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.

Attention deficit and hyperactive disorder （ADHD） is the most common neurodevelopmental disorder of childhood. It seriously impairs academic achievement， social interaction， and vocational development， and increases the risk of accidental injury and substance abuse. In some cases， the symptoms may also exert an indirect disruptive effect on public order. Its aetiology involves interactions among genetic， perinatal environmental， and psychosocial factors that cannot be fully disentangled by single clinical studies. Therefore， a systematic evaluation of existing animal models is essential for revealing pathophysiology and developing novel therapies. Using the keywords "attention deficit and hyperactive disorder"， "models， animal"， "validity"， and their English equivalents， we systematically searched PubMed， Web of Science， CNKI， and Wanfang for publications from 2000 to 2025 （retrieving 328 publications） and added further references by citation tracking. Eighty-six rodent ADHD models that provided detailed construction protocols， behavioural assessments， neurobiological mechanisms， or pharmacological data were included and classified into spontaneous genetic， genetically engineered， and environmentally induced paradigms. Their face， construct， and predictive validity were compared. Among spontaneous genetic models， spontaneously hypertensive rats reproduce hyperactivity， impulsivity， and stimulant responses well， yet hypertension and sex differences limit specificity. Acallosal mouse strains link corpus callosum absence to ADHD-like behaviours， but neurotransmitter studies remain scarce. Genetically engineered rodents—including dopamine transporter， neurokinin-1 receptor and mediator complex subunit 23 knockout or conditional gene knockout lines—precisely dissect dopaminergic， noradrenergic， synaptic， or epigenetic pathways， yet generally lack full phenotypic coverage， social-deficit modelling， and comorbidity representation， and are accompanied by adverse effects such as growth retardation or ocular defects. Environmentally induced models employ lead， polychlorinated biphenyls， alcohol， nicotine exposures， 6-hydroxydopamine lesions， neonatal hypoxia， early social isolation， or maternal stress to recapitulate core symptoms. However， dose-schedule standardisation is lacking. Behavioural reversibility diverges from clinical persistence， and non-specific phenotypes such as anxiety or depression are common. Overall， no single paradigm simultaneously achieves high validity across all three dimensions. Currently， ADHD models have progressed from single-factor simulations to multidimensional evaluation， yet significant gaps remain in genetic-background standardisation， sex differences， cross-species translation， and syndrome-differentiation modelling under traditional Chinese medicine. Future directions should integrate genetic， environmental， and epigenetic interactions， establish life-span validation systems， and incorporate computational neuroscience alongside integrative Chinese-Western strategies to enhance clinical relevance and translational utility， thereby providing robust evidence-based support for mechanistic elucidation， drug screening and precision intervention in ADHD.

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.

Polycystic ovary syndrome （PCOS） is one of the most prevalent gynecological diseases， and its incidence is increasing year by year， seriously affecting the physical and mental health of female patients. The pathogenesis of this disease is complex and has not been fully clarified. At present， PCOS is mainly treated by Western medicine， which， however， has poor efficacy and induces various adverse reactions. Therefore， developing safe and effective therapies has become a difficult problem that needs to be solved. Studies have confirmed that traditional Chinese medicine （TCM） can regulate phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， mitogen-activated protein kinase/extracellular signal-regulated kinase （MAPK/ERK）， Toll-like receptor 4/nuclear factor-κB （TLR4/NF-κB）， transforming growth factor-β （TGF-β）/Smads， secreted glycoprotein/β-catenin （Wnt/β-catenin）， adenosine monophosphate-activated protein kinase （AMPK）， and advanced glycation endproduct/receptor for advanced glycation endproducts （AGE/RAGE） signaling pathways to ameliorate insulin resistance， inhibit inflammation and oxidative stress， regulate endocrine hormone disorders， and intervene in apoptosis and autophagy， thus alleviating the symptoms， slowing down the disease progression， and improving the ovarian function. The treatment of PCOS with TCM has demonstrated definite effects and high safety. Therefore， exploring this disease from cellular and molecular perspectives can provide a theoretical basis for its clinical treatment and new drug development. However， there is a lack of systematic reviews on the modulation of relevant signaling pathways by TCM in the treatment of PCOS. This article reviews the research progress in the treatment of PCOS with the active ingredients and compound prescriptions of TCM by regulating relevant signaling pathways in recent years， with the aim of providing evidence to support the promotion of TCM for treating PCOS in the future.

Objective To evaluate the effect of laparoscopic surgery on incarcerated inguinal hernia(IIH)in children.Methods A total of 81 IIH children treated at Jinhua Maternal & Child Health Hospital from September 2018 to December 2023 were selected as subjects.The children were divided into laparoscopic surgery group(n=45)and open surgery group(n=36).Comparative analysis was conducted on admission age,gender,duration of incarceration,surgical timing,intraoperative hernia contents,and postoperative complications between two groups.Results Operative duration,intraoperative blood loss,postoperative bowel function recovery time,number of occult hernias,and hospitalization duration in laparoscopic surgery group were statistically better than those in open surgery group(P＜0.05).There were fewer postoperative complications in laparoscopic group compared to open surgery group,there was significant difference between two groups(P＜0.05).Conclusion Compared with traditional open surgery,laparoscopic surgery for IIH in children has the advantages of less trauma,shorter operation time and hospitalization time,and less intraoperative bleeding.

Objective:To analyze the evolution of ceftazidime/avibactam (CZA) resistance phenotyes and clinical features of 11 ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates carrying bla KPC. Methods:Eleven CRKP isolates, designated K01 to K11, obtained from infected liver transplant patients from June to September 2024 were retrospectively studied. Broth microdilution method, whole genome sequencing (WGS) and plasmid conjugation assays were employed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural characteristics of these CRKP isolates. Clinical data were simultaneously collected and organized to analyze the correlation between bla KPC gene mutations and the clinical efficacy of antimicrobial therapy. Results:All eleven isolates of CRKP exhibited multidrug resistance phenotypes. Among them, K01-K09 and K11 were sensitive to CZA and resistant to carbapenems, while K10 was resistant to CZA and displayed sensitivity or intermediate resistance to carbapenems. WGS analysis showed that all 11 CRKP isolates belonged to the ST11-KL64 clonal type. Among these isolates, the K01-K09 and K11 isolates carry the bla KPC-2 gene, whereas the K10 isolate carries the bla KPC-33 gene. A single nucleotide mutation in bla KPC-2 (G532T) resulted in a substitution of tyrosine (Y) for aspartic acid (D) at Ambler position 179 (D179Y), causing resistance of CRKP to CZA and reduced sensitivity to Imipenem and Meropenem. The conjugative plasmid was successfully constructed, and compared to the parental strain, its minimum inhibitory concentration (MIC) to CZA increased 32 folds. Clinical data revealed that the patient developed the bla KPC-33 mutation after 51 days of CZA treatment. Conclusions:The bla KPC-33 mutation following CZA treatment for CRKP infection exhibits a considerable delay. It is essential to dynamically monitor the evolution of CRKP resistance to ensure timely adjustment of therapeutic strategies in case of the occurrence of mutations such as bla KPC-33.

Objective Based on multi-dimensional bioinformatics technology,the molecular pathological mechanism of acute hypotension is systematically analyzed.Methods Integrate the gene expression profile of the Gene Expression Omnibus database(GSE2401),use limma package(R software)to screen differential genes,and optimize targets through data dimensionality reduction(log2(FC)＞1,P＜0.05);Further combine Gene Ontology,Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis pathway enrichment and STRING-Cytoscape(MCODE,CytoHubba plug-in)to build a protein-protein interaction(PPI)network to mine core genes;realize the full-chain analysis of"differential gene-functional pathway-PPI network".Results 676 differential genes(304 upregulated,372 downregulated),ribosome structural components(Rps8,Rps27,Rpl35,etc.)and multiple pathways such as forkhead box protein and cyclic adenosine monophosphate were found to coordinate the regulation of acute hypotension.Conclusion This study uses a low-cost and efficient bioinformatics analysis framework to reveal the association between ribosomal dysfunction,changes in insulin signal efficacy and blood pressure regulation,providing new ideas for targeted therapy.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

OBJECTIVE: To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2). METHODS: Three children who were diagnosed with ILFS2 at the Children's Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). RESULTS: The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c.3596G>A and c.1181A>T in child 1, c.2617C>T and c.2T>C in child 2, and c.3596G>A and c.2817_2818insT in child 3. Among these, the c.1181A>T and c.2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+PM3+PP3) and pathogenic (PVS1+PM2_Supporting+PM3). CONCLUSION Combined with the patient's clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c.1181A>T and c.2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.
Humans ; Exome Sequencing ; Genetic Testing/methods* ; Liver Failure, Acute/etiology* ; Mutation ; Child ; Adult ; Neoplasm Proteins

Objective: To investigate the sleep quality in patients with burning mouth syndrome (BMS) and its influencing factors, providing a basis for developing sleep intervention measures to reduce the impact of BMS symptoms. Methods: This study was reviewed and approved by the Medical Ethics Committee, and informed consent was obtained from patients. A total of 150 patients with BMS and 150 healthy volunteers were enrolled as subjects in this study. The Pittsburgh sleep quality index (PSQI) was used to assess the sleep quality of patients with BMS. Visual analog scale (VAS) was used to assess the degree of oral mucosal pain, generalized anxiety disorder 7-item scale (GAD-7) was used to assess the frequency of anxiety symptoms, and the patient health questionnaire depression questionnaire (PHQ-9) was used to assess the frequency of depression symptoms. Univariate analysis was performed to identify potential influencing factors affecting sleep quality in patients with BMS, and multiple linear regression analysis was employed to determine independent risk factors. Results: The PSQI score for patients with BMS was 7.61 ± 4.29, which was significantly higher than that of healthy controls (P = 0.016). In the PSQI subscale analysis, patients with BMS exhibited increased sleep latency, decreased sleep duration, and lower sleep efficiency compared to healthy controls (P<0.05). Patients with BMS and comorbid sleep difficulties had significantly higher scores on GAD-7 and PHQ-9 compared to the patients with BMS without sleep difficulties (P<0.001), but there was no significant difference in pain VAS scores between the two (P = 0.068). Multiple linear regression analysis revealed that longer disease duration (>6 months), the presence of systemic concomitant symptoms (such as headache and mental stress), and higher depression scores were identified as independent risk factors affecting sleep quality in patients with BMS. Conclusion For patients with BMS, long course of illness, presence of headaches, high mental stress, and depressive symptoms may be independent factors affecting their sleep quality.