberrant monoclonal immunoglobulin secretion. This review focuses on the clinical features, mechanism studies and therapeutic advances of the diseases, including VEXAS (vacuoles, E1 enzyme, X-linked, autoin-flammatory, somatic) syndrome, GATA2 deficiency, STAT3 gain-of-function (STAT3-GOF)syndrome, secondary hemophagocytic lymphohistiocytosis, and Schnitzler syndrome. It aims to deepen clinical understanding of these diseases and provide references for precision treatment.

Objective To identify the enhancer profile marked by histone H3K27ac modification in high-grade intraepithelial neoplasia(HGIN)in order to reveal the novel regulatory mechanism of HGIN pathogensis.Methods Gastric tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA between June 2022 and June 2023,including 14 normal gastric tissues(Nor group),31 HGIN tissues(HGIN group)and 17 gastric cancer tissues(GC group).Cleavage under targets and tagmentation(CUT&Tag)technique was employed to capture enhancer regions modified by histone H3K27ac.Multi-omics analysis was performed to identify HGIN-specific active enhancers and their potentially regulated genes.Immunohistochemical profiling was performed to assess differential expression of the gene of interest across clinically stratified specimens,combined with CRISPR-dCas9-mediated ablation of active enhancers to monitor the gene of interest transcriptional dynamics and validate enhancer-mediated regulatory mechanisms.Results Epigenomic sequencing obtained the data with excellent quality,and indicated that obvious remodeling was observed in H3K27ac enhancers in HGIN and GC groups(P<0.05),though no significant difference in the genome-wide distribution of H3K27ac modification among the 3 groups.Combining transcriptome data revealed that enhancer remodeling may up-regulate the expression of the proliferation-related target gene,CD24,in the HGIN tissue;while,inhibiting enhancer activity can notably reduce CD24 expression level(P<0.05).Immunohistochemical assay displayed a positive correlation between the expression levels of CD24 and Ki-67(P<0.001).Conclusion The remodeling of H3K27ac enhancer represents a significant epigenetic feature of the transformation from normal condition to HGIN.Remodeling of H3K27ac enhancer up-regulates CD24,which may facilitate the abnormal proliferation of gastric epithelial cells.

To analyze the prevalence, drug resistance and whole genome characteristics of Mycoplasma pneumoniae (MP) in respiratory throat swab samples of hospitalized children with pneumonia in Suzhou City from 2023 to 2024. Throat swab samples of hospitalized children aged 0-14 years old with pneumonia in Suzhou were collected from September 2023 to September 2024. Real-time fluorenscence quantitative PCR technology was used to detect MP nucleic acid. The results showed that the positive rate of MP in 3 235 samples was 22.44% (726/3 235), with a rate of 55.00% in week 47 of 2023. The positive rate of MP increased with age ( χ2=45.842, P<0.001). The study selected MP nucleic acid test positive samples from week 20 (5.13-5.19) to week 23 (6.3-6.9) of 2024 for isolation, culture and resistance phenotype detection. About 31 MP strains were successfully isolated and cultured, all of which were resistant to macrolides. The next-generation sequencing technology and nanopore sequencing technology were used for genome sequencing. All 31 strains carried the A2063G mutation, with the main prevalent genotype being the P1-1, and the main mlST type being the ST3. Despite the overall genomic similarity between strains being over 99%, there were significant differences between the P1-1 and P1-2 strains in the P1 gene region. In summary, from 2023 to 2024, the main MP type prevalent in Suzhou City is the P1-1 genotype. All isolated MP strains carry an A2063G resistance site mutation and are resistant to macrolides, requiring continuous monitoring and further research.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Objective:To explore the potential category characteristics of social participation in colorectal cancer patients with stoma and analyze the influencing factors of different potential categories, so as to provide references for formulating and implementing targeted nursing measures.Methods:By using the convenience sampling method, colorectal cancer patients with stoma who were hospitalized or had outpatient follow-up visits at Guilin Hospital of Integrated Traditional Chinese and Western Medicine and the Second Affiliated Hospital of Guilin Medical University from January to December 2024 were selected as the survey subjects. A cross-sectional survey was conducted using the general information questionnaire, the voluntary participation Questionnaire, the Existential Anxiety Scale, the Family Support Scale and the Social Support Rating Scale. Potential profile analysis was used to identify the categories of social participation characteristics of colorectal cancer stoma patients, and multivariate Logistic regression was used to analyze the related influencing factors.Results:A total of 240 valid questionnaires were finally retrieved. Among the 240 colorectal cancer patients with stoma, 126 were male and 114 were female, aged 34-75 (55.63 ± 6.52) years. The social participation score of colorectal cancer patients with stoma was (55.84 ± 8.62) points. The results of potential profile analysis showed that the social participation of colorectal cancer patients with stoma could be divided into three potential categories: low participation-inefficient social life type accounted for 38.3% (92/240), medium participation-efficient indoor participation type accounted for 36.3% (87/240), and high participation-efficient outdoor participation type accounted for 25.4% (61/240). The results of multivariate Logistic regression analysis showed that, taking the high participation-efficient outdoor participation type as the reference, age, educational level, presence absence of stoma-related complications, existence of meaningless anxiety, family support, and social support were the influencing factors of low participation-inefficient social life type and medium participation-efficient indoor participation type ( OR values ranged from 0.163 to 1.879, all P<0.05). Conclusions:There are obvious classification characteristics in the social participation of colorectal cancer patients with stoma. Nursing staff can formulate and implement targeted intervention strategies based on different classification characteristics. Starting from the existence of meaningless anxiety in patients, an effective family and social support system should be established to improve their social participation.